Trial Outcomes & Findings for LUME-Lung 1: BIBF 1120 Plus Docetaxel as Compared to Placebo Plus Docetaxel in 2nd Line Non Small Cell Lung Cancer (NCT NCT00805194)

NCT ID: NCT00805194

Last Updated: 2018-12-05

Results Overview

Progression Free Survival (PFS) as assessed by central independent review according to the modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) . Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1314 participants
• Primary outcome timeframe: From randomisation until cut-off date 2 November 2010 (when 713 PFS events were observed)
• Results posted on: 2018-12-05

Participant Flow

Participant milestones

Measure	Nintedanib Plus Docetaxel Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Study STARTED	655	659
Overall Study COMPLETED	6	5
Overall Study NOT COMPLETED	649	654

Reasons for withdrawal

Measure	Nintedanib Plus Docetaxel Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Study Progressive disease (modified RECIST)	404	435
Overall Study Worsening or AE of underlying disease	64	70
Overall Study Other AE	84	73
Overall Study Protocol Violation	9	9
Overall Study Lost to Follow-up	5	5
Overall Study Withdrawal by Subject	60	42
Overall Study Not treated	3	4
Overall Study Reasons other than stated above	20	16

Baseline Characteristics

Randomised patients with adenocarcinoma and time since first line therapy.

Baseline characteristics by cohort

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).	Total n=1314 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 9.7 • n=655 Participants	59.8 years STANDARD_DEVIATION 9.0 • n=659 Participants	59.7 years STANDARD_DEVIATION 9.3 • n=1314 Participants
Sex: Female, Male Female	179 Participants n=655 Participants	180 Participants n=659 Participants	359 Participants n=1314 Participants
Sex: Female, Male Male	476 Participants n=655 Participants	479 Participants n=659 Participants	955 Participants n=1314 Participants
Tumour histology Adenocarcinoma	322 Participants n=655 Participants	336 Participants n=659 Participants	658 Participants n=1314 Participants
Tumour histology Squamous cell carcinoma	276 Participants n=655 Participants	279 Participants n=659 Participants	555 Participants n=1314 Participants
Tumour histology Other	57 Participants n=655 Participants	44 Participants n=659 Participants	101 Participants n=1314 Participants
Number of patients with adenocarcinoma and time since first line therapy in categories <9 month	206 Participants n=322 Participants • Randomised patients with adenocarcinoma and time since first line therapy.	199 Participants n=336 Participants • Randomised patients with adenocarcinoma and time since first line therapy.	405 Participants n=658 Participants • Randomised patients with adenocarcinoma and time since first line therapy.
Number of patients with adenocarcinoma and time since first line therapy in categories >=9 month	112 Participants n=322 Participants • Randomised patients with adenocarcinoma and time since first line therapy.	134 Participants n=336 Participants • Randomised patients with adenocarcinoma and time since first line therapy.	246 Participants n=658 Participants • Randomised patients with adenocarcinoma and time since first line therapy.
Number of patients with adenocarcinoma and time since first line therapy in categories Missing	4 Participants n=322 Participants • Randomised patients with adenocarcinoma and time since first line therapy.	3 Participants n=336 Participants • Randomised patients with adenocarcinoma and time since first line therapy.	7 Participants n=658 Participants • Randomised patients with adenocarcinoma and time since first line therapy.

PRIMARY outcome

Timeframe: From randomisation until cut-off date 2 November 2010 (when 713 PFS events were observed)

Population: Randomised Set

Progression Free Survival (PFS) as assessed by central independent review according to the modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) . Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier).

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=565 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=569 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Progression Free Survival (PFS) as Assessed by Central Independent Review	3.4 months Interval 1.5 to 5.7	2.7 months Interval 1.4 to 4.6

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013 (approximately 48 months or 1151 deaths among all patients )

Population: Randomised Set

Overall Survival (OS) defined as the duration from randomisation to death (irrespective of the reason of death). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

A fixed-sequence-testing was implemented for key secondary endpoint if both the primary and the follow-up analysis showed a treatment benefit (P<0.05) of nintedanib over placebo. In this case, the OS would be tested using hierarchical testing of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Survival (Key Secondary Endpoint) All patients	10.1 months Interval 5.0 to 19.4	9.1 months Interval 4.8 to 17.2
Overall Survival (Key Secondary Endpoint) Adenocarcinoma and <9 months	10.9 months Interval 5.1 to 21.9	7.9 months Interval 4.5 to 14.5
Overall Survival (Key Secondary Endpoint) Adenocarcinoma	12.6 months Interval 5.5 to 24.2	10.3 months Interval 5.5 to 19.9

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised Set

Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review	3.5 months Interval 1.5 to 5.7	2.7 months Interval 1.4 to 5.5

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised Set

Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by investigator according to the modified RECIST (version 1.0) criteria.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator	4.2 months Interval 2.1 to 7.1	3.0 months Interval 1.4 to 5.7

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised Set

Confirmed objective response is defined as confirmed Complete Response (CR) and Partial Response (PR) and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Objective Tumour Response investigator assessment	10.4 % of participants	7.6 % of participants
Objective Tumour Response central independent reviewer	4.4 % of participants	3.3 % of participants

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised Set

The duration of objective response is the time from first documented (CR) or (PR) to the time of progression or death and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Duration of Confirmed Objective Tumour Response central independent reviewer	4.3 months Interval 3.0 to 5.7	4.3 months Interval 2.8 to 8.5
Duration of Confirmed Objective Tumour Response investigator assessment	5.7 months Interval 4.1 to 10.0	5.5 months Interval 3.9 to 9.6

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised Set

Time to confirmed objective response is defined as time from randomisation to the date of first documented (CR) or (PR) and evaluated according to the modified RECIST criteria version 1.0.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Time to Confirmed Objective Tumour Response investigator assessment	2.6 months Interval 1.4 to 4.0	2.7 months Interval 1.4 to 4.1
Time to Confirmed Objective Tumour Response central independent reviewer	1.5 months Interval 1.4 to 3.0	2.9 months Interval 1.4 to 5.6

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised Set

Disease control was defined as a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0 for target lesions : Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Disease Control central independent reviewer	54.0 % of participants	41.3 % of participants
Disease Control investigator assessment	63.4 % of participants	51.4 % of participants

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised Set

The duration of disease control was defined as the time from randomisation to the date of disease progression or death (which ever occurs first) for patients with disease control.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Duration of Disease Control central independent reviewer	5.6 months Interval 4.1 to 7.1	5.6 months Interval 4.0 to 8.2
Duration of Disease Control investigator assessment	5.7 months Interval 4.2 to 8.4	5.6 months Interval 4.1 to 8.5

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised Set

Percentage change from baseline in tumour size is defined as decrease in the sum of the longest diameter of the target lesion.

Presented means are in fact adjusted best means percentage changes generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Change From Baseline in Tumour Size central independent reviewer	-4.87 percentage of change in tumor size in mm Interval -6.62 to -3.12	0.58 percentage of change in tumor size in mm Interval -1.19 to 2.35
Change From Baseline in Tumour Size investigator assessment	-10.34 percentage of change in tumor size in mm Interval -12.58 to -8.11	-2.14 percentage of change in tumor size in mm Interval -4.39 to 0.1

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised set

Clinical improvement was defined as the time from randomisation to deterioration in body weight and/or Eastern Cooperative Oncology group performance score (ECOG PS) whichever occurred first.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Clinical Improvement	5.9 months Interval 2.1 to 22.7	5.2 months Interval 2.1 to 19.2

SECONDARY outcome

Timeframe: From randomisation until cut-off date 15 February 2013

Population: Randomised set

Quality of life (QoL) was measured by standardised questionnaires (Health Status Self-Assessment Questionnaire (EQ-5D), EORTC Quality of life questionnaire - Core 30 (EORTC QLQ-C30), Quality of life questionnaire - lung cancer module (EORTC QLQ-LC13). The EORTC QLQ-C30 comprises of 30 questions, using both multi-item scales and single-item measures. EORTC LC-13 comprises of 13 questions incorporating 1 multi-item scale and a series of single items.

The following were the main points of interest:

Time to deterioration of cough (EORTC QLQ-LC13 question 1), Time to deterioration of dyspnoea (QLQ-LC13, composite of questions 3 to 5), Time to deterioration of pain (QLQ- C30, composite of questions 9 and 19).

Time to deterioration of cough, dyspnoea and pain was defined as the time to a 10-point increase from the baseline score.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve

Outcome measures

Measure	Nintedanib Plus Docetaxel n=655 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=659 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Quality of Life (QoL) Time to deterioration of cough	4.3 months Interval 1.6 to 11.8	3.5 months Interval 1.5 to 12.6
Quality of Life (QoL) Time to deterioration of dyspnoea	2.0 months Interval 0.8 to 4.2	2.1 months Interval 0.8 to 4.5
Quality of Life (QoL) Time to deterioration of pain	2.8 months Interval 1.1 to 6.5	2.6 months Interval 0.8 to 5.8

SECONDARY outcome

Timeframe: Before the administration of nintedanib or placebo and between a window of 30 mins to an hour after administration of trial drug during Course 2 and between 1 and 3 hours after administration of trial drug during Course 3

Population: Pharmacokinetic set- all patients in the treated set who were documented to have received at least 1 dose of nintedanib and who had at least 1 valid drug plasma concentration available

Geometric mean of dose normalised predose plasma concentration (Cpre,ss,norm) of nintedanib and of its metabolites BIBF 1202 and BIBF 1202 glucuronide evaluated at steady state based on course 2 and 3. If only one value was available and valid, then this value was used for calculation of Cpre,ss,norm.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=454 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=38 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide nintedanib	0.0707 ng/mL/mg Geometric Coefficient of Variation 77.7	0.106 ng/mL/mg Geometric Coefficient of Variation 52.6
Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide metabolite BIBF 1202	0.0907 ng/mL/mg Geometric Coefficient of Variation 127	0.190 ng/mL/mg Geometric Coefficient of Variation 152
Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide metabolite BIBF 1202 glucuronide	1.04 ng/mL/mg Geometric Coefficient of Variation 153	1.94 ng/mL/mg Geometric Coefficient of Variation 135

SECONDARY outcome

Timeframe: From the first drug administration until 28 days after the last drug administration, up to 42 months

Population: Treated set- all randomised patients who were documented to have taken at least 1 dose of study medication . Patients were allocated to the treatment groups according to the treatment actually received.

Incidence and intensity of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The worst CTCAE grade per patient is reported and MedDRA version 15.1 used.

Serious signs and symptoms of progressive disease were reported as an adverse event in analysis of this endpoint.

Outcome measures

Measure	Nintedanib Plus Docetaxel n=652 Participants Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=655 Participants Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Incidence and Intensity of Adverse Events Grade 5	16.4 % of participants	11.8 % of participants
Incidence and Intensity of Adverse Events Grade 1	5.7 % of participants	8.2 % of participants
Incidence and Intensity of Adverse Events Grade 2	16.6 % of participants	20.5 % of participants
Incidence and Intensity of Adverse Events Grade 3	21.2 % of participants	21.2 % of participants
Incidence and Intensity of Adverse Events Grade 4	33.7 % of participants	31.3 % of participants

Adverse Events

Nintedanib Plus Docetaxel

Serious events: 224 serious events

Other events: 569 other events

Deaths: 107 deaths

Placebo Plus Docetaxel

Serious events: 206 serious events

Other events: 547 other events

Deaths: 77 deaths

Serious adverse events

Measure	Nintedanib Plus Docetaxel n=652 participants at risk Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=655 participants at risk Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Blood and lymphatic system disorders Anaemia	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.92% 6/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Blood and lymphatic system disorders Febrile neutropenia	4.6% 30/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	2.9% 19/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Blood and lymphatic system disorders Leukopenia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Blood and lymphatic system disorders Neutropenia	3.2% 21/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	3.2% 21/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Blood and lymphatic system disorders Pancytopenia	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Acute myocardial infarction	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Angina pectoris	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Atrial fibrillation	0.77% 5/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Atrial flutter	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Atrioventricular block second degree	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Cardiac arrest	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Cardiac failure	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Cardiac failure acute	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Cardio-respiratory arrest	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Cardiopulmonary failure	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Coronary artery disease	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Myocardial infarction	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Pericardial effusion	0.61% 4/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Pericarditis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Tachyarrhythmia	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Cardiac disorders Ventricular arrhythmia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Ear and labyrinth disorders Vertigo	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Eye disorders Diplopia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Abdominal pain	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.61% 4/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Diarrhoea	2.5% 16/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	2.0% 13/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Diverticulum intestinal	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Dysphagia	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Enteritis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Gastric perforation	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Gastritis erosive	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Gastrointestinal necrosis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Haematochezia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Intestinal obstruction	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Intestinal perforation	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Large intestine perforation	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Nausea	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Neutropenic colitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Pancreatitis	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Pancreatitis acute	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Stomatitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Vomiting	1.2% 8/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	1.1% 7/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Asthenia	1.1% 7/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.61% 4/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Chest discomfort	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Chest pain	1.1% 7/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	1.2% 8/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Condition aggravated	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Death	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Device occlusion	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Extravasation	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Fatigue	1.1% 7/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Feeling abnormal	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders General physical health deterioration	1.7% 11/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	1.2% 8/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Malaise	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Mucosal inflammation	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Multi-organ failure	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Oedema peripheral	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Organ failure	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Pain	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Performance status decreased	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Pyrexia	1.1% 7/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	1.4% 9/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Hepatobiliary disorders Bile duct obstruction	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Hepatobiliary disorders Cholecystocholangitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Hepatobiliary disorders Cholestasis	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Hepatobiliary disorders Hepatic failure	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Hepatobiliary disorders Hepatic function abnormal	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Hepatobiliary disorders Jaundice cholestatic	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Immune system disorders Drug hypersensitivity	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Immune system disorders Hypersensitivity	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Abscess rupture	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Appendicitis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Bronchitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.61% 4/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Bronchopneumonia	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Cellulitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Empyema	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Erysipelas	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Febrile infection	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Folliculitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Gastroenteritis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Gastrointestinal infection	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations H1N1 influenza	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Infection	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Infectious pleural effusion	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Influenza	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Laryngitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Lower respiratory tract infection	0.61% 4/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Lung abscess	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Lung infection	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Neutropenic infection	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Neutropenic sepsis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Opportunistic infection	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Oral candidiasis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Perirectal abscess	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Pharyngitis	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Pneumonia	2.6% 17/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	4.0% 26/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Pulmonary tuberculosis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Respiratory tract infection	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Respiratory tract infection bacterial	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Sepsis	1.1% 7/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Septic shock	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Streptococcal infection	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Tuberculosis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Upper respiratory tract infection	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Infections and infestations Urinary tract infection	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Injury, poisoning and procedural complications Acetabulum fracture	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Injury, poisoning and procedural complications Femoral neck fracture	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Injury, poisoning and procedural complications Spinal compression fracture	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Alanine aminotransferase increased	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Aspartate aminotransferase increased	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Blood creatinine increased	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Haemoglobin decreased	0.46% 3/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Hepatic enzyme increased	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Liver function test abnormal	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Neutrophil count decreased	0.92% 6/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Weight decreased	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations White blood cell count decreased	0.46% 3/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Decreased appetite	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Dehydration	0.77% 5/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Hypercalcaemia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Hyperglycaemia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Hyperuricaemia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Hypoalbuminaemia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Hypoglycaemia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Hypokalaemia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Hyponatraemia	0.61% 4/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Back pain	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Flank pain	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Muscular weakness	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Pain in extremity	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Pathological fracture	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer metastatic	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	3.8% 25/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	2.6% 17/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to chest wall	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to kidney	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.46% 3/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to skin	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Aphasia	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Brain oedema	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Cerebral infarction	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Cerebrovascular accident	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Cognitive disorder	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Coma	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Convulsion	0.61% 4/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Depressed level of consciousness	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Diplegia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Dizziness	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Encephalopathy	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Epiduritis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Facial paresis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Headache	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Hemiplegia	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Hypoaesthesia	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Intracranial pressure increased	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Ischaemic stroke	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Lethargy	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Loss of consciousness	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Monoparesis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Nervous system disorder	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Neuralgia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Neuropathy peripheral	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Paraesthesia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Paraparesis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Restless legs syndrome	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Spinal cord compression	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Syncope	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Transient ischaemic attack	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Psychiatric disorders Confusional state	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Psychiatric disorders Depression	0.61% 4/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Psychiatric disorders Disorientation	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Psychiatric disorders Mental disorder due to a general medical condition	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Psychiatric disorders Panic attack	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Psychiatric disorders Personality change	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Psychiatric disorders Psychotic disorder	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Renal and urinary disorders Bladder perforation	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Renal and urinary disorders Haematuria	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Renal and urinary disorders Renal failure acute	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Renal and urinary disorders Urinary incontinence	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Renal and urinary disorders Urinary retention	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.46% 3/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Alveolitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.31% 2/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Bronchial haemorrhage	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Bronchial secretion retention	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Bronchostenosis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Cough	0.46% 3/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 24/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	4.6% 30/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.92% 6/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	1.1% 7/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 8/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	1.2% 8/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.46% 3/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.61% 4/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.92% 6/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.77% 5/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.46% 3/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Respiratory depression	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.2% 8/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Stridor	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Tracheal stenosis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Circulatory collapse	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Deep vein thrombosis	0.46% 3/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Haemorrhage	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.31% 2/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Hypotension	0.46% 3/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Peripheral ischaemia	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Subclavian artery thrombosis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Superior vena cava syndrome	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Thrombosis	0.00% 0/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.15% 1/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Venous thrombosis	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Vascular disorders Venous thrombosis limb	0.15% 1/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	0.00% 0/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.

Other adverse events

Measure	Nintedanib Plus Docetaxel n=652 participants at risk Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).	Placebo Plus Docetaxel n=655 participants at risk Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Blood and lymphatic system disorders Anaemia	5.1% 33/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	6.6% 43/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Blood and lymphatic system disorders Neutropenia	10.6% 69/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	11.1% 73/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Abdominal pain	5.4% 35/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	5.6% 37/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Constipation	5.4% 35/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	11.6% 76/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Diarrhoea	39.9% 260/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	19.8% 130/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Nausea	24.2% 158/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	17.9% 117/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Stomatitis	9.5% 62/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	8.2% 54/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Gastrointestinal disorders Vomiting	15.6% 102/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	8.2% 54/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Asthenia	7.8% 51/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	9.2% 60/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Chest pain	7.5% 49/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	8.2% 54/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Fatigue	29.3% 191/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	26.7% 175/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Oedema peripheral	5.4% 35/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	6.4% 42/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
General disorders Pyrexia	11.7% 76/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	13.6% 89/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Alanine aminotransferase increased	28.2% 184/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	8.4% 55/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Aspartate aminotransferase increased	22.2% 145/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	6.6% 43/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Blood alkaline phosphatase increased	5.8% 38/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	1.4% 9/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Haemoglobin decreased	10.7% 70/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	11.8% 77/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations Neutrophil count decreased	36.2% 236/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	35.4% 232/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Investigations White blood cell count decreased	24.1% 157/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	24.1% 158/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Metabolism and nutrition disorders Decreased appetite	22.1% 144/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	15.4% 101/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 40/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	7.0% 46/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Back pain	4.0% 26/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	6.7% 44/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Myalgia	6.1% 40/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	6.9% 45/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Musculoskeletal and connective tissue disorders Pain in extremity	4.8% 31/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	6.3% 41/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Dizziness	4.8% 31/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	5.2% 34/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Dysgeusia	4.8% 31/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	5.2% 34/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Headache	6.0% 39/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	6.4% 42/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Nervous system disorders Peripheral sensory neuropathy	6.1% 40/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	7.2% 47/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Psychiatric disorders Insomnia	4.8% 31/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	5.8% 38/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Cough	14.7% 96/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	16.5% 108/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.3% 100/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	12.2% 80/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
Skin and subcutaneous tissue disorders Alopecia	16.4% 107/652 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.	18.2% 119/655 • From the first drug administration until 28 days after the last drug administration, up to 42 months Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.

Additional Information

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