Trial Outcomes & Findings for Testing the Addition of KRT-232 (AMG 232) to Usual Chemotherapy for Relapsed Multiple Myeloma (NCT NCT03031730)
NCT ID: NCT03031730
Last Updated: 2026-02-10
Results Overview
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
35 participants
Primary outcome timeframe
at least 6 months of treatment, an average of 1 year
Results posted on
2026-02-10
Participant Flow
Study opened to accrual on 10/2017 at 6 sites across ETCTN network (MD Anderson, UC Davis, UT San Antonio, UT Austin, University of Utah, Weill Cornell). Study closed to accrual 07/2024 due to uncertain development plan of MDM2 inhibitors in myeloma and slow accrual after discussion with NCI CTEP leadership and study industry collaborator, Kartos Therapeutics.
Accrual process was slow due to various reasons including multiple screen failures for reasons including inability to perform integral biomarker testing for TP53 mutation status due to \<5% plasma cells in bone marrow biopsy at screening, TP53 mutation detected, not having measurable disease, and low creatinine clearance below eligibility threshold. 35 patients were consented, of those16 patients were eligible and dosed.
Participant milestones
| Measure |
Part A (Dose-escalation) 60mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 90mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 120mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 190mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 240mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part B (Dose-expansion)
10 patient dose-exansion at RP2D determined from Part A
|
|---|---|---|---|---|---|---|
|
60 mg
STARTED
|
6
|
0
|
0
|
0
|
0
|
0
|
|
60 mg
COMPLETED
|
3
|
0
|
0
|
0
|
0
|
0
|
|
60 mg
NOT COMPLETED
|
3
|
0
|
0
|
0
|
0
|
0
|
|
90mg
STARTED
|
0
|
10
|
0
|
0
|
0
|
0
|
|
90mg
COMPLETED
|
0
|
3
|
0
|
0
|
0
|
0
|
|
90mg
NOT COMPLETED
|
0
|
7
|
0
|
0
|
0
|
0
|
|
120mg
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
120mg
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
120mg
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
190mg
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
190mg
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
190mg
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
240mg
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
240mg
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
240mg
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Part A (Dose-escalation) 60mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 90mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 120mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 190mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 240mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part B (Dose-expansion)
10 patient dose-exansion at RP2D determined from Part A
|
|---|---|---|---|---|---|---|
|
60 mg
Adverse Event
|
2
|
0
|
0
|
0
|
0
|
0
|
|
60 mg
Alternative Treatment
|
1
|
0
|
0
|
0
|
0
|
0
|
|
90mg
Death
|
0
|
1
|
0
|
0
|
0
|
0
|
|
90mg
Physician Decision
|
0
|
1
|
0
|
0
|
0
|
0
|
|
90mg
Withdrawal by Subject
|
0
|
2
|
0
|
0
|
0
|
0
|
|
90mg
Alternative Treatment
|
0
|
1
|
0
|
0
|
0
|
0
|
|
90mg
TP53 mutation or indeterminate TP53 mutation status
|
0
|
2
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Testing the Addition of KRT-232 (AMG 232) to Usual Chemotherapy for Relapsed Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Part A (Dose-escalation) 60 mg
n=6 Participants
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 90 mg
n=10 Participants
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 120 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 190 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 240 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
—
|
—
|
—
|
0 Participants
n=140 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=41 Participants
|
6 Participants
n=1581 Participants
|
—
|
—
|
—
|
9 Participants
n=140 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=41 Participants
|
4 Participants
n=1581 Participants
|
—
|
—
|
—
|
7 Participants
n=140 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=41 Participants
|
4 Participants
n=1581 Participants
|
—
|
—
|
—
|
7 Participants
n=140 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=41 Participants
|
6 Participants
n=1581 Participants
|
—
|
—
|
—
|
9 Participants
n=140 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=41 Participants
|
2 Participants
n=1581 Participants
|
—
|
—
|
—
|
5 Participants
n=140 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=41 Participants
|
8 Participants
n=1581 Participants
|
—
|
—
|
—
|
11 Participants
n=140 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
—
|
—
|
—
|
0 Participants
n=140 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
—
|
—
|
—
|
0 Participants
n=140 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=41 Participants
|
1 Participants
n=1581 Participants
|
—
|
—
|
—
|
1 Participants
n=140 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
—
|
—
|
—
|
0 Participants
n=140 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=41 Participants
|
2 Participants
n=1581 Participants
|
—
|
—
|
—
|
2 Participants
n=140 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=41 Participants
|
6 Participants
n=1581 Participants
|
—
|
—
|
—
|
10 Participants
n=140 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
—
|
—
|
—
|
0 Participants
n=140 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=41 Participants
|
1 Participants
n=1581 Participants
|
—
|
—
|
—
|
3 Participants
n=140 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=41 Participants
|
10 participants
n=1581 Participants
|
—
|
—
|
—
|
16 participants
n=140 Participants
|
PRIMARY outcome
Timeframe: at least 6 months of treatment, an average of 1 yearPopulation: Only included DLT-evaluable patients. 6 of 6 patients enrolled on Dose Level 1 and 5 of 10 patients at dose level 2 were DLT-evaluable. Therefore, the primary outcome of determining the safety and tolerability beyond dose level one was not possible, and the MTD and recommended phase 2 dose could not be evaluated prior to study closure.
Outcome measures
| Measure |
Part A: Dose Level 1
n=6 Participants
KRT-232 60 mg + KRd
|
Part A: Dose Level 2
n=5 Participants
KRT-232 90 mg + KRd
|
|---|---|---|
|
Evaluate Safety and Tolerability of KRT-232 (AMG 232) in Combination With Carfilzomib, Lenalidomdie, and Dexamethasone (KRd)
|
1 Dose Limiting Toxicity
|
1 Dose Limiting Toxicity
|
PRIMARY outcome
Timeframe: at least 6 months of treatment, an average of 1 yearPopulation: Only included DLT-evaluable patients. 6 of 6 patients enrolled on Dose Level 1 and 5 of 10 patients at dose level 2 were DLT-evaluable. Therefore, the primary outcome of determining the safety and tolerability beyond dose level one was not possible, and the MTD and recommended phase 2 dose could not be evaluated prior to study closure.
Outcome measures
| Measure |
Part A: Dose Level 1
n=6 Participants
KRT-232 60 mg + KRd
|
Part A: Dose Level 2
n=5 Participants
KRT-232 90 mg + KRd
|
|---|---|---|
|
Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of KRT-232 (AMG 232) in Combination With Carfilzomib, Lenalidomdie, and Dexamethasone (KRd)
|
NA mg
6 of 6 patients enrolled on Dose Level 1 and 5 of 10 patients at dose level 2 were DLT-evaluable. Therefore, the primary outcome of determining the safety and tolerability beyond dose level one was not possible, and the MTD and recommended phase 2 dose could not be evaluated prior to study closure.
|
NA mg
6 of 6 patients enrolled on Dose Level 1 and 5 of 10 patients at dose level 2 were DLT-evaluable. Therefore, the primary outcome of determining the safety and tolerability beyond dose level one was not possible, and the MTD and recommended phase 2 dose could not be evaluated prior to study closure.
|
SECONDARY outcome
Timeframe: 30 days after last dosePopulation: Data were not collected due to study termination prior to participants' assessment at the pre-specified time points.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 30 days after last dosePopulation: Data were not collected due to study termination prior to participants' assessment at the pre-specified time points.
Outcome measures
Outcome data not reported
Adverse Events
Part A (Dose-escalation) 60 mg
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Part A (Dose-escalation) 90 mg
Serious events: 7 serious events
Other events: 10 other events
Deaths: 1 deaths
Part A (Dose-escalation) 120 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Part A (Dose-escalation) 190 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Part A (Dose-escalation) 240 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part A (Dose-escalation) 60 mg
n=6 participants at risk
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 90 mg
n=10 participants at risk
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 120 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 190 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 240 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
|---|---|---|---|---|---|
|
Eye disorders
Eye disorders - Other, specify - Vision Decreased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Eye disorders
Eye pain
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Infections & infestations - Other - Covid-19 Infection
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Pancreatitis
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Nervous system disorders
Stroke
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Lung infection
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Urinary tract infection
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
Other adverse events
| Measure |
Part A (Dose-escalation) 60 mg
n=6 participants at risk
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 90 mg
n=10 participants at risk
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 120 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 190 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
Part A (Dose-escalation) 240 mg
Escalating doses of KRT-232 (DL1 60 mg, DL2 90 mg, DL3 120 mg, DL4 190 mg, DL5 240 mg) in combination with Carfilzomib, Lenalidomide, Dexamethasone (KRd)
|
|---|---|---|---|---|---|
|
General disorders
Pain
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Fatigue
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
60.0%
6/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
White blood cell decreased
|
100.0%
6/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
60.0%
6/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Lymphocyte count decreased
|
83.3%
5/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
60.0%
6/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Platelet count decreased
|
100.0%
6/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
40.0%
4/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Blood and lymphatic system disorders
Anemia
|
83.3%
5/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
40.0%
4/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
3/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
60.0%
6/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
83.3%
5/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
40.0%
4/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Neutrophil count decreased
|
100.0%
6/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Nausea
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
60.0%
6/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
66.7%
4/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
66.7%
4/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
66.7%
4/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Psychiatric disorders
Insomnia
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
40.0%
4/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
50.0%
3/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Alkaline phosphatase increased
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Creatinine increased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Edema limbs
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
50.0%
3/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
ALT increased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Anorexia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Chills
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Nervous system disorders
Dizziness
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
30.0%
3/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Fever
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Investigations - Other, specify - Blood Bicarbonate Decreased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Investigations - Other, specify - Ldh Increased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
AST increased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Blood bilirubin increased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Skin and subcutaneous tissue disorders
Bruising
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Cataract
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Renal and urinary disorders
Cystitis noninfective
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Nervous system disorders
Dysgeusia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Renal and urinary disorders
Hematuria
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Vascular disorders
Hypertension
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Investigations - Other, specify - Blood Lactate Dehydrogenase Increased
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Investigations - Other, specify - Hyperphosphatemia
|
33.3%
2/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Mucositis oral
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Renal and urinary disorders
Proteinuria
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
20.0%
2/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Vascular disorders
Superficial thrombophlebitis
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Urinary tract infection
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Cardiac disorders
AV block first degree
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Anxiety
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Cardiac troponin T increased
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Cardiac disorders
Chest pain - cardiac
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Dry eye
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Dysphagia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
EKG QT corrected interval prolong
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Ejection fraction decreased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Endocarditis infective
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Eye disorders - Other, specify - Blurred Vision Bilateral
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Eye disorders - Other, specify - Left Eye Stye
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Floaters
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Flushing
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
GGT increased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Gait disturbance
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Vascular disorders
Hypotension
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Infections & infestations - Other - Shingles
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Infections & infestations - Other - Viral Infections Nos
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Infusion related reaction
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Investigations - Other, specify - Bbc Decreased
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Investigations - Other, specify - Total Protein Decreased
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Investigations
Investigations - Other, specify - Total Protein Increased
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Irritability
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Libido decreased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Nervous system disorders
Memory impairment
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition - Other - Blood Bicarbonate Decreased
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition - Other - Hyperphosphatemia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Musculoskeletal and connective tissue disorders
Musculoskel/connect tissue -Other - Muscle Cramp
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Musculoskeletal and connective tissue disorders
Musculoskel/connect tissue -Other - Muscle Cramps - Hands
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Oral hemorrhage
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Cardiac disorders
Palpitations
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Toothache
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal mucositis
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Skin and subcutaneous tissue disorders
Purpura
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
General disorders
Reproductive and breast - Other - Vaginal Itching
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Gastrointestinal disorders
Salivary duct inflammation
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Cardiac disorders
Sinus bradycardia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Skin and subcutaneous tissue disorders
Skin & subcutaneous tissue -Other - Facial Tightening
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Skin infection
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Nervous system disorders
Tremor
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Upper respiratory infection
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Renal and urinary disorders
Urinary tract pain
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
10.0%
1/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
|
Cardiac disorders
Ventricular arrhythmia
|
16.7%
1/6 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
0.00%
0/10 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
—
0/0 • At least 6 months of treatment, an average of 1 year
No patients were enrolled under Part A (Dose-escalation) 120, 190 and 240 mg.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60