Trial Outcomes & Findings for A Phase I/II Open Label Extension Study of BIBF 1120 Administered Orally Once or Twice Daily to Establish Safety, Pharmacokinetics and Efficacy in Patients With Advanced Solid Tumours and Clinical Benefit From Previous Therapy With BIBF 1120 (NCT NCT00715403)

NCT ID: NCT00715403

Last Updated: 2014-12-02

Results Overview

All patients who had grade 1 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 41 participants
• Primary outcome timeframe: From signing the informed consent until final follow-up, up to 991 days
• Results posted on: 2014-12-02

Participant Flow

This was a multinational, open-label, uncontrolled, extension trial with Nintedanib in patients who had experienced a clinical benefit with Nintedanib (objective tumour response or disease stabilisation and/or symptom improvement) in either one out of five phase I or phase I/IIA clinical trials for advanced solid tumours at study entry.

Participant milestones

Measure	50mg QD Patients were treated with 50 mg Nintedanib once daily (QD) in the morning.	200mg QD Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID Patients were treated with 100 mg Nintedanib twice daily (BID).	150mg BID Patients were treated with 150 mg Nintedanib twice daily.	200mg BID Patients were treated with 200 mg Nintedanib twice daily.	250mg BID Patients were treated with 250 mg Nintedanib twice daily.	300mg BID Patients were treated with 300 mg Nintedanib twice daily.
Overall Study STARTED	1	1	4	9	6	19	1
Overall Study COMPLETED	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	1	1	4	9	6	19	1

Reasons for withdrawal

Measure	50mg QD Patients were treated with 50 mg Nintedanib once daily (QD) in the morning.	200mg QD Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID Patients were treated with 100 mg Nintedanib twice daily (BID).	150mg BID Patients were treated with 150 mg Nintedanib twice daily.	200mg BID Patients were treated with 200 mg Nintedanib twice daily.	250mg BID Patients were treated with 250 mg Nintedanib twice daily.	300mg BID Patients were treated with 300 mg Nintedanib twice daily.
Overall Study Progressive disease	0	1	3	9	5	14	1
Overall Study Dose limiting Toxicity (DLT)	0	0	0	0	0	1	0
Overall Study Other Adverse Event than DLT	1	0	0	0	0	2	0
Overall Study Protocol Violation	0	0	0	0	0	1	0
Overall Study Other reason not defined above	0	0	1	0	1	1	0

Baseline Characteristics

A Phase I/II Open Label Extension Study of BIBF 1120 Administered Orally Once or Twice Daily to Establish Safety, Pharmacokinetics and Efficacy in Patients With Advanced Solid Tumours and Clinical Benefit From Previous Therapy With BIBF 1120

Baseline characteristics by cohort

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.	Total n=41 Participants Total of all reporting groups
Age, Continuous	75.0 years n=5 Participants	47.0 years n=7 Participants	65.5 years n=5 Participants	66.0 years n=4 Participants	63.5 years n=21 Participants	66.0 years n=10 Participants	67.0 years n=115 Participants	66.0 years n=24 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	8 Participants n=24 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants	4 Participants n=21 Participants	18 Participants n=10 Participants	1 Participants n=115 Participants	33 Participants n=24 Participants

PRIMARY outcome

Timeframe: From signing the informed consent until final follow-up, up to 991 days

Population: Treated set

All patients who had grade 1 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Incontinence	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Cough	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Abdominal distension	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Anorexia	100 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	16 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Hyperhidrosis	100 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Dyspepsia	100 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Fatigue	100 percentage of participants	0 percentage of participants	0 percentage of participants	33 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Nasopharyngitis	100 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	33 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Diarrhoea	0 percentage of participants	100 percentage of participants	0 percentage of participants	44 percentage of participants	50 percentage of participants	37 percentage of participants	100 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Bronchitis	0 percentage of participants	100 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Eye disorder	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Musculoskeletal pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Eyelid oedema	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Haemorrhoids	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Toothache	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Pyrexia	0 percentage of participants	0 percentage of participants	25 percentage of participants	11 percentage of participants	17 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Muscle spasms	0 percentage of participants	0 percentage of participants	25 percentage of participants	11 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Pain in extremity	0 percentage of participants	0 percentage of participants	25 percentage of participants	11 percentage of participants	17 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Vulvovaginal dryness	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Abdominal pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	33 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Xerosis	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Gastrointestinal infection	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Musculoskeletal chest pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Dizziness	0 percentage of participants	0 percentage of participants	0 percentage of participants	22 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Headache	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Anxiety	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Rales	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Rash	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Vertigo	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Constipation	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	16 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Flatulence	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Hypersensitivity	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Viral infection	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Sciatica	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Dyspnoea	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	33 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Sinus tachycardia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Eye pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Visual impairment	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Chest pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Chills	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Hepatic pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Weight decreased	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Hyperglycaemia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Muscular weakness	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Back pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Dysgeusia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Peripheral sensory neuropathy	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Haematuria	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Alopecia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Dry skin	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Pruritus	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Conjunctivitis	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	100 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Haemoptysis	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	100 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Gastrointestinal haemorrhage	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Adverse drug reaction	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Rash maculo-papular	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Neck pain	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Urinary tract infection	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Joint swelling	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Insomnia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Arrhythmia	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Nausea	0 percentage of participants	0 percentage of participants	0 percentage of participants	33 percentage of participants	67 percentage of participants	21 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Vomiting	0 percentage of participants	0 percentage of participants	0 percentage of participants	22 percentage of participants	33 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Gastrooesophageal reflux disease	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Tooth discolouration	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Asthenia	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	33 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Bone pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	22 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Arthralgia	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	50 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Myalgia	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	100 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Nail disorder	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Hot flush	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Gastric disorder	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Balance disorder	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Carpal tunnel syndrome	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 1 Dysuria	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: From signing the informed consent until final follow-up, up to 991 days

Population: Treated set

All patients who had grade 2 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Fatigue	0 percentage of participants	0 percentage of participants	0 percentage of participants	22 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Anorexia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Diarrhoea	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	33 percentage of participants	21 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Bronchitis	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Nausea	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Vomiting	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Abdominal pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Asthenia	0 percentage of participants	0 percentage of participants	25 percentage of participants	11 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Bone pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Arthralgia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Musculoskeletal pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Sciatica	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Dyspnoea	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Weight decreased	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Cough	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Haemoptysis	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Osteoarthritis	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Parotitis	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Osteolysis	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Abdominal pain upper	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Gastrointestinal disorder	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Groin pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Neutropenia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Gamma-glutamyltransferase increased	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Dehydration	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Productive cough	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Gastrointestinal infection	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Musculoskeletal chest pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Headache	0 percentage of participants	0 percentage of participants	25 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Constipation	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Flatulence	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Chest pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Urinary tract infection	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Back pain	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Peripheral sensory neuropathy	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	17 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Anaemia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Oedema peripheral	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Deep vein thrombosis	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 2 Phlebitis superficial	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: From signing the informed consent until final follow-up, up to 991 days

Population: Treated set

All patients who had grade 3 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Dyspnoea	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Lymphopenia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Ileus	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Urinary tract obstruction	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Gamma-glutamyltransferase increased	100 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Diarrhoea	0 percentage of participants	0 percentage of participants	25 percentage of participants	11 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Diarrhoea infectious	0 percentage of participants	0 percentage of participants	25 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Constipation	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Haemorrhoids	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Subileus	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Vomiting	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Pneumonia	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Convulsion	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Renal failure	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 3 Pleural effusion	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: From signing the informed consent until final follow-up, up to 991 days

Population: Treated set

All patients who had grade 4 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 4	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: From signing the informed consent until final follow-up, up to 991 days

Population: Treated set

All patients who had grade 5 adverse events (AEs) as the worst grade of the AE. Incidence and intensity of Adverse Events with grading of Adverse Events according to Common Terminology Criteria for Adverse Events (CTCAE).

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 5 Subdural Haematoma	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Incidence and Intensity of Adverse Events With Highest CTCAE Grade 5 Malignant neoplasm progression	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	26 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: From signing the informed consent until end of treatment, up to 991 days

Population: Treated set.

Difference from baseline (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=18 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Difference From Baseline for Liver Enzymes Alkaline phosphatase	127.0 U/L Standard Error 0.0	11.9 U/L Standard Error 0.0	-39.0 U/L Standard Error 70.5	-21.2 U/L Standard Error 96.4	-11.7 U/L Standard Error 81.0	16.0 U/L Standard Error 180.9	7.2 U/L Standard Error 0.0
Difference From Baseline for Liver Enzymes Alanine aminotransferase	10.6 U/L Standard Error 0.0	6.6 U/L Standard Error 0.0	0.6 U/L Standard Error 11.1	-1.6 U/L Standard Error 18.8	9.1 U/L Standard Error 45.4	17.0 U/L Standard Error 33.6	12.4 U/L Standard Error 0.0
Difference From Baseline for Liver Enzymes Aspartate aminotransferase	14.3 U/L Standard Error 0.0	13.7 U/L Standard Error 0.0	9.6 U/L Standard Error 18.0	6.8 U/L Standard Error 9.1	4.3 U/L Standard Error 41.0	15.9 U/L Standard Error 35.1	7.6 U/L Standard Error 0.0

PRIMARY outcome

Timeframe: From signing the informed consent until end of treatment, up to 991 days

Population: Treated set.

Difference from baseline (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=18 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Difference From Baseline for Bilirubin, Creatinine and Glucose Creatinine	-0.1 mg/dL Standard Error 0.0	-0.3 mg/dL Standard Error 0.0	0.0 mg/dL Standard Error 0.2	-0.1 mg/dL Standard Error 0.0	-0.1 mg/dL Standard Error 0.2	-0.1 mg/dL Standard Error 0.3	0.0 mg/dL Standard Error 0.0
Difference From Baseline for Bilirubin, Creatinine and Glucose Bilirubin (total)	0.5 mg/dL Standard Error 0.0	0.0 mg/dL Standard Error 0.0	0.0 mg/dL Standard Error 0.2	0.0 mg/dL Standard Error 0.3	0.1 mg/dL Standard Error 0.1	0.1 mg/dL Standard Error 0.3	0.0 mg/dL Standard Error 0.0
Difference From Baseline for Bilirubin, Creatinine and Glucose Glucose (N=1,1,3,9,4,14,1)	-60.0 mg/dL Standard Error 0.0	-2.2 mg/dL Standard Error 0.0	28.9 mg/dL Standard Error 126.1	-11.3 mg/dL Standard Error 75.1	-76.5 mg/dL Standard Error 75.9	-23.3 mg/dL Standard Error 52.2	-40.0 mg/dL Standard Error 0.0

PRIMARY outcome

Timeframe: From baseline until end of treatment, up to 991 days

Population: Treated set.

Difference from baseline for Haemoglobin (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=18 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Difference From Baseline for Haemoglobin	-1.8 g/dL Standard Error 0.0	1.4 g/dL Standard Error 0.0	0.4 g/dL Standard Error 2.3	1.0 g/dL Standard Error 1.3	1.2 g/dL Standard Error 0.7	-0.2 g/dL Standard Error 2.1	1.1 g/dL Standard Error 0.0

PRIMARY outcome

Timeframe: From signing the informed consent until end of treatment, up to 991 days

Population: Treated set.

Difference from baseline (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=18 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Difference From Baseline for Haematology and Differentials Parameters Platelets	42.2 10^9 /L Standard Error 0.0	11.1 10^9 /L Standard Error 0.0	1.0 10^9 /L Standard Error 83.7	-2.5 10^9 /L Standard Error 25.2	-38.1 10^9 /L Standard Error 39.9	11.2 10^9 /L Standard Error 65.9	-27.1 10^9 /L Standard Error 0.0
Difference From Baseline for Haematology and Differentials Parameters White blood cell count	-1.1 10^9 /L Standard Error 0.0	-0.7 10^9 /L Standard Error 0.0	0.2 10^9 /L Standard Error 2.9	-0.8 10^9 /L Standard Error 2.6	-0.1 10^9 /L Standard Error 5.6	0.7 10^9 /L Standard Error 2.9	0.0 10^9 /L Standard Error 0.0
Difference From Baseline for Haematology and Differentials Parameters Lymphocytes (N=1,1,4,9,4,17,1)	-0.6 10^9 /L Standard Error 0.0	-0.4 10^9 /L Standard Error 0.0	-0.1 10^9 /L Standard Error 2.0	1.0 10^9 /L Standard Error 1.1	0.0 10^9 /L Standard Error 1.6	0.6 10^9 /L Standard Error 0.6	1.1 10^9 /L Standard Error 0.0
Difference From Baseline for Haematology and Differentials Parameters Neutrophils (N=1,1,4,9,6,17,1)	-4.1 10^9 /L Standard Error 0.0	-4.7 10^9 /L Standard Error 0.0	0.9 10^9 /L Standard Error 3.7	-1.0 10^9 /L Standard Error 5.6	-2.4 10^9 /L Standard Error 10.0	-0.5 10^9 /L Standard Error 3.0	-1.2 10^9 /L Standard Error 0.0

PRIMARY outcome

Timeframe: From signing the informed consent until end of treatment, up to 991 days

Population: Treated set.

Difference from baseline (normalized value) in coagulation parameters Prothrombin time, international normalised ratio (PT-INR) and partial thromboplastin time. Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Difference From Baseline for Coagulation Parameters PT-INR (N=1,1,3,7,5,14,1)	0.1 sec Standard Error 0.0	0.1 sec Standard Error 0.0	0.3 sec Standard Error 0.6	0.1 sec Standard Error 0.1	0.2 sec Standard Error 0.5	-0.0 sec Standard Error 0.1	0.1 sec Standard Error 0.0
Difference From Baseline for Coagulation Parameters Partial thromboplastin time (N=1,1,3,9,4,14,1)	0.7 sec Standard Error 0.0	2.6 sec Standard Error 0.0	-3.6 sec Standard Error 6.7	1.9 sec Standard Error 4.3	1.9 sec Standard Error 4.3	1.5 sec Standard Error 4.7	-2.9 sec Standard Error 0.0

PRIMARY outcome

Timeframe: From signing the informed consent until end of treatment, up to 991 days

Population: Treated set.

Difference from baseline (normalized value). Baseline was defined as the value at the time point closest to but prior to very first administration of trial medication. The standard error is actually the Interquartile Range calculated as P75 minus P25.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Difference From Baseline for Electrolytes Potassium (N=1,1,4,9,6,18,1)	0.2 mmol/L Standard Error 0.0	-0.3 mmol/L Standard Error 0.0	-0.3 mmol/L Standard Error 2.1	0.1 mmol/L Standard Error 0.4	-0.0 mmol/L Standard Error 1.1	0.1 mmol/L Standard Error 0.9	0.0 mmol/L Standard Error 0.0
Difference From Baseline for Electrolytes Sodium (N=1,1,4,9,6,18,1)	2.0 mmol/L Standard Error 0.0	1.0 mmol/L Standard Error 0.0	3.3 mmol/L Standard Error 5.2	0.0 mmol/L Standard Error 1.5	1.5 mmol/L Standard Error 6.0	-1.3 mmol/L Standard Error 5.5	5.0 mmol/L Standard Error 0.0

SECONDARY outcome

Timeframe: From baseline until final follow-up, up to 991 days

Population: Treated set

Clinically relevant abnormalities for Vital Signs (systolic blood pressure, diastolic blood pressure, and pulse rate). New abnormal findings or worsening of baseline conditions were reported as Adverse Events.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Clinically Relevant Abnormalities for Vital Signs	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Just before drug administration every 28±7 days after day 29

Population: Treated set. No descriptive statistics could be calculated for the dosing groups 50 mg and 200 mg QD; 100 mg and 300 mg BID due to insufficient patients.

Cpre,ss represents the pre-dose concentration of Nintedanib in Plasma at steady-state at day 29

Outcome measures

Measure	50mg QD Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=4 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=2 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=7 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID Patients were treated with 300 mg Nintedanib twice daily.
Pre-dose Concentration of Nintedanib in Plasma at Steady-state (Cpre,ss)	—	—	—	7.54 ng/mL Geometric Coefficient of Variation 48.3	11.8 ng/mL Geometric Coefficient of Variation 33.5	11.0 ng/mL Geometric Coefficient of Variation 48.5	—

SECONDARY outcome

Timeframe: Baseline until end of treatment, up to 991 days

Population: Treated set.

Unconfirmed best overall response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0).

PD = Progressive disease.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Unconfirmed Best Overall Response Complete response	0 percentage of participants	100 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Unconfirmed Best Overall Response Partial response	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Unconfirmed Best Overall Response PD or non-evaluable , clinically PD	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	17 percentage of participants	32 percentage of participants	100 percentage of participants
Unconfirmed Best Overall Response Unknown	0 percentage of participants	0 percentage of participants	0 percentage of participants	44 percentage of participants	0 percentage of participants	42 percentage of participants	0 percentage of participants
Unconfirmed Best Overall Response Stable disease	100 percentage of participants	0 percentage of participants	75 percentage of participants	33 percentage of participants	0 percentage of participants	16 percentage of participants	0 percentage of participants
Unconfirmed Best Overall Response Non-evaluable, clinically non-progressive disease	0 percentage of participants	0 percentage of participants	25 percentage of participants	11 percentage of participants	83 percentage of participants	5 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline until end of treatment, up to 991 days

Population: Treated set.

Unconfirmed best objective response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0)

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Unconfirmed Best Objective Response No	100 percentage of participants	0 percentage of participants	100 percentage of participants	56 percentage of participants	100 percentage of participants	53 percentage of participants	100 percentage of participants
Unconfirmed Best Objective Response Yes	0 percentage of participants	100 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	5 percentage of participants	0 percentage of participants
Unconfirmed Best Objective Response Unknown	0 percentage of participants	0 percentage of participants	0 percentage of participants	44 percentage of participants	0 percentage of participants	42 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline until end of treatment, up to 991 days

Population: Treated set.

Clinical benefit was defined as the absence of disease progression (no PD or nonevaluable clinically progressive disease) determined by RECIST (version 1.0).

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Clinical Benefit No	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	11 percentage of participants	0 percentage of participants
Clinical Benefit Yes	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	89 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Baseline until end of treatment, up to 991 days

Population: Treated set.

Confirmed objective response assessed by RECIST (Response Evaluation Criteria In Solid Tumours) criteria (version 1.0)

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Confirmed Objective Response No	100 percentage of participants	0 percentage of participants	100 percentage of participants	56 percentage of participants	100 percentage of participants	58 percentage of participants	100 percentage of participants
Confirmed Objective Response Yes	0 percentage of participants	100 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Confirmed Objective Response Unknown	0 percentage of participants	0 percentage of participants	0 percentage of participants	44 percentage of participants	0 percentage of participants	42 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: First drug administration (in previous trial) until end of treatment, up to 1230 days

Population: Treated set. Data for category

Percentage of participants that experienced progression free survival (PFS), assessed by RECIST (Response Evaluation Criteria In Solid Tumours) (version 1.0), by day 1230. Progression was defined as progressive disease (PD) or non-evaluable clinically progressive disease.

PFS was defined for patients without PD at screening as the time from first treatment with the trial drug in the previous trial until onset of PD or death, whatever comes earlier.

Patients with PD could enter the trial if they showed signs of clinical benefit. For patients with PD at screening, the RECIST assessment at screening was used as a new baseline value and PFS was the time from first treatment with the trial drug in this trial until the onset of progressive disease in this trial or death, whatever comes first.

Outcome measures

Measure	50mg QD n=1 Participants Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 Participants Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 Participants Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 Participants Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 Participants Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 Participants Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 Participants Patients were treated with 300 mg Nintedanib twice daily.
Progression Free Survival Progression (RECIST)	0 percentage of participants	100 percentage of participants	25 percentage of participants	11 percentage of participants	33 percentage of participants	42 percentage of participants	100 percentage of participants
Progression Free Survival Death	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	32 percentage of participants	0 percentage of participants
Progression Free Survival No progressive disease (RECIST) or death	100 percentage of participants	0 percentage of participants	75 percentage of participants	44 percentage of participants	67 percentage of participants	16 percentage of participants	0 percentage of participants
Progression Free Survival Unknown	0 percentage of participants	0 percentage of participants	0 percentage of participants	45 percentage of participants	0 percentage of participants	10 percentage of participants	0 percentage of participants

Adverse Events

50mg QD

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

200mg QD

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

100mg BID

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

150mg BID

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

200mg BID

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

250mg BID

Serious events: 9 serious events

Other events: 17 other events

Deaths: 0 deaths

300mg BID

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	50mg QD n=1 participants at risk Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 participants at risk Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 participants at risk Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 participants at risk Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 participants at risk Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 participants at risk Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 participants at risk Patients were treated with 300 mg Nintedanib twice daily.
Gastrointestinal disorders Constipation	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Ileus	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Subileus	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Vomiting	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Pneumonia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Urinary tract infection	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Osteolysis	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	26.3% 5/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Convulsion	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Sciatica	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Renal and urinary disorders Renal failure	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Renal and urinary disorders Urinary tract obstruction	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days

Other adverse events

Measure	50mg QD n=1 participants at risk Patients were treated with 50 mg Nintedanib once daily in the morning.	200mg QD n=1 participants at risk Patients were treated with 200 mg Nintedanib once daily in the morning.	100mg BID n=4 participants at risk Patients were treated with 100 mg Nintedanib twice daily.	150mg BID n=9 participants at risk Patients were treated with 150 mg Nintedanib twice daily.	200mg BID n=6 participants at risk Patients were treated with 200 mg Nintedanib twice daily.	250mg BID n=19 participants at risk Patients were treated with 250 mg Nintedanib twice daily.	300mg BID n=1 participants at risk Patients were treated with 300 mg Nintedanib twice daily.
Gastrointestinal disorders Abdominal pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	22.2% 2/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	33.3% 2/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Renal and urinary disorders Incontinence	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Renal and urinary disorders Pollakiuria	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Abdominal pain upper	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Constipation	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	15.8% 3/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Diarrhoea	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	66.7% 6/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	83.3% 5/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	63.2% 12/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Dyspepsia	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Flatulence	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Gastric disorder	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Blood and lymphatic system disorders Anaemia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Blood and lymphatic system disorders Lymphopenia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Blood and lymphatic system disorders Neutropenia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Cardiac disorders Arrhythmia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Cardiac disorders Sinus tachycardia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Ear and labyrinth disorders Vertigo	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Eye disorders Conjunctivitis	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Eye disorders Eye disorder	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Eye disorders Eye pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Eye disorders Eyelid oedema	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Eye disorders Visual impairment	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Abdominal distension	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Haemorrhoids	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Nausea	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	33.3% 3/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	66.7% 4/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	31.6% 6/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Tooth discolouration	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Toothache	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Gastrointestinal disorders Vomiting	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	22.2% 2/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	33.3% 2/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
General disorders Adverse drug reaction	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
General disorders Asthenia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	22.2% 2/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	33.3% 2/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	15.8% 3/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
General disorders Chest pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
General disorders Chills	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
General disorders Fatigue	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	55.6% 5/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
General disorders Oedema peripheral	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
General disorders Pyrexia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
General disorders Xerosis	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Hepatobiliary disorders Hepatic pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Immune system disorders Hypersensitivity	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Bronchitis	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Diarrhoea infectious	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Gastrointestinal infection	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Nasopharyngitis	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	33.3% 2/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Parotitis	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Urinary tract infection	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Infections and infestations Viral infection	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Investigations Gamma-glutamyltransferase increased	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Investigations Weight decreased	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	15.8% 3/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Metabolism and nutrition disorders Anorexia	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	26.3% 5/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Metabolism and nutrition disorders Dehydration	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	50.0% 3/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	22.2% 2/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	22.2% 2/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Balance disorder	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Carpal tunnel syndrome	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Dizziness	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	22.2% 2/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Dysgeusia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Headache	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	22.2% 2/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Nervous system disorders Sciatica	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Psychiatric disorders Anxiety	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Psychiatric disorders Insomnia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	10.5% 2/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Renal and urinary disorders Dysuria	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Renal and urinary disorders Haematuria	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Reproductive system and breast disorders Vulvovaginal dryness	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	25.0% 1/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	15.8% 3/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	22.2% 2/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	33.3% 2/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Respiratory, thoracic and mediastinal disorders Rales	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Skin and subcutaneous tissue disorders Hyperhidrosis	100.0% 1/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Skin and subcutaneous tissue disorders Rash	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	16.7% 1/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Vascular disorders Deep vein thrombosis	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Vascular disorders Hot flush	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	11.1% 1/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days
Vascular disorders Phlebitis superficial	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/4 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/9 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/6 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	5.3% 1/19 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 days	0.00% 0/1 • From the first intake of trial medication until 28 days after last intake of medication, up to 1119 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.
• Publication restrictions are in place

Restriction type: OTHER