Trial Outcomes & Findings for An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 (Volasertib)in Combination With Oral BIBW 2992 (Afatinib) in Patients With Advanced Solid Tumours (NCT NCT01206816)

NCT ID: NCT01206816

Last Updated: 2019-02-01

Results Overview

MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, \<500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever \>38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 57 participants
• Primary outcome timeframe: 22 Days
• Results posted on: 2019-02-01

Participant Flow

Aspartate amino transferase (AST) ; Alanine amino transferase (ALT) and Eastern Cooperative Oncology Group (ECOG).

This is a Phase 1, open label, non randomised and dose escalation trial. There was no control group. The Combination of Volasertib and Afatinib to be investigated in two treatment schedules (A & B). In Schedule B the starting doses will be depend on the outcome of the MTD determination from treatment schedule A.

Participant milestones

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) Schedule A :Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) Schedule A :Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Overall Study STARTED	3	3	20	3	3	19	6
Overall Study COMPLETED	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	3	3	20	3	3	19	6

Reasons for withdrawal

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) Schedule A :Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) Schedule A :Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Overall Study Protocol Violation	0	0	1	0	0	0	0
Overall Study Withdrawal by Subject	0	0	1	0	0	0	0
Overall Study Progressive disease	3	3	13	3	3	16	3
Overall Study Other AE	0	0	4	0	0	3	2
Overall Study other than stated above	0	0	1	0	0	0	1

Baseline Characteristics

An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 (Volasertib)in Combination With Oral BIBW 2992 (Afatinib) in Patients With Advanced Solid Tumours

Baseline characteristics by cohort

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n=20 Participants Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n=3 Participants Schedule A : Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n=3 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n=19 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n=6 Participants Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Total n=57 Participants Total of all reporting groups
Age, Continuous	57.0 years STANDARD_DEVIATION 18.7 • n=5 Participants	48.7 years STANDARD_DEVIATION 6.1 • n=7 Participants	54.5 years STANDARD_DEVIATION 7.6 • n=5 Participants	57.0 years STANDARD_DEVIATION 10.8 • n=4 Participants	62.3 years STANDARD_DEVIATION 4.9 • n=21 Participants	61.9 years STANDARD_DEVIATION 9.3 • n=10 Participants	64.2 years STANDARD_DEVIATION 6.0 • n=115 Participants	58.3 years STANDARD_DEVIATION 9.4 • n=6 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	10 Participants n=10 Participants	3 Participants n=115 Participants	28 Participants n=6 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	9 Participants n=10 Participants	3 Participants n=115 Participants	29 Participants n=6 Participants
ECOG at screening 0	1 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=10 Participants	2 Participants n=115 Participants	20 Participants n=6 Participants
ECOG at screening 1	2 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	13 Participants n=10 Participants	3 Participants n=115 Participants	34 Participants n=6 Participants
ECOG at screening 2	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	3 Participants n=6 Participants
Tumour classification Head & neck cancers	0 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	9 Participants n=6 Participants
Tumour classification Non small cell lung	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Tumour classification Gastrointest. tract	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	2 Participants n=6 Participants
Tumour classification Colorectal (col/rec)	1 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	12 Participants n=10 Participants	2 Participants n=115 Participants	23 Participants n=6 Participants
Tumour classification Anal region	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Tumour classification Pancreas	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	5 Participants n=6 Participants
Tumour classification Biliary tree	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Tumour classification Genitourinary system	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Tumour classification Ureter	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Tumour classification Gynecologic cancers	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	2 Participants n=6 Participants
Tumour classification Cancers of breast	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	5 Participants n=6 Participants
Tumour classification Soft tissue/oss sarc	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants
Tumour classification Other	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	4 Participants n=6 Participants
Tumour classification Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=6 Participants

PRIMARY outcome

Timeframe: 22 Days

Population: Treated Set (TS)

MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, <500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever >38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2.

Outcome measures

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n=20 Participants Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n=3 Participants Schedule A :Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n=3 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n=19 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n=6 Participants Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Number of Participants With Dose Limiting Toxicities (DLT)	0 participants	0 participants	3 participants	2 participants	0 participants	5 participants	2 participants

PRIMARY outcome

Timeframe: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)

Population: Treated Set (TS)

Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The "3 + 3 design with de-escalation" for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days.

Outcome measures

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=29 Participants Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=28 Participants Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) Schedule A :Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib. Volasertib	300 mg	300 mg	—	—	—	—	—
Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib. Afatinib	30 mg	70 mg	—	—	—	—	—

SECONDARY outcome

Timeframe: After the first drug administration until 28 days after the last drug administration, up to 413 days.

Population: Treated Set (TS)

Number of patients with investigator defined drug-related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria v 3.0

Outcome measures

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n=20 Participants Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n=3 Participants Schedule A :Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n=3 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n=19 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n=6 Participants Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0	3 participants	3 participants	18 participants	3 participants	3 participants	19 participants	6 participants

SECONDARY outcome

Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

Population: Treated Set (TS)

Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR).

As Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

Outcome measures

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n=20 Participants Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n=3 Participants Schedule A :Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n=3 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n=19 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n=6 Participants Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Number of Patients With Objective Response (OR) Yes	1 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants
Number of Patients With Objective Response (OR) No	2 participants	3 participants	17 participants	3 participants	3 participants	15 participants	6 participants
Number of Patients With Objective Response (OR) Unknown	0 participants	0 participants	2 participants	0 participants	0 participants	4 participants	0 participants

SECONDARY outcome

Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

Population: Treated Set (TS)

Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response, partial response, stable disease, progressive disease or not evaluable.

As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

Outcome measures

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n=20 Participants Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n=3 Participants Schedule A :Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n=3 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n=19 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n=6 Participants Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Number of Patients With Best Overall Response. Stable disease	0 participants	0 participants	8 participants	0 participants	1 participants	5 participants	2 participants
Number of Patients With Best Overall Response. Progressive disease	2 participants	3 participants	8 participants	3 participants	2 participants	10 participants	4 participants
Number of Patients With Best Overall Response. Partial response	1 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants
Number of Patients With Best Overall Response. Complete response	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Patients With Best Overall Response. Not evaluable	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants
Number of Patients With Best Overall Response. Unknown	0 participants	0 participants	2 participants	0 participants	0 participants	4 participants	0 participants

SECONDARY outcome

Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

Population: Treated Set (TS)

Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Patients who had a best overall tumour response of complete response (CR), partial response (PR) or stable disease (SD) were assessed to show disease control.

As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

Outcome measures

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=3 Participants Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n=20 Participants Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n=3 Participants Schedule A :Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n=3 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n=19 Participants Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n=6 Participants Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Number of Patients With Disease Control YES	1 participants	0 participants	9 participants	0 participants	1 participants	5 participants	2 participants
Number of Patients With Disease Control NO	2 participants	3 participants	9 participants	3 participants	2 participants	10 participants	4 participants
Number of Patients With Disease Control Unknown	0 participants	0 participants	2 participants	0 participants	0 participants	4 participants	0 participants

Adverse Events

Volasertib150 mg+Afatinib 30 mg (Schedule A)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Volasertib 225 mg+Afatinib 30 mg (Schedule A)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Volasertib 300 mg+Afatinib 30 mg (Schedule A)

Serious events: 11 serious events

Other events: 18 other events

Deaths: 0 deaths

Volasertib 300 mg+Afatinib 40 mg (Schedule A)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Volasertib 300 mg+Afatinib 50 mg (Schedule B)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Volasertib 300 mg+Afatinib 70 mg (Schedule B)

Serious events: 12 serious events

Other events: 19 other events

Deaths: 0 deaths

Volasertib 300 mg+Afatinib 90 mg (Schedule B)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=3 participants at risk Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=3 participants at risk Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n=20 participants at risk Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n=3 participants at risk Schedule A : Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n=3 participants at risk Schedule B : Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n=19 participants at risk Schedule B : Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n=6 participants at risk Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.8% 3/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Ear and labyrinth disorders Ear haemorrhage	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Gastrointestinal obstruction	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Nausea	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Vomiting	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Chest pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Fatigue	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Mucosal haemorrhage	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Mucosal inflammation	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Oedema peripheral	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Hepatobiliary disorders Cholangitis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Device related infection	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Erysipelas	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Pneumonia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Puncture site infection	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Sepsis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Staphylococcal infection	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Cerebral haemorrhage	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Renal and urinary disorders Hydronephrosis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.

Other adverse events

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n=3 participants at risk Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n=3 participants at risk Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n=20 participants at risk Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n=3 participants at risk Schedule A : Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21. Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n=3 participants at risk Schedule B : Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n=19 participants at risk Schedule B : Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n=6 participants at risk Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21). Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Ageusia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Dizziness	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 2/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	35.0% 7/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	47.4% 9/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 4/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	40.0% 8/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	42.1% 8/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	50.0% 3/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	35.0% 7/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	47.4% 9/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 4/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Cardiac disorders Atrial fibrillation	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Cardiac disorders Sinus tachycardia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Cardiac disorders Tachycardia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Ear and labyrinth disorders Ear pain	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Ear and labyrinth disorders Vertigo	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Eye disorders Conjunctival haemorrhage	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Eye disorders Conjunctivitis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Eye disorders Dry eye	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Eye disorders Eye irritation	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Eye disorders Eyelids pruritus	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	35.0% 7/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	36.8% 7/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.8% 3/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Anal fissure	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Anal ulcer	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Ascites	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Constipation	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	20.0% 4/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	31.6% 6/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 2/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Diarrhoea	100.0% 3/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	75.0% 15/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	100.0% 3/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	94.7% 18/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	50.0% 3/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Dry mouth	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Dysphagia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Faeces pale	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Gastric ulcer	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Gastritis haemorrhagic	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Haemorrhoids	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Lip dry	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Nausea	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	50.0% 10/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	47.4% 9/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 2/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Odynophagia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Perianal erythema	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Salivary gland enlargement	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Stomatitis	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	40.0% 8/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	42.1% 8/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 4/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Gastrointestinal disorders Vomiting	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	35.0% 7/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	26.3% 5/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Asthenia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Catheter site haemorrhage	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Chest pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Fatigue	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	100.0% 3/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	55.0% 11/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	73.7% 14/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	50.0% 3/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Feeling cold	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Hernia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Inflammation	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Influenza like illness	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Mucosal inflammation	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	20.0% 4/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.8% 3/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Oedema	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Oedema peripheral	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Pain	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	20.0% 4/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Pyrexia	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	26.3% 5/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
General disorders Xerosis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Hepatobiliary disorders Haemorrhagic hepatic cyst	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Hepatobiliary disorders Hepatomegaly	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Immune system disorders Allergy to arthropod bite	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Cystitis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Herpes simplex	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Infection	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Lung infection	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Nasopharyngitis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.8% 3/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 2/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Neutropenic infection	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Oesophageal candidiasis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Osteomyelitis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Rash pustular	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Rhinitis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Tinea pedis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Infections and infestations Urinary tract infection	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Injury, poisoning and procedural complications Epicondylitis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Injury, poisoning and procedural complications Excoriation	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations Blood bilirubin increased	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations Blood creatinine increased	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations Ejection fraction decreased	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations Haemoglobin decreased	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations Hepatic enzyme increased	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations Neutrophil count decreased	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations Platelet count decreased	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations Weight decreased	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Investigations White blood cell count decreased	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Decreased appetite	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	55.0% 11/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	31.6% 6/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 2/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Hypoglycaemia	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	21.1% 4/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.8% 3/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Coccydynia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.8% 3/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Dysgeusia	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Headache	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	20.0% 4/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.8% 3/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Neuropathy peripheral	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Paraesthesia	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Nervous system disorders Transient ischaemic attack	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Psychiatric disorders Anxiety	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Psychiatric disorders Confusional state	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Psychiatric disorders Insomnia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	21.1% 4/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 2/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Renal and urinary disorders Bladder irritation	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Renal and urinary disorders Chromaturia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Renal and urinary disorders Dysuria	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Renal and urinary disorders Renal failure	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Renal and urinary disorders Renal vein thrombosis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Renal and urinary disorders Urethral pain	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Reproductive system and breast disorders Vaginal inflammation	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.0% 2/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Reproductive system and breast disorders Vulvovaginal dryness	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	20.0% 4/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Dysphonia	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	26.3% 5/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Epistaxis	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	30.0% 6/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	26.3% 5/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	50.0% 3/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Haemoptysis	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Nasal dryness	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Acne	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.0% 3/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	20.0% 4/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	21.1% 4/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 2/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Dermatitis	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	25.0% 5/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	15.8% 3/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Dry skin	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	20.0% 4/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	50.0% 3/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Erythema	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 2/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	10.5% 2/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Rash	100.0% 3/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	40.0% 8/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	66.7% 2/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	36.8% 7/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.0% 1/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Skin fissures	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	25.0% 5/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Skin and subcutaneous tissue disorders Skin toxicity	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Vascular disorders Hypertension	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Vascular disorders Hypotension	33.3% 1/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	16.7% 1/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.
Vascular disorders Vasoconstriction	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/20 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/3 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	5.3% 1/19 • After the first drug administration until 28 days after the last drug administration, upto 413 days.	0.00% 0/6 • After the first drug administration until 28 days after the last drug administration, upto 413 days.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• 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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Restriction type: OTHER