Trial Outcomes & Findings for Dose Finding Study of BI 6727 (Volasertib) in Patients With Various Solid Cancers (NCT NCT00969553)

Last Updated: 2019-07-26

Results Overview

Primary objective for this trial was to identify the MTD of volasertib for 2 dosing schedules. The MTD was defined as the highest volasertib dose studied for which the incidence of DLT was less than 2/6 patients. The MTD was defined on the basis of DLTs observed during the first treatment course only. In this outcome measure the percentage of participants with DLTs in cycle 1 is presented.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

59 participants

Primary outcome timeframe

From first administration of study drug up to 3 weeks

Results posted on

2019-07-26

Participant Flow

A Phase I single dose escalation study of two dosing schedules of Volasertib administered intravenously in Asian patients with various solid cancers with repeated administration in patients with clinical benefit

Investigator notified the sponsor if a patient qualified for study participation. Sponsor informed the investigator about the respective treatment schedule and the dose tier. After completing dose level 1 of D1 schedule (i.e. 100mg), dose level 2 of D1 schedule (i.e. 200mg) and dose level 1 of D1+D8 schedule (50mg on Days 1+8,every 3 weeks) started

Participant milestones

Participant milestones
Measure	V 100 mg D1 A single dose of 100 milligram (mg) volasertib (V) on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 minutes (min) using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 millilitre (mL) physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly intravenous (i.v.).	V 200 mg D1 A single dose of 200 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 250 mg D1 A single dose of 250 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 300 mg D1 A single dose of 300 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 350 mg D1 A single dose of 350 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 50 mg D1, D8 A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 100 mg D1, D8 A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 150 mg D1, D8 A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 200 mg D1, D8 A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.
Overall Study STARTED	3	3	6	17	3	4	4	16	3
Overall Study COMPLETED	0	0	0	1	0	0	0	2	0
Overall Study NOT COMPLETED	3	3	6	16	3	4	4	14	3

Reasons for withdrawal

Reasons for withdrawal
Measure	V 100 mg D1 A single dose of 100 milligram (mg) volasertib (V) on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 minutes (min) using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 millilitre (mL) physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly intravenous (i.v.).	V 200 mg D1 A single dose of 200 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 250 mg D1 A single dose of 250 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 300 mg D1 A single dose of 300 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 350 mg D1 A single dose of 350 mg volasertib on Day 1 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 50 mg D1, D8 A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 100 mg D1, D8 A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 150 mg D1, D8 A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.	V 200 mg D1, D8 A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course. Volasertib was administered as a short infusion over 120 min using an infusion pump. Immediately following the infusion of volasertib, the infusion tubing was washed with 100 mL physiological sodium chloride (0.9% NaCl) solution for a maximum duration of 10 min volasertib was administered strictly i.v.
Overall Study Progressive disease (PD)	2	2	6	9	2	4	2	12	3
Overall Study Dose limiting Toxicity (DLT)	0	0	0	0	1	0	0	0	0
Overall Study Other Adverse Event	0	0	0	1	0	0	1	0	0
Overall Study Refused cont. medication	1	1	0	2	0	0	0	1	0
Overall Study Not specified above	0	0	0	4	0	0	1	1	0

Baseline Characteristics

Dose Finding Study of BI 6727 (Volasertib) in Patients With Various Solid Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.	Total n=59 Participants Total of all reporting groups
Age, Continuous	69.7 years STANDARD_DEVIATION 8.0 • n=5 Participants	55.7 years STANDARD_DEVIATION 9.3 • n=7 Participants	52.0 years STANDARD_DEVIATION 4.7 • n=5 Participants	53.4 years STANDARD_DEVIATION 11.4 • n=4 Participants	52.3 years STANDARD_DEVIATION 9.1 • n=21 Participants	48.5 years STANDARD_DEVIATION 8.5 • n=8 Participants	51.5 years STANDARD_DEVIATION 18.2 • n=8 Participants	60.2 years STANDARD_DEVIATION 10.0 • n=24 Participants	66.7 years STANDARD_DEVIATION 3.1 • n=42 Participants	56.2 years STANDARD_DEVIATION 11.1 • n=42 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	2 Participants n=8 Participants	7 Participants n=24 Participants	1 Participants n=42 Participants	24 Participants n=42 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	12 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	2 Participants n=8 Participants	9 Participants n=24 Participants	2 Participants n=42 Participants	35 Participants n=42 Participants

PRIMARY outcome

Timeframe: From first administration of study drug up to 3 weeks

Population: The treated set consisted of all patients whe received at least one dose of volasertib.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Percentage of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib	0.0 percentage of participants	0.0 percentage of participants	16.7 percentage of participants	23.5 percentage of participants	100 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	66.7 percentage of participants

PRIMARY outcome

Timeframe: From the first administration of study drug up to 3 weeks

Population: The treated set.

Outcome measures

Outcome measures
Measure	V100 D1 n=17 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=16 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
MTD of Volasertib	300 milligram (mg)	150 milligram (mg)	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first administration of volasertib to 21 days after the last dose, up to 548 days

Population: Treated Set

Percentage of participants with incidence and intensity of drug-related AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v.3.0. This endpoint will be presented as a percentage of patients with adverse event by treatment and the highest CTCAE grade of the related AE.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Percentage of Participants With Incidence and Intensity of Drug-related AEs According to CTCAE v.3.0 CTCAE Grade 1	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	5.9 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Incidence and Intensity of Drug-related AEs According to CTCAE v.3.0 CTCAE Grade 2	0.0 Percentage of participants	66.7 Percentage of participants	33.3 Percentage of participants	11.8 Percentage of participants	0.0 Percentage of participants	25.0 Percentage of participants	50.0 Percentage of participants	43.8 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Incidence and Intensity of Drug-related AEs According to CTCAE v.3.0 CTCAE Grade 3	33.3 Percentage of participants	0.0 Percentage of participants	16.7 Percentage of participants	35.3 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	18.8 Percentage of participants	33.3 Percentage of participants
Percentage of Participants With Incidence and Intensity of Drug-related AEs According to CTCAE v.3.0 CTCAE Grade 4	0.0 Percentage of participants	0.0 Percentage of participants	33.3 Percentage of participants	29.4 Percentage of participants	100.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	6.3 Percentage of participants	66.7 Percentage of participants
Percentage of Participants With Incidence and Intensity of Drug-related AEs According to CTCAE v.3.0 CTCAE Grade 5	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Visit 1, prior to first administration of volasertib) and up to 21 days after last observation on treatment (up to 548 days)

Population: Treated Set

This endpoint will be presented as a change from baseline to last value on treatment in platelets.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Change From Baseline to Last Value on Treatment in Platelets	-30 10^9 platelets/ Litre (L) Standard Deviation 48	-62 10^9 platelets/ Litre (L) Standard Deviation 30	-5 10^9 platelets/ Litre (L) Standard Deviation 114	-10 10^9 platelets/ Litre (L) Standard Deviation 173	-55 10^9 platelets/ Litre (L) Standard Deviation 150	-18 10^9 platelets/ Litre (L) Standard Deviation 29	-69 10^9 platelets/ Litre (L) Standard Deviation 29	-94 10^9 platelets/ Litre (L) Standard Deviation 111	42 10^9 platelets/ Litre (L) Standard Deviation 119

SECONDARY outcome

Timeframe: Baseline (Visit 1, prior to first administration of volasertib) and up to 21 days after last observation on treatment (up to 548 days)

Population: Treated Set

This endpoint will be presented as a change from baseline to last value on treatment in neutrophils.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Change From Baseline to Last Value on Treatment in Neutrophils	0.9 10^9 neutrophils / Litre (L) Standard Deviation 3.4	-1.4 10^9 neutrophils / Litre (L) Standard Deviation 1.1	-1.3 10^9 neutrophils / Litre (L) Standard Deviation 1.9	-0.8 10^9 neutrophils / Litre (L) Standard Deviation 3.2	-0.7 10^9 neutrophils / Litre (L) Standard Deviation 3.2	1.3 10^9 neutrophils / Litre (L) Standard Deviation 1.4	1.0 10^9 neutrophils / Litre (L) Standard Deviation 4.4	-1.4 10^9 neutrophils / Litre (L) Standard Deviation 2.6	3.1 10^9 neutrophils / Litre (L) Standard Deviation 6.4

SECONDARY outcome

Timeframe: From first administration of volasertib to the last dose, up to 527 days

Population: Treated Set

This endpoint will present the best clinical assessment. The investigator will perform a clinical assessment. An evaluation will be done whether the patient appears to be clinically improved, unchanged, or deteriorated. The presented numbers show the percentage of patients.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Patient Performance Unknown	0 percentage of participants 48	0 percentage of participants 30	0 percentage of participants 114	6 percentage of participants 173	0 percentage of participants 150	0 percentage of participants 29	0 percentage of participants 29	0 percentage of participants 111	0 percentage of participants 119
Patient Performance Improved	0 percentage of participants	0 percentage of participants	0 percentage of participants	6 percentage of participants	67 percentage of participants	25 percentage of participants	0 percentage of participants	13 percentage of participants	0 percentage of participants
Patient Performance Unchanged	100 percentage of participants	100 percentage of participants	100 percentage of participants	88 percentage of participants	33 percentage of participants	50 percentage of participants	75 percentage of participants	81 percentage of participants	100 percentage of participants
Patient Performance Deteriorated	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	25 percentage of participants	25 percentage of participants	6 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Visit 1, prior to the first administration of volasertib), up to 21 days after last observation on treatment (up to 548 days)

Population: Treated Set

This endpoint will be presented as a change from baseline at last observation of systolic blood pressure (SBP), diastolic blood pressure (DBP) in millimeter of mercury (mmHg) and pulse rate (PR) in beats per minute (bpm). In this outcome measure SBP and DBP are presented.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Vital Signs (Blood Pressure) SBP, chg from baseline at last observation	-19.0 mmHg Standard Deviation 19.5	4.7 mmHg Standard Deviation 14.2	0.0 mmHg Standard Deviation 8.3	-1.0 mmHg Standard Deviation 19.1	-12.3 mmHg Standard Deviation 10.8	6.0 mmHg Standard Deviation 12.7	1.5 mmHg Standard Deviation 11.0	-8.9 mmHg Standard Deviation 16.9	-3.3 mmHg Standard Deviation 7.6
Vital Signs (Blood Pressure) DBP, chg from baseline at last observation	-4.0 mmHg Standard Deviation 9.0	2.0 mmHg Standard Deviation 5.0	-1.3 mmHg Standard Deviation 11.3	-1.9 mmHg Standard Deviation 11.3	-7.7 mmHg Standard Deviation 10.0	10.3 mmHg Standard Deviation 9.0	2.3 mmHg Standard Deviation 10.4	-2.9 mmHg Standard Deviation 8.2	1.0 mmHg Standard Deviation 6.2

SECONDARY outcome

Timeframe: Baseline (Visit 1, prior to the first administration of volasertib), up to 21 days after last observation on treatment (up to 548 days)

Population: Treated Set

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Vital Signs (Pulse Rate)	18.3 bpm Standard Deviation 10.3	9.7 bpm Standard Deviation 15.5	16.5 bpm Standard Deviation 5.8	10.4 bpm Standard Deviation 16.5	2.7 bpm Standard Deviation 12.1	13.5 bpm Standard Deviation 7.0	10.0 bpm Standard Deviation 5.0	5.1 bpm Standard Deviation 18.9	12.7 bpm Standard Deviation 8.5

SECONDARY outcome

Timeframe: Baseline, 2 hours (before the end of infusion of volasertib) and 24 hours after first infusion in Cycle 1

Population: Treated Set, only the patients in the Maximum Tolerated Dose (MTD) groups are evaluated for this endpoint.

This endpoint will be presented as a change from individual baseline in QT interval, corrected according to Fridericias formula (QTcF) to end of infusion (2 hours) and 24 hours after first infusion in Cycle 1.

Outcome measures

Outcome measures
Measure	V100 D1 n=17 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=16 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
ECG Change from baseline after 2 hours	21.0 milliseconds (ms) Standard Deviation 10.6	13.9 milliseconds (ms) Standard Deviation 7.7	—	—	—	—	—	—	—
ECG Change from baseline after 24 hours	5.2 milliseconds (ms) Standard Deviation 10.4	6.3 milliseconds (ms) Standard Deviation 9.7	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure)

Population: The treated set

The objective response (OR) was defined as complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest) assessed by tumour measurement and evaluated according to the Response Evaluation Criteria in solid tumours (RECIST), version 1.0. The data represents the percentage of patients.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Objective Response OR: no or unknown	100 percentage of patients	100 percentage of patients	100 percentage of patients	100 percentage of patients	67 percentage of patients	100 percentage of patients	100 percentage of patients	94 percentage of patients	100 percentage of patients
Objective Response OR: yes	0 percentage of patients	0 percentage of patients	0 percentage of patients	0 percentage of patients	33 percentage of patients	0 percentage of patients	0 percentage of patients	6 percentage of patients	0 percentage of patients

SECONDARY outcome

Timeframe: At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure)

Population: The treated set

Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. PFS was assessed by tumour measurement and evaluated according to RECIST, version 1.0.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Progression-free Survival	83.0 days Interval 48.0 to 211.0	62.0 days Interval 37.0 to 84.0	48.0 days Interval 43.0 to 82.0	49.0 days Interval 30.0 to 139.0	274.0 days Interval 49.0 to 274.0	42.5 days Interval 8.0 to 254.0	92.0 days Interval 8.0 to 267.0	58.0 days Interval 8.0 to 499.0	45.0 days Interval 43.0 to 56.0

SECONDARY outcome

Timeframe: From first drug administration up to at 3 month interval after final End of treatment visit until disease progression, death, or lost to follow-up, up to 548 days

Population: The reason not to analyze the duration of objective response is that only 2 patients in different arms achieved an objective response and the analysis would reduce to a single patient case report.

The duration of overall response was measured from the time measurement criteria were met for complete response (CR) or partial response (PR), whichever was recorded first, until the first date that recurrent or progressive disease was objectively documented. The duration of overall CR was measured from the time measurement criteria were first met for CR until the first date that recurrent disease was objectively documented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure)

Population: The treated set

The disease control (DC) presented are the percentage of patients with CR, PR or stable disease as best response throughout the study assessed by tumour measurement and evaluated according to RECIST, version 1.0.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Disease Control DC: yes	67 percentage of patients	67 percentage of patients	33 percentage of patients	41 percentage of patients	67 percentage of patients	25 percentage of patients	50 percentage of patients	63 percentage of patients	0 percentage of patients
Disease Control DC: no or unknown	33 percentage of patients	33 percentage of patients	67 percentage of patients	59 percentage of patients	33 percentage of patients	75 percentage of patients	50 percentage of patients	38 percentage of patients	100 percentage of patients

SECONDARY outcome

Timeframe: At screening and at the end of every other treatment course up to 527 days (= longest treatment exposure)

Population: No descriptive statistics were calculated, but the time profile of sum of largest diameter was plotted for each patient.

The individual time profile of the sum of the largest diameters of target lesions (LD) is presented graphically for each patient in the Clinical Trial Report (CTR) only. No descriptive statistics were planned.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Both schedules: 10 minutes prior to first drug administration and 1 hour (h), 2, 2:30, 3, 4, 8, 24, 336h thereafter; additional planned times in schedule D1+D8: 167:50, 169, 170, 170:30, 171, 172, 176, 192h; additional planned time in D1 schedule: 168h

Population: Treated Set. All evaluable patients were included in the PK analyses. Patients who were considered not evaluable were not included. A patient was considered to be not evaluable if they had an important protocol violation relevant to the evaluation of PK, or they had insufficient data.

The PK of volasertib will be presented for the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) for the population attending the D1 schedule, the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 168 hours (AUC0-168) for the population attending the D1+ D8 schedule and the maximum measured concentration of volasertib in plasma (Cmax). In this outcome measure AUC0-∞ is presented.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=5 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=16 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=2 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Pharmacokinetics (PK) AUC0-∞ of Volasertib	2140 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 15.9	3280 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 28.6	6140 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 38.9	6260 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 40.3	9790 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 14.6	—	—	—	—

SECONDARY outcome

Population: Treated Set. All evaluable patients were included in the PK analyses.

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=2 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=14 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=2 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Pharmacokinetics (PK) AUC0-168 of Volasertib AUC0-168, 1st infusion	590 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 20.8	1380 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 1.01	1890 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 54.4	3320 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 0.317	—	—	—	—	—
Pharmacokinetics (PK) AUC0-168 of Volasertib AUC0-168, 2nd infusion	847 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 16.7	1870 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 19.8	2620 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 67.1	4300 in nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 16.0	—	—	—	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	V100 D1 n=3 Participants A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 Participants A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=5 Participants A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=16 Participants A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 Participants A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 Participants A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=3 Participants A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=15 Participants A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 Participants A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Pharmacokinetics (PK) Cmax of Volasertib After infusion Day 1	186 ng/mL Geometric Coefficient of Variation 7.87	540 ng/mL Geometric Coefficient of Variation 31.5	540 ng/mL Geometric Coefficient of Variation 37.0	489 ng/mL Geometric Coefficient of Variation 33.1	675 ng/mL Geometric Coefficient of Variation 3.19	106 ng/mL Geometric Coefficient of Variation 67.3	234 ng/mL Geometric Coefficient of Variation 2.99	235 ng/mL Geometric Coefficient of Variation 32.5	410 ng/mL Geometric Coefficient of Variation 22.1
Pharmacokinetics (PK) Cmax of Volasertib After infusion Day 8	—	—	—	—	—	104 ng/mL Geometric Coefficient of Variation 47.6	212 ng/mL Geometric Coefficient of Variation 31.9	240 ng/mL Geometric Coefficient of Variation 49.4	431 ng/mL Geometric Coefficient of Variation 1.15

Adverse Events

V100 D1

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

V200 D1

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

V250 D1

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

V300 D1

Serious events: 7 serious events

Other events: 17 other events

Deaths: 0 deaths

V350 D1

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

V50 D1, D8

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

V100 D1, D8

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

V150 D1, D8

Serious events: 7 serious events

Other events: 16 other events

Deaths: 0 deaths

V200 D1, D8

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	V100 D1 n=3 participants at risk A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 participants at risk A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 participants at risk A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 participants at risk A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 participants at risk A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 participants at risk A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 participants at risk A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 participants at risk A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 participants at risk A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Ileus	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Vomiting	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Device occlusion	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Fatigue	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Pyrexia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	12.5% 2/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Hepatobiliary disorders Bile duct obstruction	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Abdominal wall abscess	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Infection	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Liver abscess	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Injury, poisoning and procedural complications Femur fracture	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations C-reactive protein increased	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	12.5% 2/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Nervous system disorders Hepatic encephalopathy	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Renal and urinary disorders Haematuria	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)

Other adverse events

Other adverse events
Measure	V100 D1 n=3 participants at risk A single dose of 100 mg volasertib on Day 1 every 3-week course.	V200 D1 n=3 participants at risk A single dose of 200 mg volasertib on Day 1 every 3-week course.	V250 D1 n=6 participants at risk A single dose of 250 mg volasertib on Day 1 every 3-week course.	V300 D1 n=17 participants at risk A single dose of 300 mg volasertib on Day 1 every 3-week course.	V350 D1 n=3 participants at risk A single dose of 350 mg volasertib on Day 1 every 3-week course.	V50 D1, D8 n=4 participants at risk A single dose of 50 mg volasertib on Day 1 and Day 8 every 3-week course.	V100 D1, D8 n=4 participants at risk A single dose of 100 mg volasertib on Day 1 and Day 8 every 3-week course.	V150 D1, D8 n=16 participants at risk A single dose of 150 mg volasertib on Day 1 and Day 8 every 3-week course.	V200 D1, D8 n=3 participants at risk A single dose of 200 mg volasertib on Day 1 and Day 8 every 3-week course.
Gastrointestinal disorders Abdominal distension	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	17.6% 3/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 4/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 2/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Ear and labyrinth disorders Tinnitus	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	83.3% 5/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	41.2% 7/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	100.0% 3/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	37.5% 6/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	100.0% 3/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Blood and lymphatic system disorders Leukopenia	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	50.0% 3/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	76.5% 13/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	50.0% 2/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	37.5% 6/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Blood and lymphatic system disorders Neutropenia	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 2/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	70.6% 12/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	100.0% 3/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	37.5% 6/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Blood and lymphatic system disorders Thrombocytopenia	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	50.0% 3/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	70.6% 12/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	100.0% 3/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Cardiac disorders Palpitations	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Abdominal tenderness	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Ascites	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Cheilitis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Constipation	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	31.2% 5/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	12.5% 2/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Duodenal ulcer	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Dysphagia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Flatulence	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Gastroduodenal ulcer	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Gingival pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Mouth ulceration	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	18.8% 3/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Nausea	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	23.5% 4/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 4/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Oral pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Periodontal disease	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Reflux oesophagitis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Stomatitis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Toothache	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Gastrointestinal disorders Vomiting	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	50.0% 2/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	18.8% 3/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Asthenia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Chest discomfort	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Chest pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Chills	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Device occlusion	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Fatigue	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	50.0% 3/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	29.4% 5/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Malaise	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Mucosal inflammation	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	12.5% 2/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Oedema	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Oedema peripheral	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	12.5% 2/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Pyrexia	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	23.5% 4/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	12.5% 2/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
General disorders Tenderness	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Hepatobiliary disorders Bile duct obstruction	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Immune system disorders Hypersensitivity	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Bacteraemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Cellulitis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Escherichia infection	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Infection	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Nasopharyngitis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Pneumonia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Infections and infestations Urinary tract infection	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Injury, poisoning and procedural complications Excoriation	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	12.5% 2/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Injury, poisoning and procedural complications Penis injury	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Injury, poisoning and procedural complications Procedural complication	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Injury, poisoning and procedural complications Wound	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Alanine aminotransferase increased	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Aspartate aminotransferase increased	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Blood bilirubin increased	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Blood creatinine increased	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Blood lactate dehydrogenase increased	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Electrocardiogram QRS complex abnormal	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Investigations Weight decreased	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	18.8% 3/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Cachexia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Decreased appetite	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 2/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	23.5% 4/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	18.8% 3/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	50.0% 2/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 2/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	12.5% 2/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Nervous system disorders Convulsion	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Nervous system disorders Dizziness	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 2/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	18.8% 3/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Nervous system disorders Headache	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Nervous system disorders Hemiparesis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Nervous system disorders Hypoaesthesia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Nervous system disorders Neuropathy peripheral	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Psychiatric disorders Confusional state	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Psychiatric disorders Delirium	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Psychiatric disorders Depression	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Psychiatric disorders Insomnia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	50.0% 2/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Renal and urinary disorders Dysuria	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Renal and urinary disorders Haematuria	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Renal and urinary disorders Nocturia	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Renal and urinary disorders Pollakiuria	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Renal and urinary disorders Proteinuria	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Renal and urinary disorders Renal failure acute	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Renal and urinary disorders Urinary retention	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Reproductive system and breast disorders Scrotal pain	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Reproductive system and breast disorders Vaginal discharge	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Cough	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	17.6% 3/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	18.8% 3/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	75.0% 3/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	18.8% 3/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Haemoptysis	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Pleuritic pain	66.7% 2/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Respiratory, thoracic and mediastinal disorders Sputum increased	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	16.7% 1/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Eczema	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	33.3% 1/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Hair colour changes	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	11.8% 2/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	18.8% 3/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Skin and subcutaneous tissue disorders Skin disorder	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	50.0% 2/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	6.2% 1/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Vascular disorders Flushing	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	5.9% 1/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)
Vascular disorders Hypertension	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/6 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/17 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	25.0% 1/4 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/16 • From inclusion into the study to 21 days after last drug administration (up to 548 days)	0.00% 0/3 • From inclusion into the study to 21 days after last drug administration (up to 548 days)

Additional Information

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Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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