Trial Outcomes & Findings for Eribulin Mesylate Administered in Combination With Pemetrexed Versus Pemetrexed Alone as Second Line Therapy in Patients With Stage IIIB or IV Nonsquamous Non Small Cell Lung Cancer (NCT NCT01126736)

Last Updated: 2023-06-22

Results Overview

DLT were defined as clinically significant adverse events (AE) occurring less than or equal to (\<=) 21 days after treatment. Events as: Non-hematological: 1) Grade greater than or equal to (\>=) 3 peripheral neuropathy; 2) Grade \>=3 nausea, vomiting despite optimal antiemetic treatment; 3) Any nonhematologic toxicity of Grade \>=3, with exceptions as alopecia, single laboratory values out of normal range, hypersensitivity reaction. Hematological:1) Grade 4 neutropenia lasting \>7 days; 2) Febrile neutropenia as fever \>=38.5 degree Celsius with absolute neutrophil count less than (\<)1.0\*10\^9 per liter(/L); 3) Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4) Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1) Study drug related death; 2) Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

98 participants

Primary outcome timeframe

Cycle 1 (cycle length=21 days)

Results posted on

2023-06-22

Participant Flow

Participants took part in the study at 23 investigative sites in the United States, Germany, Italy, Ukraine, and the Czech Republic from 10 June 2010 to 18 March 2015.

A total of 15 participants were enrolled and treated in Phase 1b portion of the study and 83 participants were enrolled of which 80 participants received study treatment in Phase 2 portion of the study.

Participant milestones

Participant milestones
Measure	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed Participants received intravenous (IV) bolus of eribulin 0.9 milligram per square meter (mg/m\^2) in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 2, Arm 1: 0.9 mg/m^2 Eribulin Plus 500 mg/m^2 Pemetrexed Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.	Phase 2, Arm 2: 500 mg/m^2 Pemetrexed Participant received IV infused pemetrexed (500 mg/m\^2) alone on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.
Overall Study STARTED	4	6	5	42	41
Overall Study Safety Population	4	6	5	41	39
Overall Study Modified Intent-to-treat (MITT)	4	6	5	39	39
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	4	6	5	42	41

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed Participants received intravenous (IV) bolus of eribulin 0.9 milligram per square meter (mg/m\^2) in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 2, Arm 1: 0.9 mg/m^2 Eribulin Plus 500 mg/m^2 Pemetrexed Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.	Phase 2, Arm 2: 500 mg/m^2 Pemetrexed Participant received IV infused pemetrexed (500 mg/m\^2) alone on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.
Overall Study Death	2	2	1	19	19
Overall Study Completed 1 Year Follow-Up Per Protocol	0	0	0	3	3
Overall Study Lost to Follow-up	0	0	0	1	1
Overall Study Administrative reasons	0	0	0	0	1
Overall Study Progressive disease	0	0	0	2	1
Overall Study Withdrawal by Subject	0	0	0	1	1
Overall Study Other	2	4	4	16	15

Baseline Characteristics

Eribulin Mesylate Administered in Combination With Pemetrexed Versus Pemetrexed Alone as Second Line Therapy in Patients With Stage IIIB or IV Nonsquamous Non Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed n=4 Participants Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed n=6 Participants Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed n=5 Participants Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 2, Arm 1: 0.9 mg/m^2 Eribulin Plus 500 mg/m^2 Pemetrexed n=42 Participants Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.	Phase 2, Arm 2: 500 mg/m^2 Pemetrexed n=41 Participants Participant received IV infused pemetrexed (500 mg/m\^2) alone on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.	Total n=98 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	29 Participants n=4 Participants	27 Participants n=21 Participants	69 Participants n=10 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	13 Participants n=4 Participants	14 Participants n=21 Participants	29 Participants n=10 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	16 Participants n=4 Participants	14 Participants n=21 Participants	34 Participants n=10 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	26 Participants n=4 Participants	27 Participants n=21 Participants	64 Participants n=10 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=10 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	39 Participants n=4 Participants	40 Participants n=21 Participants	93 Participants n=10 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: Cycle 1 (cycle length=21 days)

Population: Phase 1b Safety Analysis Set was defined as all participants enrolled into the Phase 1b portion of this study.

Outcome measures

Outcome measures
Measure	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed n=6 Participants Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed n=5 Participants Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed n=4 Participants Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) Alanine transaminase (ALT) increased (grade 3)	1 Participants	1 Participants	0 Participants
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) Aspartate transaminase (AST) increased (grade 3)	1 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) Febrile neutropenia (grade 4)	1 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) Neutropenia (grade 4)	1 Participants	0 Participants	0 Participants
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) Pneumonia (grade 4)	0 Participants	1 Participants	0 Participants
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) Thrombocytopenia (grade 4)	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From date of first dose up to 30 days after the last dose of study drug in Phase 1b, up to approximately 1 year 2 months

Population: Phase 1b Safety Analysis Set was defined as all participants enrolled into the Phase 1b portion of this study.

Safety assessment included monitoring and recording all AE including all Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grades (for both increasing and decreasing severity), and serious adverse events (SAE); regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. A TEAE was defined as an AE that had on onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to the end of the study. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.

Outcome measures

Outcome measures
Measure	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed n=6 Participants Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed n=5 Participants Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed n=4 Participants Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.
Phase 1b: Percentage of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)	83.3 percentage of participants	100.0 percentage of participants	100.0 percentage of participants

PRIMARY outcome

Timeframe: From date of first dose up to 30 days after the last dose of study drug in Phase 2, up to approximately 3 years 6 months

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

Safety assessment included monitoring and recording all AE including all CTCAE version 4.0 grades (for both increasing and decreasing severity), and SAE; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and ECGs; and performance of physical examinations. A TEAE was defined as an AE that had on onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to the end of the study.

Outcome measures

Outcome measures
Measure	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed n=39 Participants Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed n=41 Participants Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.
Phase 2: Percentage of Participants Who Experienced TEAEs	94.9 percentage of participants	—	97.6 percentage of participants

SECONDARY outcome

Timeframe: From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 3 years 5 months)

Population: MITT population included all randomized participants who received at least one dose of study drug without major protocol eligibility violations.

PFS was defined as the time from the date of randomization until the earlier of the following two events: the date of progressive disease (PD) or the date of death. Progressive disease was defined as at least a 20 percent (%) increase in the sum of the longest diameter 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 based on investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). If a participant did not progress, they were censored at the date of last tumor assessment, last known alive date, or until the start of a next line of therapy, whichever occurred first. PFS was estimated using Kaplan-Meier method and presented with 2-sided 95% confidence interval.

Outcome measures

Outcome measures
Measure	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed n=39 Participants Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed n=39 Participants Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.
Phase 2: Progression-free Survival (PFS)	22.0 weeks Interval 12.14 to 29.0	—	18.1 weeks Interval 8.43 to 34.14

Adverse Events

Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed

Serious events: 4 serious events

Other events: 4 other events

Deaths: 2 deaths

Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed

Serious events: 3 serious events

Other events: 6 other events

Deaths: 2 deaths

Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed

Serious events: 4 serious events

Other events: 5 other events

Deaths: 1 deaths

Phase 2, Arm 1: 0.9 mg/m^2 Eribulin Plus 500 mg/m^2 Pemetrexed

Serious events: 13 serious events

Other events: 40 other events

Deaths: 19 deaths

Phase 2, Arm 2: 500 mg/m^2 Pemetrexed

Serious events: 7 serious events

Other events: 37 other events

Deaths: 19 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed n=4 participants at risk Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed n=6 participants at risk Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed n=5 participants at risk Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 2, Arm 1: 0.9 mg/m^2 Eribulin Plus 500 mg/m^2 Pemetrexed n=41 participants at risk Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.	Phase 2, Arm 2: 500 mg/m^2 Pemetrexed n=39 participants at risk Participant received IV infused pemetrexed (500 mg/m\^2) alone on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.
Blood and lymphatic system disorders Anaemia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	4.9% 2/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Leukopenia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Neutropenia	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Pancytopenia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Thrombocytopenia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Abdominal Pain	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Oesophageal Stenosis	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Asthenia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Fatigue	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Mucosal Inflammation	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Multi-Organ Failure	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Pyrexia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Hepatobiliary disorders Hepatitis	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Bronchopneumonia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Cellulitis	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Pneumonia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Sepsis Syndrome	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Injury, poisoning and procedural complications Spinal Compression Fracture	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Alanine Aminotransferase Increased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Aspartate Aminotransferase Increased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Hypochloraemia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Pleural Effusion	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases To Bone	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases To Central Nervous System	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Nervous system disorders Cerebral Infarction	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Nervous system disorders Cerebral Ischaemia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Nervous system disorders Loss Of Consciousness	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Nervous system disorders Myasthenic Syndrome	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Lung Disorder	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Pulmonary Haemorrhage	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Vascular disorders Embolism	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Cardiac disorders Cardiopulmonary failure	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)

Other adverse events

Other adverse events
Measure	Phase 1b, Arm 1 - Cohort 1: 0.9 mg/m^2 Eribulin Plus Pemetrexed n=4 participants at risk Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed 500 mg/m\^2 on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was escalated to 1.4 mg/m\^2 in Cohort 2 of Arm 1.	Phase 1b, Arm 1 - Cohort 2: 1.4 mg/m^2 Eribulin Plus Pemetrexed n=6 participants at risk Participants received IV bolus of eribulin 1.4 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 1b, Arm 2 - Cohort 1: 0.7 mg/m^2 Eribulin Plus Pemetrexed n=5 participants at risk Participants received IV bolus of eribulin 0.7 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle. On Day 1 only of each 21-day treatment cycle, participants also received IV infused pemetrexed (500 mg/m\^2). Participants within the same cohort received the same dose of eribulin. Participants also received dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed. The dose of eribulin was not further escalated.	Phase 2, Arm 1: 0.9 mg/m^2 Eribulin Plus 500 mg/m^2 Pemetrexed n=41 participants at risk Participants received IV bolus of eribulin 0.9 mg/m\^2 in combination with IV infused pemetrexed (500 mg/m\^2) on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.	Phase 2, Arm 2: 500 mg/m^2 Pemetrexed n=39 participants at risk Participant received IV infused pemetrexed (500 mg/m\^2) alone on Day 1 of each 21-day treatment cycle. Dexamethasone and vitamin supplements were administered as recommended in the prescribing information for pemetrexed.
Metabolism and nutrition disorders Hypocalcaemia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Hypokalaemia	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Hypomagnesaemia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Malnutrition	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Anaemia	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	33.3% 2/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	60.0% 3/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	14.6% 6/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	35.9% 14/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Leukopenia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	60.0% 3/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	17.9% 7/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Lymphopenia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Neutropenia	75.0% 3/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	50.0% 3/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	60.0% 3/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	31.7% 13/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	28.2% 11/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Thrombocytopenia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	4.9% 2/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	10.3% 4/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Blood and lymphatic system disorders Thrombocytosis	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Cardiac disorders Atrial Fibrillation	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Cardiac disorders Sinus Tachycardia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	10.3% 4/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Ear and labyrinth disorders Vertigo	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	4.9% 2/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Eye disorders Conjunctivitis Allergic	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Constipation	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	12.2% 5/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Diarrhoea	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	12.2% 5/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Dysphagia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Gastritis	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Nausea	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	40.0% 2/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	24.4% 10/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	15.4% 6/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Gastrointestinal disorders Vomiting	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.7% 3/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Asthenia	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	12.2% 5/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Chest Discomfort	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Chest Pain	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	4.9% 2/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	10.3% 4/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Chills	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Fatigue	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	40.0% 2/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	14.6% 6/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	30.8% 12/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Mucosal Inflammation	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Oedema	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Oedema Peripheral	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Pain	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
General disorders Pyrexia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	40.0% 2/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	12.2% 5/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Immune system disorders Seasonal Allergy	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Bacteraemia	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Bronchitis	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	9.8% 4/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Candidiasis	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Cellulitis	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Eye Infection	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Herpes Simplex	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Influenza	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	10.3% 4/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Oral Candidiasis	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Pneumonia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Infections and infestations Sepsis Syndrome	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Injury, poisoning and procedural complications Laceration	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Injury, poisoning and procedural complications Muscle Strain	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Injury, poisoning and procedural complications Poisoning	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Injury, poisoning and procedural complications Rib Fracture	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Alanine Aminotransferase Increased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	33.3% 2/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	26.8% 11/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	38.5% 15/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Aspartate Aminotransferase Increased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	24.4% 10/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	35.9% 14/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Blood Alkaline Phosphatase Increased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Blood Lactate Dehydrogenase Increased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Breath Sounds Abnormal	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	40.0% 2/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations C-Reactive Protein Increased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.6% 1/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Creatinine Renal Clearance Decreased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.7% 3/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Platelet Count Decreased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	33.3% 2/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations Weight Decreased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	10.3% 4/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Investigations White Blood Cell Count Decreased	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Decreased Appetite	75.0% 3/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	19.5% 8/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	12.8% 5/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Dehydration	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Diabetes Mellitus	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.7% 3/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Musculoskeletal and connective tissue disorders Back Pain	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.7% 3/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Nervous system disorders Headache	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	4.9% 2/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	10.3% 4/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Nervous system disorders Hypotonia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Psychiatric disorders Anxiety	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Psychiatric disorders Depression	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Psychiatric disorders Insomnia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Renal and urinary disorders Nocturia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Renal and urinary disorders Renal Failure	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	40.0% 2/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	9.8% 4/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	15.4% 6/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	40.0% 2/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Pleuritic Pain	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Rhonchi	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	40.0% 2/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Skin and subcutaneous tissue disorders Alopecia	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Skin and subcutaneous tissue disorders Dry Skin	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	2.4% 1/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Skin and subcutaneous tissue disorders Rash	50.0% 2/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	16.7% 1/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	40.0% 2/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.3% 3/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	7.7% 3/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Skin and subcutaneous tissue disorders Skin Ulcer	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Vascular disorders Aortic Aneurysm	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Vascular disorders Deep Vein Thrombosis	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	5.1% 2/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Vascular disorders Hot Flush	25.0% 1/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Vascular disorders Hypotension	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)
Vascular disorders Vasculitis	0.00% 0/4 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/6 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	20.0% 1/5 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/41 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 months)	0.00% 0/39 • Phase 1b: From date of first dose up to 30 days after the last dose of study drug in Phase 1b (up to approximately 1 years 2 months); Phase 2: From date of first dose up to 30 days after the last dose of study drug in Phase 2 (up to approximately 3 years 6 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