Trial Outcomes & Findings for Phase 1/2 Study of USL311 +/- Lomustine in Advanced Solid Tumors or Relapsed/Recurrent Glioblastoma Multiforme (GBM) (NCT NCT02765165)

Last Updated: 2021-07-23

Results Overview

The MTD was defined as the highest safe dose (mg/m\^2) administered where safe is defined by having at least a 50% probability that the dose limiting toxicity (DLT) rate is less than 33%, as determined by a modified continuous reassessment model.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

26 participants

Primary outcome timeframe

Assessed weekly during treatment period. Median duration of exposure was 5.14 (range 2.1-17.3) weeks.

Results posted on

2021-07-23

Participant Flow

Enrolled subjects participated in only one part (parts 1, 2, 3 or 4) of the study. Due to early termination of the study, no subjects were enrolled in parts 2, 3 or 4.

Participant milestones

Participant milestones
Measure	Part 1a, Cohort 1 USL311, intravenous, once per week, 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 USL311, intravenous, once per week, 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3 USL311, intravenous, once per week, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 USL311, intravenous, once per week, 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 USL311, oral, once per day, 160 mg, in 21-day cycles
Treatment Period STARTED	3	4	3	3	6	3	4
Treatment Period COMPLETED	0	0	0	0	0	0	0
Treatment Period NOT COMPLETED	3	4	3	3	6	3	4
Post-treatment Follow-up STARTED	1	3	3	3	3	3	1
Post-treatment Follow-up COMPLETED	0	0	0	0	0	0	0
Post-treatment Follow-up NOT COMPLETED	1	3	3	3	3	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1a, Cohort 1 USL311, intravenous, once per week, 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 USL311, intravenous, once per week, 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3 USL311, intravenous, once per week, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 USL311, intravenous, once per week, 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 USL311, oral, once per day, 160 mg, in 21-day cycles
Treatment Period Progressive disease	3	2	3	3	4	2	2
Treatment Period Physician Decision	0	1	0	0	0	0	0
Treatment Period Adverse Event	0	1	0	0	0	0	0
Treatment Period Withdrawal by Subject	0	0	0	0	2	0	0
Treatment Period Study terminated	0	0	0	0	0	1	2
Post-treatment Follow-up Death	1	2	1	1	1	1	0
Post-treatment Follow-up Lost to Follow-up	0	0	0	1	0	0	0
Post-treatment Follow-up Site terminated by sponsor	0	0	1	0	0	0	0
Post-treatment Follow-up Initiation of subsequent treatment	0	0	1	1	0	0	0
Post-treatment Follow-up Withdrawal by Subject	0	1	0	0	0	0	0
Post-treatment Follow-up Study terminated by the sponsor	0	0	0	0	2	2	1

Baseline Characteristics

Phase 1/2 Study of USL311 +/- Lomustine in Advanced Solid Tumors or Relapsed/Recurrent Glioblastoma Multiforme (GBM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1a, Cohort 1 n=3 Participants USL311, intravenous, once per week, 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 n=4 Participants USL311, intravenous, once per week, 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3, n=3 Participants USL311, intravenous, once per week, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4, n=3 Participants USL311, intravenous, once per week, 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 n=6 Participants USL311, oral, daily, 40 mg, in 21-day cycles	Part 1b, Cohort 2 n=3 Participants USL311, oral, daily, 80 mg, in 21-day cycles	Part 1b, Cohort 3 n=4 Participants USL311, oral, daily, 160 mg, in 21-day cycles	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=99 Participants	3 Participants n=107 Participants	2 Participants n=206 Participants	2 Participants n=7 Participants	3 Participants n=31 Participants	1 Participants n=30 Participants	3 Participants n=3 Participants	17 Participants n=6 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	3 Participants n=31 Participants	2 Participants n=30 Participants	1 Participants n=3 Participants	9 Participants n=6 Participants
Age, Continuous	46.7 years STANDARD_DEVIATION 24.83 • n=99 Participants	53.5 years STANDARD_DEVIATION 16.20 • n=107 Participants	57.7 years STANDARD_DEVIATION 17.79 • n=206 Participants	60.3 years STANDARD_DEVIATION 10.97 • n=7 Participants	62.5 years STANDARD_DEVIATION 14.60 • n=31 Participants	72.0 years STANDARD_DEVIATION 9.17 • n=30 Participants	57.3 years STANDARD_DEVIATION 6.95 • n=3 Participants	58.8 years STANDARD_DEVIATION 14.77 • n=6 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	2 Participants n=107 Participants	0 Participants n=206 Participants	3 Participants n=7 Participants	3 Participants n=31 Participants	2 Participants n=30 Participants	1 Participants n=3 Participants	12 Participants n=6 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants	0 Participants n=7 Participants	3 Participants n=31 Participants	1 Participants n=30 Participants	3 Participants n=3 Participants	14 Participants n=6 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants	0 Participants n=3 Participants	4 Participants n=6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants	2 Participants n=7 Participants	5 Participants n=31 Participants	2 Participants n=30 Participants	4 Participants n=3 Participants	22 Participants n=6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	1 Participants n=6 Participants
Race (NIH/OMB) White	3 Participants n=99 Participants	4 Participants n=107 Participants	2 Participants n=206 Participants	2 Participants n=7 Participants	6 Participants n=31 Participants	3 Participants n=30 Participants	3 Participants n=3 Participants	23 Participants n=6 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	1 Participants n=6 Participants
Region of Enrollment United States	3 participants n=99 Participants	4 participants n=107 Participants	2 participants n=206 Participants	3 participants n=7 Participants	6 participants n=31 Participants	3 participants n=30 Participants	4 participants n=3 Participants	25 participants n=6 Participants
Region of Enrollment Spain	0 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants	0 participants n=7 Participants	0 participants n=31 Participants	0 participants n=30 Participants	0 participants n=3 Participants	1 participants n=6 Participants
Body surface area	1.767 m^2 STANDARD_DEVIATION 0.0503 • n=99 Participants	2.018 m^2 STANDARD_DEVIATION 0.3363 • n=107 Participants	2.000 m^2 STANDARD_DEVIATION 0.2307 • n=206 Participants	1.787 m^2 STANDARD_DEVIATION 0.1704 • n=7 Participants	1.910 m^2 STANDARD_DEVIATION 0.3864 • n=31 Participants	1.820 m^2 STANDARD_DEVIATION 0.0624 • n=30 Participants	2.088 m^2 STANDARD_DEVIATION 0.1893 • n=3 Participants	1.923 m^2 STANDARD_DEVIATION 0.2603 • n=6 Participants

PRIMARY outcome

Timeframe: Assessed weekly during treatment period. Median duration of exposure was 5.14 (range 2.1-17.3) weeks.

Outcome measures

Outcome measures
Measure	Part 1a, Dose-escalation, All Oral Cohorts n=13 Participants USL311, intravenous, once per week, starting at 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 USL311, intravenous, once per week over 2 hours, 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3a USL311, intravenous, once per week over 2 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3b USL311, intravenous, once per week over 4 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 USL311, intravenous, once per week over 4 hours, 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 USL311, oral, once per day, 160 mg, in 21-day cycles
Phase 1: Maximum Tolerated Dose (MTD)	NA mg/m^2 An MTD was not determined for Part 1a due to early termination of intravenous dosing and change to oral dosing	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Assessed weekly during treatment period. Median duration of exposure was 6.00 (range 0.3-30.0) weeks.

The MTD was defined as the highest safe dose (mg) administered where safe is defined by having at least a 50% probability that the dose limiting toxicity (DLT) rate is less than 33%, as determined by a modified continuous reassessment model.

Outcome measures

Outcome measures
Measure	Part 1a, Dose-escalation, All Oral Cohorts n=13 Participants USL311, intravenous, once per week, starting at 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 USL311, intravenous, once per week over 2 hours, 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3a USL311, intravenous, once per week over 2 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3b USL311, intravenous, once per week over 4 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 USL311, intravenous, once per week over 4 hours, 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 USL311, oral, once per day, 160 mg, in 21-day cycles
Phase 1: Maximum Tolerated Dose (MTD)	NA mg An MTD was not determined in Part 1b due to study termination	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Once every 6 weeks during treatment

Population: Due to early termination of study in Phase 1, efficacy outcomes, including PFS-6m, were not analyzed for subjects in Part 1a or Part 1b. Therefore no subjects were included in this analysis population.

Percentage of subjects who were without progression at 6 months as assessed radiographically with response to treatment determined by Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO) criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weekly during treatment or every 12 weeks during follow-up

Population: Due to early termination of study in Phase 1, efficacy outcomes, including OS, were not analyzed for subjects in Part 1a or Part 1b. Therefore no subjects were included in this analysis population.

Percentage of subjects alive five years after start of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 6 weeks during treatment

Population: Due to early termination of study in Phase 1, efficacy outcomes, including median PFS, were not analyzed for subjects in Part 1a or Part 1b. Therefore no subjects were included in this analysis population.

Time after initiation of treatment before disease progression

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 6 weeks

Population: Number of participants changed to 0 and explanation modified to "Due to early termination of study in Phase 1, efficacy outcomes, including ORR% were not analyzed for subjects in Part 1a or Part 1b. Therefore no subjects were included in this analysis population.

Percentage of patients whose disease decreased (Partial response) and/or disappears (Complete response) after initiation of treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1

Population: Subjects who received scheduled dose and had sufficient PK samples for determination of parameters

Peak USL311 concentration (Cmax) in plasma

Outcome measures

Outcome measures
Measure	Part 1a, Dose-escalation, All Oral Cohorts n=3 Participants USL311, intravenous, once per week, starting at 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 n=4 Participants USL311, intravenous, once per week over 2 hours, 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3a n=1 Participants USL311, intravenous, once per week over 2 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3b n=2 Participants USL311, intravenous, once per week over 4 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 n=2 Participants USL311, intravenous, once per week over 4 hours, 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 n=5 Participants USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 n=3 Participants USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 n=4 Participants USL311, oral, once per day, 160 mg, in 21-day cycles
Peak Concentration (Cmax)	48.2 ng/mL Geometric Coefficient of Variation 41.1	69.1 ng/mL Geometric Coefficient of Variation 66.9	200 ng/mL Geometric Coefficient of Variation NA CV% not calculable as 1 subject	168 ng/mL Geometric Coefficient of Variation 94	107 ng/mL Geometric Coefficient of Variation 37.2	2.06 ng/mL Geometric Coefficient of Variation 84.6	4.74 ng/mL Geometric Coefficient of Variation 32.4	6.68 ng/mL Geometric Coefficient of Variation 58.5

SECONDARY outcome

Timeframe: Day 1

Population: Subjects who received scheduled dose and had sufficient PK samples for determination of parameters

Time to peak concentration of USL311 in plasma

Outcome measures

Outcome measures
Measure	Part 1a, Dose-escalation, All Oral Cohorts n=3 Participants USL311, intravenous, once per week, starting at 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 n=4 Participants USL311, intravenous, once per week over 2 hours, 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3a n=1 Participants USL311, intravenous, once per week over 2 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3b n=2 Participants USL311, intravenous, once per week over 4 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 n=2 Participants USL311, intravenous, once per week over 4 hours, 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 n=5 Participants USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 n=3 Participants USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 n=4 Participants USL311, oral, once per day, 160 mg, in 21-day cycles
Time to Peak Concentration (Tmax)	1.05 Hours Interval 1.02 to 2.03	1.04 Hours Interval 1.02 to 2.03	0.53 Hours Interval 0.53 to 0.53	2.28 Hours Interval 0.5 to 4.05	2.55 Hours Interval 2.05 to 3.05	0.63 Hours Interval 0.48 to 2.0	0.67 Hours Interval 0.53 to 1.0	0.565 Hours Interval 0.52 to 0.98

SECONDARY outcome

Timeframe: Day 1

Population: Subjects who received scheduled dose and had sufficient PK samples for determination of parameters

Area under the curve versus time from time 0 to infinity for USL311 concentration in plasma

Outcome measures

Outcome measures
Measure	Part 1a, Dose-escalation, All Oral Cohorts n=3 Participants USL311, intravenous, once per week, starting at 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 n=4 Participants USL311, intravenous, once per week over 2 hours, 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3a n=1 Participants USL311, intravenous, once per week over 2 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3b n=2 Participants USL311, intravenous, once per week over 4 hours, 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 n=2 Participants USL311, intravenous, once per week over 4 hours, 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 n=5 Participants USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 n=3 Participants USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 n=4 Participants USL311, oral, once per day, 160 mg, in 21-day cycles
Area Under the Concentration Versus Time Curve (AUC)	181 ng*h/mL Geometric Coefficient of Variation 101	437 ng*h/mL Geometric Coefficient of Variation 16.7	711 ng*h/mL Geometric Coefficient of Variation NA CV% not calculable as 1 subject	1193 ng*h/mL Geometric Coefficient of Variation 48.3	1059 ng*h/mL Geometric Coefficient of Variation 15.3	5.95 ng*h/mL Geometric Coefficient of Variation 54.1	16.4 ng*h/mL Geometric Coefficient of Variation 51	30.4 ng*h/mL Geometric Coefficient of Variation 56.3

Adverse Events

Part 1a, Cohort 1

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Part 1a, Cohort 2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Part 1a, Cohort 3

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Part 1a, Cohort 4

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Part 1b, Cohort 1

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

Part 1b, Cohort 2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Part 1b, Cohort 3

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1a, Cohort 1 n=3 participants at risk USL311, intravenous, once per week, at 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 n=4 participants at risk USL311, intravenous, once per week, at 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3 n=3 participants at risk USL311, intravenous, once per week, at 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 n=3 participants at risk USL311, intravenous, once per week, at 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 n=6 participants at risk USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 n=3 participants at risk USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 n=4 participants at risk USL311, oral, once per day, 160 mg, in 21-day cycles
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Haemorrhage intracranial	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Seizure	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Encephalopathy	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Headache	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Psychiatric disorders Mental status changes	33.3% 1/3 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Renal and urinary disorders Acute kidney injury	33.3% 1/3 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Number of events 1 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.

Other adverse events

Other adverse events
Measure	Part 1a, Cohort 1 n=3 participants at risk USL311, intravenous, once per week, at 60 mg/m˄2, in 21-day cycles	Part 1a, Cohort 2 n=4 participants at risk USL311, intravenous, once per week, at 120 mg/m˄2, in 21-day cycles	Part 1a, Cohort 3 n=3 participants at risk USL311, intravenous, once per week, at 180 mg/m˄2, in 21-day cycles	Part 1a, Cohort 4 n=3 participants at risk USL311, intravenous, once per week, at 250 mg/m˄2, in 21-day cycles	Part 1b, Cohort 1 n=6 participants at risk USL311, oral, once per day, 40 mg, in 21-day cycles	Part 1b, Cohort 2 n=3 participants at risk USL311, oral, once per day, 80 mg, in 21-day cycles	Part 1b, Cohort 3 n=4 participants at risk USL311, oral, once per day, 160 mg, in 21-day cycles
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	50.0% 2/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	66.7% 2/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Investigations Blood creatinine increased	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Investigations Blood urea increased	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Investigations Gamma-glutamyltransferase increased	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Investigations Lymphocyte count decreased	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Psychiatric disorders Insomnia	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Psychiatric disorders Sleep disorders	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Gastrointestinal disorders Nausea	66.7% 2/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Gastrointestinal disorders Constipation	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Gastrointestinal disorders Gastrooesophageal reflux disease	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
General disorders Fatigue	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
General disorders Asthenia	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Gastrointestinal disorders Mucosal inflammation	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
General disorders Pyrexia	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Metabolism and nutrition disorders Hyponatraemia	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Headache	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Hypoaesthesia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Seizure	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Infections and infestations Bacteraemia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Infections and infestations Cystitis	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Skin and subcutaneous tissue disorders Erythema	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Vascular disorders Deep vein thrombosis	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	50.0% 2/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Ear and labyrinth disorders Ear discomfort	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Injury, poisoning and procedural complications Fall	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Reproductive system and breast disorders Cervical cyst	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Reproductive system and breast disorders Menopausal symptoms	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Amnesia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Aphasia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Brain oedema	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Cognitive disorder	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Facial paralysis	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Hemiparesis	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Hypersomnia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Nervous system disorders Memory Impairment	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
General disorders Gait disturbance	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Eye disorders Diplopia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	25.0% 1/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Eye disorders Vision blurred	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Investigations White blood cell count decreased	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Psychiatric disorders Confusional state	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 2/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	33.3% 1/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.
Vascular disorders Flushing	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	16.7% 1/6 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/3 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.	0.00% 0/4 • Adverse events collected from informed consent to last visit during treatment period (post treatment follow-up visit or end of treatment visit, whichever was last). Median duration of exposure was 5.14 (range 2.1-17.3) weeks for Part 1a (intravenous) subjects and 6.00 (range 0.3-30.0) for Part 1b (oral) subjects. Survival information only was collected during long term follow-up; for those who entered follow-up, follow-up was up to 25 months in Part 1a and up to 16 months in Part 1b. Study visits once per week during Treatment with adverse event collection, vital sign measurements, physical examination, neurologic examination and laboratory assessments at each visit. Safety electrocardiograms once per week first two 21-day cycles and then at beginning of each cycle and at the End of Treatment Visit. Survival information only was collected quarterly during long term follow-up. Deaths during follow-up phase were not captured as serious adverse events unless considered related.

Additional Information

Chief Medical Officer

Proximagen, LLC

Phone: 952-658-7440

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor has first right to first publication which is intended to be a joint, multi-center publication in conjunction with the Investigators. Following first publication, the Investigator may publish results provided the proposed publication is submitted for review to the Sponsor at least 60 days in advance; the Sponsor has the right to remove confidential/proprietary information. If publication may affect patentability of an invention, an additional delay of 90 days may be requested.
Publication restrictions are in place

Restriction type: OTHER