Trial Outcomes & Findings for Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer (NCT NCT01347645)

Last Updated: 2023-06-22

Results Overview

MTD: maximum dose that was determined to be safe and tolerable for Phase 2.If two dose limiting toxicities (DLTs) occurred at any dose level,MTD: preceding dose/intermediate dose.DLT was graded according to CTCAE v4.0. Includes \>= Grade 3(G3) peripheral neuropathy,\>=G3 nausea/vomiting despite optimal anti-emetic treatment, any other non-hematologic toxicity of \>=G3(except alopecia, single abnormal laboratory values Investigator judged unlikely related to study therapy, had no clinical correlate, resolved in 7 days, hypersensitivity reaction to any of compounds),Grade 4 neutropenia lasting over 7 days,febrile neutropenia(defined as fever \>=38.5 degrees Celsius with absolute neutrophil count below 1.0\*10\^9 per liter, G3 thrombocytopenia with nontraumatic bleeding(without therapeutic systemic anticoagulation)requiring platelet transfusion,Grade 4 thrombocytopenia (with/without nontraumatic bleeding),any study drug-related death,other toxicity dose escalation committee believed to be DLT.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

82 participants

Primary outcome timeframe

Up to 12 cycles (each cycle length =14 days)

Results posted on

2023-06-22

Participant Flow

Participants took part in the study at 42 investigative sites in Argentina, Australia, Brazil, Russian Federation, Ukraine, and the United States from 30 September 2011 to 22 June 2015.

A total of 82 participants were enrolled in this study. This study consisted of two phases: Phase 1b and Phase 2. In Phase 1b, 14 participants were enrolled and received study treatment and in Phase 2, 68 participants were enrolled and received the study treatment. Participants were randomized in a 1:1 ratio and received either E7820 in combination with irinotecan or FOLFIRI.

Participant milestones

Participant milestones
Measure	Phase 1b: Cohort 1: E7820 40 mg + Irinotecan Participants received E7820 40 milligram (mg) tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 milligram per square meter (mg/m\^2) as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until disease progression (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 2: E7820 70 mg + Irinotecan Participants received E7820 70 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 3: E7820 100 mg + Irinotecan Participants received E7820 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: E7820 70 mg + Irinotecan Participants received E7820 70 mg (changed to 50 mg as per protocol amendment 06) as Recommended Phase 2 dose (RP2D) tablets, orally, once daily of each 14-day treatment cycle on Day 1 with Irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Overall Study STARTED	3	8	3	34	34
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	3	8	3	34	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b: Cohort 1: E7820 40 mg + Irinotecan Participants received E7820 40 milligram (mg) tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 milligram per square meter (mg/m\^2) as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until disease progression (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 2: E7820 70 mg + Irinotecan Participants received E7820 70 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 3: E7820 100 mg + Irinotecan Participants received E7820 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: E7820 70 mg + Irinotecan Participants received E7820 70 mg (changed to 50 mg as per protocol amendment 06) as Recommended Phase 2 dose (RP2D) tablets, orally, once daily of each 14-day treatment cycle on Day 1 with Irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Overall Study Death	1	5	2	7	7
Overall Study Lost to Follow-up	1	1	0	1	1
Overall Study Study termination by Sponsor due to E7820 plus irinotecan being potentially inferior to FOLFIRI	0	2	1	22	20
Overall Study Other	1	0	0	0	1
Overall Study Withdrawal by Subject	0	0	0	3	3
Overall Study Physician Decision	0	0	0	0	1
Overall Study Adverse Event	0	0	0	1	1

Baseline Characteristics

Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b: Cohort 1: E7820 40 mg + Irinotecan n=3 Participants Participants received E7820 40 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 milligram per square meter (mg/m\^2) as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 2: E7820 70 mg + Irinotecan n=8 Participants Participants received E7820 70 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 3: E7820 100 mg + Irinotecan n=3 Participants Participants received E7820 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: E7820 70 mg + Irinotecan n=34 Participants Participants received E7820 70 mg (changed to 50 mg as per protocol amendment 06) as Recommended Phase 2 dose (RP2D) tablets, orally, once daily of each 14-day treatment cycle on Day 1 with Irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri n=34 Participants Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Total n=82 Participants Total of all reporting groups
Age, Customized <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants
Age, Customized Between 18 and 85 years	3 Participants n=99 Participants	8 Participants n=107 Participants	3 Participants n=206 Participants	34 Participants n=7 Participants	34 Participants n=31 Participants	82 Participants n=30 Participants
Age, Customized >=85 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	3 Participants n=107 Participants	1 Participants n=206 Participants	19 Participants n=7 Participants	16 Participants n=31 Participants	40 Participants n=30 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	5 Participants n=107 Participants	2 Participants n=206 Participants	15 Participants n=7 Participants	18 Participants n=31 Participants	42 Participants n=30 Participants

PRIMARY outcome

Timeframe: Up to 12 cycles (each cycle length =14 days)

Population: The safety population included all the participants enrolled in the Phase 1b portion of this study, except for those who (i) dropped out of the study prior to receiving any study drug, or (ii) were without any safety assessment following the first dose of study drug.

Outcome measures

Outcome measures
Measure	Phase 1b, All Participants n=14 Participants Participants received E7820 40 mg, 70 mg and 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Phase 1b: Maximum Tolerated Dose (MTD) of E7820 With Irinotecan as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0	NA milligram (mg) The MTD for E7820 in combination with irinotecan was not determined. Based on dose reductions and interruptions at the 100 mg dose, it was decided that the E7820 Phase 2 dose would be 70 mg once daily.	—

PRIMARY outcome

Timeframe: From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)

Population: The safety population included all participants enrolled and randomized to treatment in the Phase 2 portion of this study, except for those who (i) dropped out prior to receiving any study drug, or (ii) were without any safety assessment following the first dose of study drug.

TEAE is defined as an adverse event that had an onset date, or a worsening in severity on or after the first dose of study drug up to the end of the study. Number of participants with TEAEs are reported based on safety assessments of laboratory tests, physical examination, examining bowel movements, regular measurement of vital signs, eastern cooperative oncology group-performance status and electrocardiogram parameter values. SAE is any untoward medical occurrence that at any dose: resulted in death; life threatening required inpatient hospitalization; resulted in persistent, significant disability; is congenital anomaly/birth defect or medically important due to other reasons than above mentioned criteria. Number of participants with TEAEs and SAEs were reported.

Outcome measures

Outcome measures
Measure	Phase 1b, All Participants n=34 Participants Participants received E7820 40 mg, 70 mg and 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri n=34 Participants Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	34 Participants	34 Participants
Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	10 Participants	8 Participants

SECONDARY outcome

Timeframe: From date of randomization up to 1 year and 2 months

Population: Modified intent-to-treat (MITT) analysis set included all participants who were randomized and received at least one dose of study medication without major protocol eligibility violations.

PFS is defined as the time from the date of randomization of a participant until the sooner of (1) the date of first documented progression of such participant's disease (PD) based on Investigator assessments according to response evaluation criteria in solid tumor (RECIST) version (v) 1.1. or; (2) the date of such participant's death due to any cause. PD is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Phase 1b, All Participants n=34 Participants Participants received E7820 40 mg, 70 mg and 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri n=34 Participants Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Phase 2: Progression Free Survival (PFS)	17.1 weeks Interval 9.0 to 32.29	33.7 weeks Interval 24.14 to 45.43

SECONDARY outcome

Timeframe: From date of randomization up to 1 year and 2 months

Population: MITT analysis set included all participants who were randomized and received at least one dose of study medication without major protocol eligibility violations.

OS is defined as time from the date of randomization of a participant until the date of death of such participant, regardless of the actual cause of the participant's death.

Outcome measures

Outcome measures
Measure	Phase 1b, All Participants n=34 Participants Participants received E7820 40 mg, 70 mg and 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri n=34 Participants Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Phase 2: Overall Survival (OS)	NA weeks Overall survival could not be estimated due to insufficient number of participants reached the event during the study.	NA weeks Overall survival could not be estimated due to insufficient number of participants reached the event during the study.

SECONDARY outcome

Timeframe: From date of randomization up to 1 year and 2 months

Population: MITT analysis set included all participants who were randomized and received at least one dose of study medication without major protocol eligibility violations.

TTP is defined as time from the date of randomization of a participant until the date of first documented progression of such participant's disease. PD is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking in reference the smallest summed longest diameters on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression.

Outcome measures

Outcome measures
Measure	Phase 1b, All Participants n=34 Participants Participants received E7820 40 mg, 70 mg and 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri n=34 Participants Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Phase 2: Time to Progression (TTP)	23.7 weeks Interval 14.43 to 33.0	33.7 weeks Interval 24.14 to 45.43

SECONDARY outcome

Timeframe: From date of randomization up to 1 year and 2 months

Population: MITT analysis set included all participants who were randomized and received at least one dose of study medication without major protocol eligibility violations.

ORR is defined as percentage of participants in the study whose best overall response is either complete response (CR) or partial response (PR) based on RECIST v1.1. CR is defined as complete disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to less than 10 mm. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline summed longest diameters.

Outcome measures

Outcome measures
Measure	Phase 1b, All Participants n=34 Participants Participants received E7820 40 mg, 70 mg and 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri n=34 Participants Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Phase 2: Percentage of Participants With Overall Response	20.6 percentage of participants Interval 8.7 to 37.9	20.6 percentage of participants Interval 8.7 to 37.9

Adverse Events

Phase 1b: Cohort 1: E7820 40 mg + Irinotecan

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Phase 1b: Cohort 2: E7820 70 mg + Irinotecan

Serious events: 1 serious events

Other events: 8 other events

Deaths: 5 deaths

Phase 1b: Cohort 3: E7820 100 mg + Irinotecan

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase 2: E7820 70 mg + Irinotecan

Serious events: 10 serious events

Other events: 33 other events

Deaths: 7 deaths

Phase 2: Folfiri

Serious events: 8 serious events

Other events: 33 other events

Deaths: 7 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1b: Cohort 1: E7820 40 mg + Irinotecan n=3 participants at risk Participants received E7820 40 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 milligram per square meter (mg/m\^2) as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 2: E7820 70 mg + Irinotecan n=8 participants at risk Participants received E7820 70 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 3: E7820 100 mg + Irinotecan n=3 participants at risk Participants received E7820 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: E7820 70 mg + Irinotecan n=34 participants at risk Participants received E7820 70 mg (changed to 50 mg as per protocol amendment 06) as Recommended Phase 2 dose (RP2D) tablets, orally, once daily of each 14-day treatment cycle on Day 1 with Irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri n=34 participants at risk Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Colitis	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Gastroenteritis	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Cardiac disorders Cardiovascular insufficiency	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Intestinal obstruction	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Pyrexia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Thrombosis in device	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Clostridium difficile colitis	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Device related infection	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Lobar pneumonia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Lung infection	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Alanine aminotransferase increased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Nervous system disorders Loss of consciousness	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Renal and urinary disorders Haematuria	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)

Other adverse events

Other adverse events
Measure	Phase 1b: Cohort 1: E7820 40 mg + Irinotecan n=3 participants at risk Participants received E7820 40 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 milligram per square meter (mg/m\^2) as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 2: E7820 70 mg + Irinotecan n=8 participants at risk Participants received E7820 70 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 1b: Cohort 3: E7820 100 mg + Irinotecan n=3 participants at risk Participants received E7820 100 mg tablets, orally, once daily of each 14-day treatment cycle in combination with irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle (once every 2 weeks) for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: E7820 70 mg + Irinotecan n=34 participants at risk Participants received E7820 70 mg (changed to 50 mg as per protocol amendment 06) as Recommended Phase 2 dose (RP2D) tablets, orally, once daily of each 14-day treatment cycle on Day 1 with Irinotecan 180 mg/m\^2 as an intravenous infusion on Day 1 of each 14-day cycle for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.	Phase 2: Folfiri n=34 participants at risk Participants received the FOLFIRI regimen, which consisted of irinotecan at 180 mg/m\^2 as an intravenous infusion and leucovorin at 200 mg/m\^2 by intravenous infusion on Day 1 of each cycle, and 5-FU at 400 mg/m\^2 as an intravenous bolus injection followed by a total of 2400 mg/m\^2 by continuous IV infusion over 46 hours over Days 1 and 2 via infusion for up to 12 cycles. After 12 cycles, at the discretion of the Investigator and in consultation with the Medical Monitor, participants who were experiencing clinical benefit continued their assigned treatment until PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
Renal and urinary disorders Haematuria	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Renal and urinary disorders Urinary retention	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Reproductive system and breast disorders Pelvic discomfort	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	37.5% 3/8 • Number of events 6 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	66.7% 2/3 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	32.4% 11/34 • Number of events 25 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	23.5% 8/34 • Number of events 19 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	37.5% 3/8 • Number of events 8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	29.4% 10/34 • Number of events 49 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	23.5% 8/34 • Number of events 19 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	50.0% 4/8 • Number of events 18 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 5 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	55.9% 19/34 • Number of events 81 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	55.9% 19/34 • Number of events 52 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 10 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Ear and labyrinth disorders Ear pain	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Eye disorders Blepharospasm	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Eye disorders Cataract	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Eye disorders Eye swelling	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Eye disorders Macular degeneration	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Eye disorders Periorbital oedema	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Eye disorders Vision blurred	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Abdominal discomfort	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	66.7% 2/3 • Number of events 9 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	14.7% 5/34 • Number of events 6 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	17.6% 6/34 • Number of events 13 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Abdominal pain lower	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	37.5% 3/8 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	11.8% 4/34 • Number of events 10 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Diarrhoea	100.0% 3/3 • Number of events 20 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	75.0% 6/8 • Number of events 9 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	100.0% 3/3 • Number of events 9 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	47.1% 16/34 • Number of events 45 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	41.2% 14/34 • Number of events 49 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Dry mouth	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Dysphagia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Epigastric discomfort	33.3% 1/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Flatulence	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Gastrointestinal tract irritation	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Mouth ulceration	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Nausea	100.0% 3/3 • Number of events 23 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	50.0% 4/8 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	66.7% 2/3 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	26.5% 9/34 • Number of events 18 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	47.1% 16/34 • Number of events 58 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Stomatitis	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	11.8% 4/34 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	66.7% 2/3 • Number of events 9 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	26.5% 9/34 • Number of events 22 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Asthenia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	17.6% 6/34 • Number of events 9 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	26.5% 9/34 • Number of events 19 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Chills	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Fatigue	66.7% 2/3 • Number of events 18 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	62.5% 5/8 • Number of events 6 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	66.7% 2/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	20.6% 7/34 • Number of events 11 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	26.5% 9/34 • Number of events 12 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Generalised oedema	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Influenza like illness	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Mucosal inflammation	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 5 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Pyrexia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	17.6% 6/34 • Number of events 9 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Immune system disorders Drug hypersensitivity	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Immune system disorders Hypersensitivity	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Upper respiratory tract infection	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Urinary tract infection	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Injury, poisoning and procedural complications Meniscus injury	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Alanine aminotransferase increased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	11.8% 4/34 • Number of events 6 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Aspartate aminotransferase increased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Blood calcium decreased	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Hepatic enzyme increased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Lymphocyte count decreased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Neutrophil count decreased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	66.7% 2/3 • Number of events 6 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Weight decreased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Weight increased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations White blood cell count decreased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	66.7% 2/3 • Number of events 7 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Acidosis	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Decreased appetite	100.0% 3/3 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	11.8% 4/34 • Number of events 5 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 5 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 7 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 7 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Hypomagnesaemia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 5 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Nervous system disorders Headache	66.7% 2/3 • Number of events 6 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Nervous system disorders Neuropathy peripheral	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Nervous system disorders Transient ischaemic attack	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Psychiatric disorders Anxiety	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Psychiatric disorders Confusional state	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Psychiatric disorders Depression	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Psychiatric disorders Insomnia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	33.3% 1/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Nasal inflammation	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Rales	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Skin and subcutaneous tissue disorders Alopecia	66.7% 2/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	47.1% 16/34 • Number of events 20 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	14.7% 5/34 • Number of events 6 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	66.7% 2/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Skin and subcutaneous tissue disorders Night sweats	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	12.5% 1/8 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	25.0% 2/8 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Vascular disorders Hypertension	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Vascular disorders Hypotension	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Blood and lymphatic system disorders Lymphopenia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	11.8% 4/34 • Number of events 7 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 6 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
General disorders Oedema peripheral	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Respiratory tract infection	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	11.8% 4/34 • Number of events 4 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Respiratory tract infection viral	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Infections and infestations Viral infection	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Blood bilirubin increased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Blood creatinine increased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Investigations Creatinine renal clearance decreased	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	8.8% 3/34 • Number of events 8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	11.8% 4/34 • Number of events 13 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	2.9% 1/34 • Number of events 1 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Nervous system disorders Dysgeusia	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/34 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)
Vascular disorders Venous thrombosis limb	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/8 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	0.00% 0/3 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)	5.9% 2/34 • Number of events 2 • From the first dose of study drug up to 28 days after last dose (Up to 1 year and 3 months)

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: +1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place