Compare Safety and Efficacy of BIBF 1120 Versus Sunitinib.

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01024920
• Collaborator: (none)
• Enrollment: 99
• Locations: 15
• Arms: 2
• Duration (Months): 126.1
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Compare safety and efficacy of BIBF 1120 versus sunitinib in patients with advanced RCC and to investigate the effects of BIBF 1120 on the heart rate (HR) corrected QT interval (QTcF).

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell	Drug: BIBF 1120; Drug: sunitinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Open Label, Parallel Group Phase II Study Comparing the Efficacy and Tolerability of BIBF 1120 Versus Sunitinib in Previously Untreated Patients With Renal Cell Cancer
• Study Start Date: Dec 16, 2009
• Actual Primary Completion Date: Nov 8, 2011
• Actual Study Completion Date: Jun 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nintedanib (BIBF 1120) Non-marketed substance: Twice daily oral doses of 200mg BIBF 1120 given continuously.	Drug: BIBF 1120; VEGF inhibitor
Active Comparator: sunitinib Marketed substance: Once a day oral doses of 50mg sunitinib given in repeated 6 week cycles: 4 weeks active, 2 weeks rest.	Drug: sunitinib; VEGF inhibitor

Outcome Measures

Primary Outcome Measures

1. Probability Rates of Progression-free Survival at 9 Months [At 9 months after randomisation.]

   Progression free survival rate at 9 months is the estimated probability of being alive and not having progressive disease at 9 months after randomisation. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria version 1.1 (RECIST v1.1), at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started together with an absolute increase in the sum of the longest diameters of at least 5 mm, or the appearance of one or more new lesions. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication.

2. Time-matched Change From Baseline to Day 15 in QTcF (QT Interval Corrected by the Fridericia Formula) at 0 Hour (h), at 1 h, at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120) [At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.]

   QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate by the Fridericia formula. Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 15 in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 15 obtained at time t minus baseline QTcF measurement at time t. 0 h is 5 min prior to dosing on Day 15. Time-matched change from baseline to Day 15 in QTcF was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 0 h,1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib on Day 15 of are reported.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [From the start of study until the cut-off date for 3 year efficacy analysis, up to 3 years.]

   Progression free survival (PFS) from randomisation to the occurrence of disease progression (by RECIST Version 1.1) or death, whichever occurred first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started together with an absolute increase in the sum of the longest diameters of at least 5 mm, or the appearance of one or more new lesions. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication. The Kaplan-Meier method was used to calculate the estimates.

2. Objective Response According to RECIST Criteria [From the start of study until the cut-off date for 3 year efficacy analysis, up to 3 years.]

   Objective response was defined as complete response (CR, the disappearance of all target and non-target lesions and no new lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of the longest diameters and no new lesions) as determined by RECIST Version 1.1. Numbers of participants with objective response are reported. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication.

3. Duration of Objective Response [From the time of first objective response to the time of disease progression or death (whichever comes first), up to 3 years.]

   Duration (months) of objective response was measured from the time of first objective response to the time of disease progression (by RECIST Version 1.1) or death, whichever occurred first. Objective response was defined as complete response (CR, the disappearance of all target and non-target lesions and no new lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of the longest diameters and no new lesions) as determined by RECIST Version 1.1. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication. The Kaplan-Meier method was used to calculate the estimates.

4. Overall Survival [From randomisation to death, up to 3 years.]

   Overall survival was calculated as the time (months) from randomisation to death. Patients for whom there was no evidence of death at the time of analysis were censored on the date that they were last known to have been alive. The Kaplan-Meier method was used to calculate the estimates.

5. Time to Progression [From randomisation up to objective tumour progression, up to 3 years.]

   Time to progression is defined as the time period from randomisation to objective tumour progression. Patients with no progression (by RECIST Version 1.1) were censored at the date of the last evaluable imaging. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started together with an absolute increase in the sum of the longest diameters of at least 5 mm, or the appearance of one or more new lesions. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication. The Kaplan-Meier method was used to calculate the estimates.

6. Time to Treatment Failure [From randomisation up to objective tumour progression, up to 3 years.]

   Time to treatment failure was defined as the time from randomisation to objective tumour progression (by RECIST Version 1.1), death, global deterioration of health status requiring treatment discontinuation, or start of new anticancer treatment, whichever came first. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication.The Kaplan-Meier method was used to calculate the estimates.

7. Time-matched Change From Baseline to Day 1 in QTcF (QT Interval Corrected by the Fridericia Formula) at 1 Hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120) [At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 of treatment Cycle 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.]

   QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate by the Fridericia formula. Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 1 obtained at time t minus baseline QTcF measurement at time t. Time-matched change from baseline to Day 1 in QTcF was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib on Day 1 are reported.

8. Time-matched Change From Baseline in QTcF Interval (QT Interval Corrected by the Fridericia Formula) at the Time of Each Participant's Maximum Plasma Concentration of Nintedanib (BIBF 1120), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

   QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QTcF measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QTcF' at the time of the participant's maximum nintedanib plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

9. Time-Matched Change From Baseline in QTcF Interval at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202 (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

   Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QTcF measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QTcF' at the time of the participant's maximum BIBF 1202 (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

10. Time-Matched Change From Baseline in QTcF Interval at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202-glucuronide (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QTcF measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QTcF' at the time of the participant's maximum BIBF 1202-glucuronide (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline values were taken at exactly the same time points as on Day 15.

11. Average Time-matched Changes From Baseline in QTcF Interval Over 1 h to 12 h After Dosing on Days 1 and 15 of Treatment Cycle 1 [At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.]

    Average time-matched in QTcF interval (QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula) changes over 1 to 12 hours was evaluated using a t-test for paired observation. The mean differences between post-treatment values (Days 1 and 15) and baseline (Day -1) along with two-sided 90% confidence limits are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.

12. Time-matched Changes From Baseline to Day 15 in QT Interval at 0 Hour (h), at 1 h, at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120) [At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.]

    QT interval is the electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 15 in QT at time t was defined as the QT measurement following administration of nintedanib on Day 15 obtained at time t minus baseline QT measurement at time t. 0 h is 5 min prior to dosing on Day 15. Time-matched change from baseline to Day 15 in QT was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib on Day 15 of Cycle 1are reported.

13. Time-matched Changes From Baseline to Day 1 in QT Interval at 1 Hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120) [At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.]

    QT interval is the electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 in QT at time t was defined as the QT measurement following administration of nintedanib on Day 1 obtained at time t minus baseline QT measurement at time t. Time-matched change from baseline to Day 1 in QT was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib on Day 1 are reported.

14. Time-Matched Change From Baseline in QT Interval at the Time of Each Patient's Maximum Plasma Concentration of Nintedanib (BIBF 1120), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    QT interval is the (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QT at time t was defined as the QT measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QT measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QT' at the time of the participant's maximum nintedanib plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.

15. Time-Matched Change From Baseline in QT Interval at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202 (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.]

    QT interval is the (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QT at time t was defined as the QT measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QT measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QT' at the time of the participant's maximum BIBF 1202 (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

16. Time-Matched Change From Baseline in QT Interval at the Time of Each Patient's Maximum Plasma Concentration BIBF 1202-glucuronide (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    QT interval is the (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QT at time t was defined as the QT measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QT measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QT' at the time of the participant's maximum BIBF 1202-glucuronide (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

17. Averaged Time-matched Changes From Baseline in QT Interval (Electrocardiogram (ECG) Interval From the Beginning of the QRS Complex to the End of the T Wave) Over 1 h to 12 h After Dosing on Days 1 and 15 of Treatment Cycle 1 [At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle.]

    Averaged time-matched QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) changes from baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120) to Day 1 (first drug dose nintedanib (BIBF 1120)) and to Day 15 (steady state) over 1 to 12 hours was evaluated using a t-test for paired observation. The mean differences between post-treatment values (Days 1 and 15) and baseline (Day -1) along with two-sided 90% confidence limits are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.

18. Time-Matched Heart Rate (HR) Changes From Baseline to Day 15 at 0 Hour (h), at 1 h, at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120) [At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.]

    Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib (BIBF 1120) at time t. Time-matched change from baseline to Day 15 in HR at time t was defined as the HR measurement following administration of nintedanib (BIBF 1120) on Day 15 obtained at time t minus baseline HR measurement at time t. 0 h is 5 min prior to dosing on Day 15. Time-matched change from baseline to Day 15 in HR was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib (BIBF 1120) on Day 15 of Cycle 1 are reported.

19. Time-Matched Heart Rate (HR) Changes From Baseline to Day 1 at 1 Hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120) [At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.]

    Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib (BIBF 1120) at time t. Time-matched change from baseline to Day 1 in HR at time t was defined as the HR measurement following administration of nintedanib (BIBF 1120) on Day 1 obtained at time t minus baseline HR measurement at time t. Time-matched change from baseline to Day 1 in HR was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib (BIBF 1120) on Day 1 are reported.

20. Time-Matched Change From Baseline in Heart Rate (HR) at the Time of Each Patient's Maximum Nintedanib (BIBF 1120) Plasma Concentration, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in HR at time t was defined as the HR measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline HR measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in HR' at the time of the participant's maximum nintedanib plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

21. Time-Matched Change From Baseline in Heart Rate (HR) at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202 (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in HR at time t was defined as the HR measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline HR measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in HR' at the time of the participant's maximum BIBF 1202 (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

22. Time-Matched Change From Baseline in Heart Rate (HR) at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202-glucuronide (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of treatment cycle 1. Continues in the description.]

    Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in HR at time t was defined as the HR measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline HR measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in HR' at the time of the participant's maximum BIBF 1202-glucuronide (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.

23. Averaged Time-Matched Heart Rate (HR) Change From Baseline Over 1 to 12 Hours, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15.]

    Averaged time-matched heart rate changes from baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) to Day 1 (first drug dose nintedanib (BIBF 1120)) and to Day 15 (steady state) over 1 to 12 hours was evaluated using a t-test for paired observation. The mean differences between post-treatment values (Days 1 and 15) and baseline (Day -1) along with two-sided 90% confidence limits are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.

24. Frequency of Patients With Maximum Time-Matched QTcF Interval Change From Baseline Categorized by Magnitude of Change, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of patients with maximum time-matched change from baseline in the QTcF interval observed at each point in time, i.e., 9 time points on Day 1 and 10 timepoints on Day 15 is reported. 3 categories of individual QTcF increases from baseline to maximum value were defined: <= 30 milliseconds (ms) > 30 to 60 milliseconds (ms) > 60 milliseconds (ms) Changes more than 60 ms in the QTcF interval represent notable changes. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

25. Frequency of Patients With Maximum Time-Matched QT Interval (Electrocardiogram (ECG) Interval From the Beginning of the QRS Complex to the End of the T Wave) Change From Baseline Categorized by Magnitude of Change, Days 1 and 15 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    Number of patients with maximum time-matched change from baseline in the QT interval observed at each point in time, i.e., 9 time points on Day 1 and 10 timepoints on Day 15 is reported. 3 categories of individual QTcF increases from baseline to maximum value were defined: <= 30 milliseconds (ms) > 30 to 60 milliseconds (ms) > 60 milliseconds (ms) Changes more than 60 ms in the QT interval represent notable changes. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

26. Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF ≤450 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of participants with new onset (not present at any time pre-dose) of QTcF ≤450 milliseconds (ms) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

27. Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF >450 to 470 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.]

    QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of participants with new onset of QTcF >450 to 470 milliseconds (ms) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

28. Number of Participants With New Onset of QTcF> 470 to 500 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.]

    QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of participants with new onset of QTcF> 470 to 500 milliseconds (ms) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

29. Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF> 500 Milliseconds (ms) (Notable Prolongation), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.]

    QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of participants with new onset of QTcF> 500 milliseconds (ms) (notable prolongation) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

30. Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QT (Electrocardiogram (ECG) Interval From the Beginning of the QRS Complex to the End of the T Wave) > 500 ms (Notable Prolongation), Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.]

    Number of participants with new onset of QT (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave)> 500 milliseconds (ms) (notable prolongation) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

31. Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval [At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.]

    The PR interval is an electrocardiogram (ECG) interval and is the time from the onset of the P wave to the start of the QRS complex (combination of the Q wave, R wave and S wave). It reflects conduction through the atrioventricular node (AV) node. The normal PR interval is between 120 - 200 milliseconds (ms) (0.12-0.20s) in duration. Absolute values at baseline (Day-1 prior to the first dosing of nintedanib) and at Day 1 (first drug dose of nintedanib (BIBF 1120)) and changes from baseline to Day 1 at each point in time i.e., 10 time points from 0 to 12 in the PR interval are reported.

32. Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval [At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.]

    The PR interval is an electrocardiogram (ECG) interval and is the time from the onset of the P wave to the start of the QRS complex (combination of the Q wave, R wave and S wave). It reflects conduction through the atrioventricular node (AV) node. The normal PR interval is between 120 - 200 milliseconds (ms) (0.12-0.20s) in duration. Absolute values at baseline (Day-1 prior to the first dosing of nintedanib (BIBF 1120) and at Day 15 (steady state) and changes from baseline to Day 15 at each point in time i.e., 10 time points from 0 to 12 in the PR interval are reported.

33. Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval [At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.]

    QRS interval is an electrocardiogram (ECG) interval and is the time interval from the onset to the end of the QRS complex (combination of the Q wave, R wave and S wave). The normal QRS duration is less than 120 milliseconds (ms). Absolute values and changes from baseline (Day-1 prior to the first dosing of nintedanib) to Day 1 (first drug dose of nintedanib (BIBF 1120)) at each point in time i.e., 10 time points from 0 to 12 in the QRS interval are reported.

34. Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval [At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.]

    QRS interval is an electrocardiogram (ECG) interval and is the time interval from the onset to the end of the QRS complex (combination of the Q wave, R wave and S wave). The normal QRS duration is less than 120 milliseconds (ms). Absolute values and changes from baseline (Day-1 prior to the first dosing of nintedanib) to Day 15 (steady state) at each point in time i.e., 10 time points from 0 to 12 in the QRS interval are reported.

35. Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 [At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.]

    Based on the interpretation of the electrocardiogram (ECG) patients were classified in 3 categories: Normal (a normal ECG reading would be a reading that includes the following normal findings: 1) normal general features; 2) no arrhythmia; 3) no conduction delays; 4) T-wave morphology of normal; and 5) normal U-wave morphology) on Day 1 or on Day 15) Not normal and not normal at baseline (an abnormal ECG reading would be a reading that includes one or more of the following abnormal findings: 1) abnormal general features; 2) arrhythmia; 3) conduction delays; 4) T-wave morphology of flat, inverted or biphasic; and 5) abnormal U-wave morphology) on Day 1 or on Day 15) Not normal and new onset of finding; Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

36. Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 [From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.]

    The number of participants who experienced adverse events graded according to NCI CTCAE version 3.0, is reported below.The maximum grade of adverse event intensity for each type of treatment-related adverse event was recorded for each patient. Grade 1 - Mild AE Grade 2 - Moderate AE Grade 3 - Severe AE Grade 4 - Life-threatening or disabling AE Grade 5 - Death related to AE

37. Number of Participants With Adverse Events Leading to Dose Reduction [From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.]

    Number of participants who experienced Adverse Events which led to dose reduction of the trial medication is reported for each treatment arm.

38. Number of Participants With Adverse Events Leading to Discontinuation of Trial Drug [From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.]

    Number of participants with Adverse Events which lead to discontinuation of trial medication drug is reported for each treatment arm.

39. Number of Participants With Adverse Events Requiring or Prolonging Hospitalisation [From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.]

    Number of participants who experienced Adverse Events which required or prolonged hospitalisation of patients is reported for each treatment arm.

40. Duration of Hospital Stays Due to Adverse Events Requiring or Prolonging Hospitalisation [From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.]

    Duration of hospitalisation in days for each treatment arm is reported for those patients who experienced adverse events which required or prolonged hospitalisation (of the patients).

41. Frequency of Patients With Possible Clinically Significant Abnormal Lab Values [From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.]

    Number of patients with possible clinically significant abnormal lab values for the lab parameters alkaline phosphatase, activated partial thromboplastin time (APTT), creatinine, haemoglobin, prothrombin time (PT)-international normalized ratio (INR), potassium, lymphocytes, sodium, neutrophils, platelets, aspartate amino transferase (AST), alanine aminotransferase (ALT), bilirubin and white blood cell count is reported. Only lab values with CTCAE rule for possible clinical significance are displayed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Patients with unresectable or metastatic Renal Cell Cancer, who have received no previous systemic anti-cancer treatment.

2. Histological-confirmed diagnosis of renal cell cancer with clear cell component.

3. Acceptable renal,liver,cardiovascular,bone marrow and other functions to allow sunitinib/BIBF 1120 treatment.

Exclusion criteria:

1. Patients unable to tolerate Sunitinib/BIBF 1120 treatment

2. Treatment with other investigational drugs or participation in another clinical study within the past 4 weeks before start of therapy or concomitantly with this study.

3. Patients unable to comply with the 1199.26 protocol.

4. Pregnancy or breast feeding.

5. Active alcohol or drug abuse.

6. Women of child bearing potential, or men who are able to father a child, unwilling to use a medically acceptable form of contraception during the study period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pecs Medical School, Dept. of Oncotherapy	Pecs		Hungary	7624
2	Ziemia Lubelska Oncological Center, Lublin	Lublin		Poland	20-099
3	Onco.Cent. - Instit. of Maria Sklodowskiej-Curie	Warszawa		Poland	02-781
4	Military Central Clinical Emergency Hospital	Bucharest		Romania	010825
5	Sf. Nectarie Oncology Center, Craiova	Craiova		Romania	200347
6	ONCOLAB SRL, Craiova	Craiova		Romania	200385
7	Municipal Establishment Cherkasy Oncology Centre	Cherkasy		Ukraine	18009
8	Bukovynsk State Medical University	Chernivtsi		Ukraine	58013
9	Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council	Dnipropetrovks		Ukraine	49102
10	CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.	Lviv		Ukraine	79031
11	Uzhgorod National University, Oncology Centre	Uzhgorod		Ukraine	88000
12	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ
13	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
14	Surrey Cancer Research Institute	Guildford		United Kingdom	GU2 7WG
15	St James's University Hospital	Leeds		United Kingdom	LS9 7TF

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01024920
• Other Study ID Numbers: 1199.26; 2009-009516-44
• First Posted: Dec 3, 2009
• Last Update Posted: Jul 19, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Carcinoma, Renal Cell; Sunitinib; Nintedanib

Study Results

Participant Flow

Recruitment Details	An open-label, 2:1 randomised, parallel-arm comparison of nintedanib versus sunitinib in patients with advanced renal cell cancer (RCC) who had not received prior systemic therapy.
Pre-assignment Detail	All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Period Title: Overall Study
STARTED	67	32
Treated	64	32
COMPLETED	0	0
NOT COMPLETED	67	32

Baseline Characteristics

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib	Total
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.	Total of all reporting groups
Overall Participants	64	32	96
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.4 (9.7)	55.5 (11.4)	58.8 (10.5)
Sex: Female, Male (Count of Participants)
Female	20 31.3%	10 31.3%	30 31.3%
Male	44 68.8%	22 68.8%	66 68.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	64 100%	32 100%	96 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
QTcF interval baseline values (millisecconds (ms)) [Mean (Standard Deviation) ]
-5 minutes	405.2 (19.6)	405.2 (19.6)
1 hour (h)	406.0 (20.3)	406.0 (20.3)
2 h	405.3 (19.4)	405.3 (19.4)
3 h	406.7 (19.4)	406.7 (19.4)
4 h	407.0 (17.8)	407.0 (17.8)
5 h	407.2 (18.0)	407.2 (18.0)
6 h	405.9 (18.3)	405.9 (18.3)
7 h	405.4 (19.2)	405.4 (19.2)
10 h	406.6 (19.2)	406.6 (19.2)
12 h	406.0 (19.2)	406.0 (19.2)

Outcome Measures

1. Primary Outcome

Title	Probability Rates of Progression-free Survival at 9 Months
Description	Progression free survival rate at 9 months is the estimated probability of being alive and not having progressive disease at 9 months after randomisation. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria version 1.1 (RECIST v1.1), at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started together with an absolute increase in the sum of the longest diameters of at least 5 mm, or the appearance of one or more new lesions. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication.
Time Frame	At 9 months after randomisation.

Outcome Measure Data

Analysis Population Description

Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Number (95% Confidence Interval) [Probability]	0.431	0.452

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib (BIBF 1120), Sunitinib
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8531
	Comments	P-value for comparison of Kaplan-Meier estimates at 9 months using normal approximation test (two-sided).
	Method	Normal approximation test
	Comments

2. Primary Outcome

Title	Time-matched Change From Baseline to Day 15 in QTcF (QT Interval Corrected by the Fridericia Formula) at 0 Hour (h), at 1 h, at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)
Description	QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate by the Fridericia formula. Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 15 in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 15 obtained at time t minus baseline QTcF measurement at time t. 0 h is 5 min prior to dosing on Day 15. Time-matched change from baseline to Day 15 in QTcF was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 0 h,1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib on Day 15 of are reported.
Time Frame	At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex (Q, R and S wave) to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline to Day 15 at -5 minutes (min)	2.6
Time-matched change from baseline to Day 15 at 1 hour (h)	0.4
Time-matched change from baseline to Day 15 at 2 h	-1.7
Time-matched change from baseline to Day 15 at 3 h	-0.5
Time-matched change from baseline to Day 15 at 4 h	-0.5
Time-matched change from baseline to Day 15 at 5 h	0.3
Time-matched change from baseline to Day 15 at 6 h	2.2
Time-matched change from baseline to Day 15 at 7 h	3.1
Time-matched change from baseline to Day 15 at 10 h	0.1
Time-matched change from baseline to Day 15 at 12 h	1.6

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression free survival (PFS) from randomisation to the occurrence of disease progression (by RECIST Version 1.1) or death, whichever occurred first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started together with an absolute increase in the sum of the longest diameters of at least 5 mm, or the appearance of one or more new lesions. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication. The Kaplan-Meier method was used to calculate the estimates.
Time Frame	From the start of study until the cut-off date for 3 year efficacy analysis, up to 3 years.

Outcome Measure Data

Analysis Population Description

Treated set: all patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Median (95% Confidence Interval) [Months]	8.44	8.38

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib (BIBF 1120), Sunitinib
	Comments	A stratified log-rank test (two-sided, 0.05 significance level) was used to test the effect of nintedanib on PFS compared with sunitinib. The test was stratified by Motzer risk score category (low/intermediate or high) and prior nephrectomy surgery for Renal Cell Cancer (yes or no).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6395
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.120
	Confidence Interval	(2-Sided) 95%; 0.697 to 1.800
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio from Cox proportional hazards model stratified by Motzer risk score and previous surgery.

4. Secondary Outcome

Title	Objective Response According to RECIST Criteria
Description	Objective response was defined as complete response (CR, the disappearance of all target and non-target lesions and no new lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of the longest diameters and no new lesions) as determined by RECIST Version 1.1. Numbers of participants with objective response are reported. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication.
Time Frame	From the start of study until the cut-off date for 3 year efficacy analysis, up to 3 years.

Outcome Measure Data

Analysis Population Description

Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Complete Response	0 0%	1 3.1%
Partial response	14 21.9%	11 34.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib (BIBF 1120), Sunitinib
	Comments	A logistic regression model stratified by Motzer risk score category and prior surgery for renal cell cancer (RCC) was used to compare the objective response rate between the two treatment arms. The corresponding odds ratio and 95% Confidence Intervals was also presented.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1213
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.484
	Confidence Interval	(2-Sided) 95%; 0.193 to 1.212
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio > 1 favours nintedanib.

5. Secondary Outcome

Title	Duration of Objective Response
Description	Duration (months) of objective response was measured from the time of first objective response to the time of disease progression (by RECIST Version 1.1) or death, whichever occurred first. Objective response was defined as complete response (CR, the disappearance of all target and non-target lesions and no new lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of the longest diameters and no new lesions) as determined by RECIST Version 1.1. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication. The Kaplan-Meier method was used to calculate the estimates.
Time Frame	From the time of first objective response to the time of disease progression or death (whichever comes first), up to 3 years.

Outcome Measure Data

Analysis Population Description

Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment and showed objective response.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	14	12
Median (Inter-Quartile Range) [Months]	19.42	11.66

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival was calculated as the time (months) from randomisation to death. Patients for whom there was no evidence of death at the time of analysis were censored on the date that they were last known to have been alive. The Kaplan-Meier method was used to calculate the estimates.
Time Frame	From randomisation to death, up to 3 years.

Outcome Measure Data

Analysis Population Description

Treated Set (TS) : All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Median (95% Confidence Interval) [Months]	20.37	21.22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib (BIBF 1120), Sunitinib
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7593
	Comments	P-value from log-rank stratified by Motzer risk score and previous surgery.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.920
	Confidence Interval	(2-Sided) 95%; 0.542 to 1.564
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio from Cox proportional hazards model stratified by Motzer risk score and previous surgery. Hazard ratio < 1 favours nintedanib.

7. Secondary Outcome

Title	Time to Progression
Description	Time to progression is defined as the time period from randomisation to objective tumour progression. Patients with no progression (by RECIST Version 1.1) were censored at the date of the last evaluable imaging. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started together with an absolute increase in the sum of the longest diameters of at least 5 mm, or the appearance of one or more new lesions. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication. The Kaplan-Meier method was used to calculate the estimates.
Time Frame	From randomisation up to objective tumour progression, up to 3 years.

Outcome Measure Data

Analysis Population Description

Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Median (95% Confidence Interval) [Months]	8.48	8.54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib (BIBF 1120), Sunitinib
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5958
	Comments
	Method	Log Rank
	Comments	P-value from log-rank stratified by Motzer risk score and previous surgery.
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.143
	Confidence Interval	(2-Sided) 95%; 0.697 to 1.873
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio from Cox proportional hazards model stratified by Motzer risk score and previous surgery. Hazard ratio < 1 favours nintedanib.

8. Secondary Outcome

Title	Time to Treatment Failure
Description	Time to treatment failure was defined as the time from randomisation to objective tumour progression (by RECIST Version 1.1), death, global deterioration of health status requiring treatment discontinuation, or start of new anticancer treatment, whichever came first. Tumour imaging was made by investigators using Computed tomography (CT)/Magnetic Resonance imaging (MRI) every 12 weeks after the first administration of the trial medication.The Kaplan-Meier method was used to calculate the estimates.
Time Frame	From randomisation up to objective tumour progression, up to 3 years.

Outcome Measure Data

Analysis Population Description

Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Median (95% Confidence Interval) [Month]	8.44	8.36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib (BIBF 1120), Sunitinib
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5712
	Comments
	Method	Log Rank
	Comments	P-value from log-rank stratified by Motzer risk score and previous surgery (two-sided).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.142
	Confidence Interval	(2-Sided) 95%; 0.720 to 1.812
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio from Cox proportional hazards model stratified by Motzer risk score and previous surgery. Hazard ratio < 1 favours nintedanib.

9. Secondary Outcome

Title	Time-matched Change From Baseline to Day 1 in QTcF (QT Interval Corrected by the Fridericia Formula) at 1 Hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)
Description	QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate by the Fridericia formula. Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 1 obtained at time t minus baseline QTcF measurement at time t. Time-matched change from baseline to Day 1 in QTcF was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib on Day 1 are reported.
Time Frame	At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 of treatment Cycle 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline to Day 1 at 1 hour (h)	-1.6
Time-matched change from baseline to Day 1 at 2 h	-3.1
Time-matched change from baseline to Day 1 at 3 h	-2.6
Time-matched change from baseline to Day 1 at 4 h	-2.6
Time-matched change from baseline to Day 1 at 5 h	-1.4
Time-matched change from baseline to Day 1 at 6 h	-2.0
Time-matched change from baseline to Day 1 at 7 h	-1.5
Time-matched change from baseline to Day 1 at 10 h	-3.6
Time-matched change from baseline to Day 1 at 12 h	-2.2

10. Secondary Outcome

Title	Time-matched Change From Baseline in QTcF Interval (QT Interval Corrected by the Fridericia Formula) at the Time of Each Participant's Maximum Plasma Concentration of Nintedanib (BIBF 1120), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QTcF measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QTcF' at the time of the participant's maximum nintedanib plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline in QTcF interval at maximum BIBF 1120 concentration on Day 1	-2.8
Time-matched change from baseline in QTcF interval at maximum BIBF 1120 concentration on Day 15	-3.2

11. Secondary Outcome

Title	Time-Matched Change From Baseline in QTcF Interval at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202 (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QTcF measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QTcF' at the time of the participant's maximum BIBF 1202 (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline in QTcF interval at maximum BIBF 1202 concentration on Day 1	-2.5
Time-matched change from baseline in QTcF interval at maximum BIBF 1202 concentration on Day 15	-1.1

12. Secondary Outcome

Title	Time-Matched Change From Baseline in QTcF Interval at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202-glucuronide (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	Baseline QTcF measurement at time t was defined as the QTcF measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QTcF at time t was defined as the QTcF measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QTcF measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QTcF' at the time of the participant's maximum BIBF 1202-glucuronide (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change in QTcF from baseline at maximum BIBF 1202-glucuronide concentration on Day 1	-2.4
Time-matched change in QTcF from baseline at maximum BIBF 1202-glucuronide concentration on Day 15	-1.5

13. Secondary Outcome

Title	Average Time-matched Changes From Baseline in QTcF Interval Over 1 h to 12 h After Dosing on Days 1 and 15 of Treatment Cycle 1
Description	Average time-matched in QTcF interval (QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula) changes over 1 to 12 hours was evaluated using a t-test for paired observation. The mean differences between post-treatment values (Days 1 and 15) and baseline (Day -1) along with two-sided 90% confidence limits are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.
Time Frame	At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Averaged time-matched changes from baseline in QTcF interval over 1 h to 12 h after dosing on Day 1	-2.2
Averaged time-matched changes from baseline in QTcF interval over 1 h to 12 h after dosing on Day 15	0.5

14. Secondary Outcome

Title	Time-matched Changes From Baseline to Day 15 in QT Interval at 0 Hour (h), at 1 h, at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)
Description	QT interval is the electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 15 in QT at time t was defined as the QT measurement following administration of nintedanib on Day 15 obtained at time t minus baseline QT measurement at time t. 0 h is 5 min prior to dosing on Day 15. Time-matched change from baseline to Day 15 in QT was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib on Day 15 of Cycle 1are reported.
Time Frame	At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched QT interval change from baseline to Day 15 at -5 minutes (min)	1.0
Time-matched QT interval change from baseline to Day 15 at 1 hour (h)	0.5
Time-matched QT interval change from baseline to Day 15 at 2 h	1.6
Time-matched QT interval change from baseline to Day 15 at 3 h	4.4
Time-matched QT interval change from baseline to Day 15 at 4 h	4.7
Time-matched QT interval change from baseline to Day 15 at 5 h	5.1
Time-matched QT interval change from baseline to Day 15 at 6 h	7.7
Time-matched QT interval change from baseline to Day 15 at 7 h	7.1
Time-matched QT interval change from baseline to Day 15 at 10 h	3.4
Time-matched QT interval change from baseline to Day 15 at 12 h	4.2

15. Secondary Outcome

Title	Time-matched Changes From Baseline to Day 1 in QT Interval at 1 Hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)
Description	QT interval is the electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 in QT at time t was defined as the QT measurement following administration of nintedanib on Day 1 obtained at time t minus baseline QT measurement at time t. Time-matched change from baseline to Day 1 in QT was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib on Day 1 are reported.
Time Frame	At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched QT interval change from baseline to Day 1 at 1 hour (h)	-2.0
Time-matched QT interval change from baseline to Day 1 at 2 h	1.6
Time-matched QT interval change from baseline to Day 1 at 3 h	3.5
Time-matched QT interval change from baseline to Day 1 at 4 h	1.4
Time-matched QT interval change from baseline to Day 1 at 5 h	1.4
Time-matched QT interval change from baseline to Day 1 at 6 h	1.8
Time-matched QT interval change from baseline to Day 1 at 7 h	0.7
Time-matched QT interval change from baseline to Day 1 at 10 h	-1.7
Time-matched QT interval change from baseline to Day 1 at 12 h	-2.2

16. Secondary Outcome

Title	Time-Matched Change From Baseline in QT Interval at the Time of Each Patient's Maximum Plasma Concentration of Nintedanib (BIBF 1120), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QT interval is the (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QT at time t was defined as the QT measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QT measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QT' at the time of the participant's maximum nintedanib plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline in QT interval at maximum BIBF 1120 concentration on Day 1	0.9
Time-matched change from baseline in QT interval at maximum BIBF 1120 concentration on Day 15	-0.4

17. Secondary Outcome

Title	Time-Matched Change From Baseline in QT Interval at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202 (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QT interval is the (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QT at time t was defined as the QT measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QT measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QT' at the time of the participant's maximum BIBF 1202 (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline in QT interval at maximum BIBF 1202 concentration on Day 1	1.2
Time-matched change from baseline in QT interval at maximum BIBF 1202 concentration on Day 15	1.8

18. Secondary Outcome

Title	Time-Matched Change From Baseline in QT Interval at the Time of Each Patient's Maximum Plasma Concentration BIBF 1202-glucuronide (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QT interval is the (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave. Baseline QT measurement at time t was defined as the QT measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in QT at time t was defined as the QT measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline QT measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in QT' at the time of the participant's maximum BIBF 1202-glucuronide (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline in QT at maximum BIBF 1202-glucuronide concentration on Day 1	-0.4
Time-matched change from baseline in QT at maximum BIBF 1202-glucuronide concentration on Day 15	1.3

19. Secondary Outcome

Title	Averaged Time-matched Changes From Baseline in QT Interval (Electrocardiogram (ECG) Interval From the Beginning of the QRS Complex to the End of the T Wave) Over 1 h to 12 h After Dosing on Days 1 and 15 of Treatment Cycle 1
Description	Averaged time-matched QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) changes from baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120) to Day 1 (first drug dose nintedanib (BIBF 1120)) and to Day 15 (steady state) over 1 to 12 hours was evaluated using a t-test for paired observation. The mean differences between post-treatment values (Days 1 and 15) and baseline (Day -1) along with two-sided 90% confidence limits are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.
Time Frame	At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Averaged time-matched changes from baseline in QT interval over 1 h to 12 h after dosing on Day 1	0.9
Averaged time-matched changes from baseline in QT interval over 1 h to 12 h after dosing on Day 15	4.2

20. Secondary Outcome

Title	Time-Matched Heart Rate (HR) Changes From Baseline to Day 15 at 0 Hour (h), at 1 h, at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)
Description	Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib (BIBF 1120) at time t. Time-matched change from baseline to Day 15 in HR at time t was defined as the HR measurement following administration of nintedanib (BIBF 1120) on Day 15 obtained at time t minus baseline HR measurement at time t. 0 h is 5 min prior to dosing on Day 15. Time-matched change from baseline to Day 15 in HR was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib (BIBF 1120) on Day 15 of Cycle 1 are reported.
Time Frame	At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched heart rate (HR) change from baseline to Day 15 at -5 minutes (min)	0.9
Time-matched heart rate (HR) change from baseline to Day 15 at 1 h	-0.3
Time-matched heart rate (HR) change from baseline to Day 15 at 2 h	-2.0
Time-matched heart rate (HR) change from baseline to Day 15 at 3 h	-3.3
Time-matched heart rate (HR) change from baseline to Day 15 at 4 h	-3.4
Time-matched heart rate (HR) change from baseline to Day 15 at 5 h	-3.1
Time-matched heart rate (HR) change from baseline to Day 15 at 6 h	-3.8
Time-matched heart rate (HR) change from baseline to Day 15 at 7 h	-2.8
Time-matched heart rate (HR) change from baseline to Day 15 at 10 h	-2.4
Time-matched heart rate (HR) change from baseline to Day 15 at 12 h	-1.6

21. Secondary Outcome

Title	Time-Matched Heart Rate (HR) Changes From Baseline to Day 1 at 1 Hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)
Description	Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib (BIBF 1120) at time t. Time-matched change from baseline to Day 1 in HR at time t was defined as the HR measurement following administration of nintedanib (BIBF 1120) on Day 1 obtained at time t minus baseline HR measurement at time t. Time-matched change from baseline to Day 1 in HR was modelled using a linear mixed-effects model for repeated measures which included 'time' as repeated measures and the time-matched baseline value as a covariate. Adjusted means with corresponding 2-sided 90% confidence intervals at 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h and 12 h after dosing of nintedanib (BIBF 1120) on Day 1 are reported.
Time Frame	At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched heart rate (HR) change from baseline to Day 1 at 1 hour (h)	-0.0
Time-matched heart rate (HR) change from baseline to Day 1 at 2 h	-2.9
Time-matched heart rate (HR) change from baseline to Day 1 at 3 h	-3.8
Time-matched heart rate (HR) change from baseline to Day 1 at 4 h	-2.5
Time-matched heart rate (HR) change from baseline to Day 1 at 5 h	-1.8
Time-matched heart rate (HR) change from baseline to Day 1 at 6 h	-2.2
Time-matched heart rate (HR) change from baseline to Day 1 at 7 h	-1.4
Time-matched heart rate (HR) change from baseline to Day 1 at 10 h	-1.3
Time-matched heart rate (HR) change from baseline to Day 1 at 12 h	0.0

22. Secondary Outcome

Title	Time-Matched Change From Baseline in Heart Rate (HR) at the Time of Each Patient's Maximum Nintedanib (BIBF 1120) Plasma Concentration, Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in HR at time t was defined as the HR measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline HR measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in HR' at the time of the participant's maximum nintedanib plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline in HR at maximum BIBF 1120 concentration on Day 1	-2.0
Time-matched change from baseline in HR at maximum BIBF 1120 concentration on Day 15	-2.1

23. Secondary Outcome

Title	Time-Matched Change From Baseline in Heart Rate (HR) at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202 (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in HR at time t was defined as the HR measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline HR measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in HR' at the time of the participant's maximum BIBF 1202 (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline in HR at maximum BIBF 1202 concentration on Day 1	-2.3
Time-matched change from baseline in HR at maximum BIBF 1202 concentration on Day 15	-2.0

24. Secondary Outcome

Title	Time-Matched Change From Baseline in Heart Rate (HR) at the Time of Each Patient's Maximum Plasma Concentration of BIBF 1202-glucuronide (a Nintedanib (BIBF 1120) Metabolite), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	Baseline heart rate (HR) measurement at time t was defined as the HR measurement collected 1 day prior to the day of the first administration of nintedanib at time t. Time-matched change from baseline to Day 1 (Day 15) in HR at time t was defined as the HR measurement following administration of nintedanib on Day 1 (Day 15) obtained at time t minus baseline HR measurement at time t. For each participant 'Time-matched change from baseline to Day 1 (Day 15) in HR' at the time of the participant's maximum BIBF 1202-glucuronide (a nintedanib (BIBF 1120) metabolite) plasma concentration was obtained and the mean across all participants calculated. Corresponding two-sided 90% confidence intervals based on the t-distribution are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of treatment cycle 1. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Time-matched change from baseline in HR at maximum BIBF 1202-glucuronide concentration on Day 1	-1.2
Time-matched change from baseline in HR at maximum BIBF 1202-glucuronide concentration on Day 15	-1.6

25. Secondary Outcome

Title	Averaged Time-Matched Heart Rate (HR) Change From Baseline Over 1 to 12 Hours, Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	Averaged time-matched heart rate changes from baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) to Day 1 (first drug dose nintedanib (BIBF 1120)) and to Day 15 (steady state) over 1 to 12 hours was evaluated using a t-test for paired observation. The mean differences between post-treatment values (Days 1 and 15) and baseline (Day -1) along with two-sided 90% confidence limits are reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 1 and on Day 15.
Time Frame	At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Averaged time-matched HR change from baseline over 1 to 12 hours on Day 1	-1.9
Averaged time-matched HR change from baseline over 1 to 12 hours on Day 15	-2.5

26. Secondary Outcome

Title	Frequency of Patients With Maximum Time-Matched QTcF Interval Change From Baseline Categorized by Magnitude of Change, Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of patients with maximum time-matched change from baseline in the QTcF interval observed at each point in time, i.e., 9 time points on Day 1 and 10 timepoints on Day 15 is reported. 3 categories of individual QTcF increases from baseline to maximum value were defined: <= 30 milliseconds (ms) > 30 to 60 milliseconds (ms) > 60 milliseconds (ms) Changes more than 60 ms in the QTcF interval represent notable changes. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
<= 30 milliseconds (ms)	64 100%
> 30 to 60 milliseconds (ms)	0 0%
> 60 milliseconds (ms)	0 0%
<= 30 milliseconds (ms)	57 89.1%
> 30 to 60 milliseconds (ms)	6 9.4%
> 60 milliseconds (ms)	0 0%

27. Secondary Outcome

Title	Frequency of Patients With Maximum Time-Matched QT Interval (Electrocardiogram (ECG) Interval From the Beginning of the QRS Complex to the End of the T Wave) Change From Baseline Categorized by Magnitude of Change, Days 1 and 15
Description	Number of patients with maximum time-matched change from baseline in the QT interval observed at each point in time, i.e., 9 time points on Day 1 and 10 timepoints on Day 15 is reported. 3 categories of individual QTcF increases from baseline to maximum value were defined: <= 30 milliseconds (ms) > 30 to 60 milliseconds (ms) > 60 milliseconds (ms) Changes more than 60 ms in the QT interval represent notable changes. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
<= 60 milliseconds (ms)	64 100%
> 60 milliseconds (ms)	0 0%
<= 60 milliseconds (ms)	62 96.9%
> 60 milliseconds (ms)	1 1.6%

28. Secondary Outcome

Title	Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF ≤450 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of participants with new onset (not present at any time pre-dose) of QTcF ≤450 milliseconds (ms) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Number of participants with new onset of QTcF ≤450 (ms) on Day 1	3 4.7%
Number of participants with new onset of QTcF ≤450 (ms) on Day 15	2 3.1%

29. Secondary Outcome

Title	Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF >450 to 470 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of participants with new onset of QTcF >450 to 470 milliseconds (ms) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of the first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Number of participants with new onset of QTcF >450 to 470 ms on Day 1	1 1.6%
Number of participants with new onset of QTcF >450 to 470 ms on Day 15	1 1.6%

30. Secondary Outcome

Title	Number of Participants With New Onset of QTcF> 470 to 500 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of participants with new onset of QTcF> 470 to 500 milliseconds (ms) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Number of participants with new onset of QTcF> 470 to 500 ms on Day 1	0 0%
Number of participants with new onset of QTcF> 470 to 500 ms on Day 15	1 1.6%

31. Secondary Outcome

Title	Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF> 500 Milliseconds (ms) (Notable Prolongation), Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	QTcF interval is the QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected for the effects of heart rate (HR) by the Fridericia formula. Number of participants with new onset of QTcF> 500 milliseconds (ms) (notable prolongation) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Number of participants with new onset of QTcF> 500 (ms) on Day 1, 1-12 hour (h)	0 0%
Number of participants with new onset of QTcF> 500 (ms) (notable prolongation) on Day 15, -0:05-12 h	0 0%

32. Secondary Outcome

Title	Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QT (Electrocardiogram (ECG) Interval From the Beginning of the QRS Complex to the End of the T Wave) > 500 ms (Notable Prolongation), Days 1 and 15 of Treatment Cycle 1
Description	Number of participants with new onset of QT (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave)> 500 milliseconds (ms) (notable prolongation) on Day 1 (first drug dose nintedanib (BIBF 1120)) and Day 15 (steady state) compared to the baseline (Day -1 prior to the first dosing of nintedanib (BIBF 1120)) is reported. Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Number of participants with new onset of QT> 500 (ms) on Day 1, 1-12 hour (h)	0 0%
Number of participants with new onset of QT> 500 (ms) on Day 15, -0:05-12 h	0 0%

33. Secondary Outcome

Title	Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval
Description	The PR interval is an electrocardiogram (ECG) interval and is the time from the onset of the P wave to the start of the QRS complex (combination of the Q wave, R wave and S wave). It reflects conduction through the atrioventricular node (AV) node. The normal PR interval is between 120 - 200 milliseconds (ms) (0.12-0.20s) in duration. Absolute values at baseline (Day-1 prior to the first dosing of nintedanib) and at Day 1 (first drug dose of nintedanib (BIBF 1120)) and changes from baseline to Day 1 at each point in time i.e., 10 time points from 0 to 12 in the PR interval are reported.
Time Frame	At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Absolute value in PR interval on Day -1 at -5 minutes (min)	164.7 (23.8)
Absolute value in PR interval on Day -1 at 1 hour (h)	165.7 (24.9)
Absolute value in PR interval on Day -1 at 2 h	166.8 (24.9)
Absolute value in PR interval on Day -1 at 3 h	166.6 (24.0)
Absolute value in PR interval on Day -1 at 4 h	168.1 (26.9)
Absolute value in PR interval on Day -1 at 5 h	167.2 (26.3)
Absolute value in PR interval on Day -1 at 6 h	168.1 (26.4)
Absolute value in PR interval on Day -1 at 7 h	168.9 (27.5)
Absolute value in PR interval on Day -1 at 10 h	168.0 (26.7)
Absolute value in PR interval on Day -1 at 12 h	170.0 (29.4)
Absolute value in PR interval on Day 1 at -5 min	165.7 (25.6)
Absolute value in PR interval on Day 1 at 1 h	167.4 (28.2)
Absolute value in PR interval on Day 1 at 2 h	169.4 (28.2)
Absolute value in PR interval on Day 1 at 3 h	170.0 (27.3)
Absolute value in PR interval on Day 1 at 4 h	170.0 (28.2)
Absolute value in PR interval on Day 1 at 5 h	169.4 (27.5)
Absolute value in PR interval on Day 1 at 6 h	170.8 (27.9)
Absolute value in PR interval on Day 1 at 7 h	169.9 (27.0)
Absolute value n PR interval on Day 1 at 10 h	169.8 (26.3)
Absolute value in PR interval on Day 1 at 12 h	171.3 (28.7)
Time-matched change from Day -1 to Day 1 in PR interval at -5 min	0.7 (7.6)
Time-matched change from Day -1 to Day 1 in PR interval at 1 h	1.7 (11.6)
Time-matched change from Day -1 to Day 1 in PR interval at 2 h	2.6 (10.3)
Time-matched change from Day -1 to Day 1 in PR interval at 3 h	3.4 (9.1)
Time-matched change from Day -1 to Day 1 in PR interval at 4 h	2.2 (9.1)
Time-matched change from Day -1 to Day 1 in PR interval at 5 h	2.8 (10.7)
Time-matched change from Day -1 to Day 1 in PR interval at 6 h	3.3 (9.8)
Time-matched change from Day -1 to Day 1 in PR interval at 7 h	1.6 (9.3)
Time-matched change from Day -1 to Day 1 in PR interval at 10 h	1.8 (8.6)
Time-matched change from Day -1 to Day 1 in PR interval at 12 h	0.7 (9.4)

34. Secondary Outcome

Title	Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval
Description	The PR interval is an electrocardiogram (ECG) interval and is the time from the onset of the P wave to the start of the QRS complex (combination of the Q wave, R wave and S wave). It reflects conduction through the atrioventricular node (AV) node. The normal PR interval is between 120 - 200 milliseconds (ms) (0.12-0.20s) in duration. Absolute values at baseline (Day-1 prior to the first dosing of nintedanib (BIBF 1120) and at Day 15 (steady state) and changes from baseline to Day 15 at each point in time i.e., 10 time points from 0 to 12 in the PR interval are reported.
Time Frame	At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Absolute value in PR interval on Day -1 at -5 minutes (min)	164.7 (24.0)
Absolute value in PR interval on Day -1 at 1 h	165.7 (25.1)
Absolute value in PR interval on Day -1 at 2 h	166.8 (25.1)
Absolute value in PR interval on Day -1 at 3 h	166.5 (24.2)
Absolute value in PR interval on Day -1 at 4 h	168.0 (27.2)
Absolute value in PR interval on Day -1 at 5 h	167.2 (26.5)
Absolute value in PR interval on Day -1 at 6 h	168.3 (26.6)
Absolute value in PR interval on Day -1 at 7 h	168.9 (27.7)
Absolute value in PR interval on Day -1 at 10 h	168.1 (26.9)
Absolute value in PR interval on Day -1 at 12 h	170.1 (29.7)
Absolute value in PR interval on Day 15 at -5 min	164.5 (24.4)
Absolute value in PR interval on Day 15 at 1 h	166.1 (25.3)
Absolute value in PR interval on Day 15 at 2 h	166.8 (26.2)
Absolute value in PR interval on Day 15 at 3 h	167.4 (25.3)
Absolute value in PR interval on Day 15 at 4 h	168.7 (27.4)
Absolute value in PR interval on Day 15 at 5 h	167.7 (27.8)
Absolute value in PR interval on Day 15at 6 h	169.3 (26.7)
Absolute value in PR interval on Day 15 at 7 h	169.0 (27.9)
Absolute value in PR interval on Day 15 at 10 h	169.1 (27.9)
Absolute value in PR interval on Day 15 at 12:00 h:min	168.8 (27.9)
Time-matched change from Day -1 to Day 15 in PR interval at -5 min	-0.1 (10.6)
Time-matched change from Day -1 to Day 15 in PR interval at 1 h	0.5 (12.5)
Time-matched change from Day -1 to Day 15 in PR interval at 2 h	-0.0 (12.7)
Time-matched change from Day -1 to Day 15 in PR interval at 3 h	0.9 (14.6)
Time matched - change from Day -1 to Day 15 in PR interval at 4 h	0.9 (12.2)
Time-matched change from Day -1 to Day 15 in PR interval at 5 h	0.9 (13.7)
Time-matched change from Day -1 to Day 15 in PR interval at 6 h	1.3 (11.8)
Time-matched change from Day -1 to Day 15 in PR interval at 7 h	0.6 (13.2)
Time-matched change from Day -1 to Day 15 in PR interval at 10 h	1.2 (11.2)
Time-matched change from Day -1 to Day 15 in PR interval at 12 h	-1.5 (12.5)

35. Secondary Outcome

Title	Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval
Description	QRS interval is an electrocardiogram (ECG) interval and is the time interval from the onset to the end of the QRS complex (combination of the Q wave, R wave and S wave). The normal QRS duration is less than 120 milliseconds (ms). Absolute values and changes from baseline (Day-1 prior to the first dosing of nintedanib) to Day 1 (first drug dose of nintedanib (BIBF 1120)) at each point in time i.e., 10 time points from 0 to 12 in the QRS interval are reported.
Time Frame	At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Absolute value in QRS interval on Day -1 at -5 minutes (min)	92.4 (11.8)
Absolute value in QRS interval on Day -1 at 1 h	93.7 (11.0)
Absolute value in QRS interval on Day -1 at 2 h	93.2 (10.5)
Absolute value in QRS interval on Day -1 at 3 h	93.6 (10.8)
Absolute value in QRS interval on Day -1 at 4 h	92.7 (9.8)
Absolute value in QRS interval on Day -1 at 5 h	92.6 (11.0)
Absolute value in QRS interval on Day -1 at 6 h	92.5 (10.3)
Absolute value in QRS interval on Day -1 at 7 h	93.0 (10.6)
Absolute value in QRS interval on Day -1 at 10 h	92.8 (11.7)
Absolute value in QRS interval on Day -1, 12 h	92.5 (10.4)
Absolute value in QRS interval on Day 1 at -5 min	92.6 (10.1)
Absolute value in QRS interval on Day 1 at 1 h	93.2 (11.0)
Absolute value in QRS interval on Day 1 at 2 h	93.0 (10.4)
Absolute value in QRS interval on Day 1 at 3 h	93.3 (10.3)
Absolute value in QRS interval on Day 1 at 4 h	93.5 (11.1)
Absolute value in QRS interval on Day 1 at 5 h	93.4 (11.5)
Absolute value in QRS interval on Day 1 at 6 h	93.4 (10.7)
Absolute value in QRS interval on Day 1 at 7 h	93.2 (11.3)
Absolute value in QRS interval on Day 1 at 10 h	92.3 (10.6)
Absolute value in QRS interval on Day 1 at 12 h	92.8 (10.9)
Time-matched change from Day -1 to Day 1 in QRS interval at -5 min	0.7 (5.1)
Time-matched change from Day -1 to Day 1 in QRS interval at 1 h	-0.5 (5.2)
Time-matched change from Day -1 to Day 1 in QRS interval 2 h	-0.2 (4.4)
Time-matched change from Day -1 to Day 1 in QRS interval at 3h	-0.3 (4.4)
Time-matched change from Day -1 to day 1 in QRS interval at 4 h	0.2 (4.7)
Time-matched change from Day -1 to Day 1 in QRS interval at 5 h	0.2 (5.4)
Time-matched change from Day -1 to Day 1 in QRS interval at 6 h	0.3 (5.6)
Time-matched change from Day -1 to Day 1 in QRS interval at 7 h	-0.2 (4.7)
Time-matched change from Day -1 to Day 1 in QRS interval at 10 h	-0.5 (4.9)
Time-matched change from Day -1 to Day 1 in QRS interval at 12 h	0.3 (4.9)

36. Secondary Outcome

Title	Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval
Description	QRS interval is an electrocardiogram (ECG) interval and is the time interval from the onset to the end of the QRS complex (combination of the Q wave, R wave and S wave). The normal QRS duration is less than 120 milliseconds (ms). Absolute values and changes from baseline (Day-1 prior to the first dosing of nintedanib) to Day 15 (steady state) at each point in time i.e., 10 time points from 0 to 12 in the QRS interval are reported.
Time Frame	At 5 minutes (min) before the first dose and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 15. Baseline (Day -1) values were taken at exactly the same time points as on Day 15.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Absolute value in QRS interval on Day -1 at -5 minutes (min)	92.5 (11.8)
Absolute value in QRS interval on Day -1 at 1 hour (h)	93.8 (11.1)
Absolute value in QRS interval on Day -1 at 2 h	93.3 (10.6)
Absolute value in QRS interval on Day -1 at 3 h	93.6 (10.9)
Absolute value in QRS interval on Day -1 at 4 h	92.7 (9.9)
Absolute value in QRS interval on Day -1 at 5 h	92.7 (11.0)
Absolute value in QRS interval on Day -1 at 6 h	92.7 (10.3)
Absolute value in QRS interval on Day -1 at 7 h	93.1 (10.6)
Absolute value in QRS interval on Day -1 at 10 h	92.8 (11.8)
Absolute value in QRS interval on Day -1 at 12 h	92.6 (10.4)
Absolute value in QRS interval on Day 15 at -5 min	93.3 (11.0)
Absolute value Day 15, 1 h	93.9 (10.3)
Absolute value in QRS interval on Day 15 at 2 h	93.0 (11.5)
Absolute value in QRS interval on Day 15 at 3 h	92.9 (11.1)
Absolute value in QRS interval on Day 15 at 4 h	92.6 (11.2)
Absolute value in QRS interval on Day 15 at 5 h	93.6 (10.9)
Absolute value in QRS interval on Day 15 at 6 h	93.1 (11.1)
Absolute value in QRS interval on Day 15 at 7 h	93.1 (11.3)
Absolute value in QRS interval on Day 15 at 10 h	92.8 (10.7)
Absolute value in QRS interval on Day 15 at 12 h	93.7 (11.5)
Time-matched change from Day -1 to Day 15 in QRS interval at -5 min	0.8 (5.4)
Time-matched change from Day -1 to Day 15 in QRS interval at 1 h	0.0 (5.1)
Time-matched change from Day -1 to Day 15 in QRS interval at 2 h	-0.3 (5.3)
Time-matched change from Day -1 to Day 15 in QRS interval at 3 h	-0.8 (5.7)
Time-matched change from Day -1 to Day 15 in QRS interval at 4 h	-0.6 (5.4)
Time-matched change from Day -1 to Day 15 in QRS interval at 5 h	0.5 (7.3)
Time-matched change from Day -1 to Day 15 in QRS interval at 6 h	-0.1 (5.3)
Time-matched change from Day -1 to Day 15 in QRS interval at 7 h	-0.4 (5.3)
Time-matched change from Day -1 to Day 15 in QRS interval at 10 h	0.1 (5.1)
Time-matched change from Day -1 to Day 15 in QRS interval at 12 h	1.0 (4.7)

37. Secondary Outcome

Title	Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1
Description	Based on the interpretation of the electrocardiogram (ECG) patients were classified in 3 categories: Normal (a normal ECG reading would be a reading that includes the following normal findings: 1) normal general features; 2) no arrhythmia; 3) no conduction delays; 4) T-wave morphology of normal; and 5) normal U-wave morphology) on Day 1 or on Day 15) Not normal and not normal at baseline (an abnormal ECG reading would be a reading that includes one or more of the following abnormal findings: 1) abnormal general features; 2) arrhythmia; 3) conduction delays; 4) T-wave morphology of flat, inverted or biphasic; and 5) abnormal U-wave morphology) on Day 1 or on Day 15) Not normal and new onset of finding; Time frame: Baseline (Day -1) values were taken at exactly the same time points as on Day 15.
Time Frame	At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.

Outcome Measure Data

Analysis Population Description

Full analysis set electrocardiogram (FAS-ECG): All patients in the treated set who were treated with nintedanib (BIBF 1120) and had at least 1 time-matched pair of QT interval (electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) measurements available from baseline and from either Day 1 or Day 15 of Treatment Cycle 1 (first 4-week cycle). Only participants with non-missing outcomes were included in the analysis.

Arm/Group Title	Nintedanib (BIBF 1120)
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.
Measure Participants	64
Normal	39 60.9%
Not normal and not normal at baseline	24 37.5%
Not normal and new onset of finding	1 1.6%
Normal	37 57.8%
Not normal and not normal at baseline	25 39.1%
Not normal and new onset of finding	1 1.6%

38. Secondary Outcome

Title	Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0
Description	The number of participants who experienced adverse events graded according to NCI CTCAE version 3.0, is reported below.The maximum grade of adverse event intensity for each type of treatment-related adverse event was recorded for each patient. Grade 1 - Mild AE Grade 2 - Moderate AE Grade 3 - Severe AE Grade 4 - Life-threatening or disabling AE Grade 5 - Death related to AE
Time Frame	From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.

Outcome Measure Data

Analysis Population Description

Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Grade 1	11 17.2%	5 15.6%
Grade 2	16 25%	6 18.8%
Grade 3	14 21.9%	16 50%
Grade 4	10 15.6%	2 6.3%
Grade 5	7 10.9%	1 3.1%

39. Secondary Outcome

Title	Number of Participants With Adverse Events Leading to Dose Reduction
Description	Number of participants who experienced Adverse Events which led to dose reduction of the trial medication is reported for each treatment arm.
Time Frame	From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.

Outcome Measure Data

Analysis Population Description

Treated Set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Count of Participants [Participants]	16 25%	8 25%

40. Secondary Outcome

Title	Number of Participants With Adverse Events Leading to Discontinuation of Trial Drug
Description	Number of participants with Adverse Events which lead to discontinuation of trial medication drug is reported for each treatment arm.
Time Frame	From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.

Outcome Measure Data

Analysis Population Description

Treated Set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Count of Participants [Participants]	11 17.2%	5 15.6%

41. Secondary Outcome

Title	Number of Participants With Adverse Events Requiring or Prolonging Hospitalisation
Description	Number of participants who experienced Adverse Events which required or prolonged hospitalisation of patients is reported for each treatment arm.
Time Frame	From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.

Outcome Measure Data

Analysis Population Description

Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	32
Count of Participants [Participants]	15 23.4%	10 31.3%

42. Secondary Outcome

Title	Duration of Hospital Stays Due to Adverse Events Requiring or Prolonging Hospitalisation
Description	Duration of hospitalisation in days for each treatment arm is reported for those patients who experienced adverse events which required or prolonged hospitalisation (of the patients).
Time Frame	From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.

Outcome Measure Data

Analysis Population Description

All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment and experienced Adverse Events requiring or prolonging hospitalisation.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	15	10
Mean (Standard Deviation) [days]	11.40 (8.56)	13.10 (8.32)

43. Secondary Outcome

Title	Frequency of Patients With Possible Clinically Significant Abnormal Lab Values
Description	Number of patients with possible clinically significant abnormal lab values for the lab parameters alkaline phosphatase, activated partial thromboplastin time (APTT), creatinine, haemoglobin, prothrombin time (PT)-international normalized ratio (INR), potassium, lymphocytes, sodium, neutrophils, platelets, aspartate amino transferase (AST), alanine aminotransferase (ALT), bilirubin and white blood cell count is reported. Only lab values with CTCAE rule for possible clinical significance are displayed.
Time Frame	From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.

Outcome Measure Data

Analysis Population Description

Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment. 1 patient in the Sunitinib arm did not have on-treatment lab values.

Arm/Group Title	Nintedanib (BIBF 1120)	Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.	Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
Measure Participants	64	31
Alkaline phosphatase	2 3.1%	3 9.4%
APTT (Activated partial thrombopl. time)	7 10.9%	0 0%
Creatinine	4 6.3%	5 15.6%
Haemoglobin	6 9.4%	6 18.8%
Prothrombin time (PT)-international normalized ratio (INR)	5 7.8%	0 0%
Potassium	14 21.9%	4 12.5%
Lymphocytes	8 12.5%	11 34.4%
Sodium	14 21.9%	3 9.4%
Neutrophils	3 4.7%	9 28.1%
Platelets	2 3.1%	3 9.4%
Aspartate amino Transferase (AST)	10 15.6%	1 3.1%
Alanine aminotransferase (ALT)	14 21.9%	3 9.4%
Bilirubin, total	4 6.3%	3 9.4%
White blood cell count	0 0%	7 21.9%

Adverse Events

Time Frame	From first dose of study drug administration up to 28 days after last dose of study drug, up to 121 months.
Adverse Event Reporting Description	Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
Arm/Group Title	Nintedanib (BIBF 1120)		Sunitinib
Arm/Group Description	Participants received orally (swallowed) soft gelatine capsules of nintedanib (BIBF 1120) twice daily (bid) starting with a dose of 200 milligram (mg) bid given continuously in 4-week cycles. Nintedanib was to be swallowed unchewed with about 200 milliliter (mL) of water after food intake with a dosing interval of approximately 12 hours. In case of Adverse Events, the dose was to be reduced to 150 mg bid and 100 mg bid, respectively. The dose was continued daily until withdrawal criteria were fulfilled.		Participants received orally (swallowed) hard capsule of sunitinib starting with a dose of 50 milligram (mg) once daily (qd). In case of Adverse Events the dose was to be reduced to 37.5 mg once daily and 25 mg once daily, respectively. The daily dosing was performed in 6-week cycles (4 weeks on and 2 weeks off) until withdrawal criteria were fulfilled.
All Cause Mortality
	Nintedanib (BIBF 1120)		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/64 (78.1%)		25/32 (78.1%)
Serious Adverse Events
	Nintedanib (BIBF 1120)		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/64 (31.3%)		11/32 (34.4%)
Cardiac disorders
Myocardial infarction	1/64 (1.6%)		1/32 (3.1%)
Gastrointestinal disorders
Abdominal pain	0/64 (0%)		2/32 (6.3%)
Abdominal pain upper	0/64 (0%)		1/32 (3.1%)
Ascites	0/64 (0%)		1/32 (3.1%)
Colitis	1/64 (1.6%)		0/32 (0%)
Diarrhoea	0/64 (0%)		1/32 (3.1%)
Gastrointestinal haemorrhage	0/64 (0%)		1/32 (3.1%)
Gastrooesophageal reflux disease	1/64 (1.6%)		0/32 (0%)
Large intestinal haemorrhage	1/64 (1.6%)		0/32 (0%)
Nausea	0/64 (0%)		3/32 (9.4%)
Vomiting	0/64 (0%)		1/32 (3.1%)
Oesophagitis	0/64 (0%)		1/32 (3.1%)
General disorders
Asthenia	1/64 (1.6%)		0/32 (0%)
Disease progression	0/64 (0%)		1/32 (3.1%)
Hernia	0/64 (0%)		1/32 (3.1%)
Obstruction	0/64 (0%)		1/32 (3.1%)
Pyrexia	0/64 (0%)		1/32 (3.1%)
Hepatobiliary disorders
Jaundice	1/64 (1.6%)		0/32 (0%)
Cholecystitis acute	1/64 (1.6%)		0/32 (0%)
Cholecystitis chronic	1/64 (1.6%)		0/32 (0%)
Cholelithiasis	1/64 (1.6%)		0/32 (0%)
Infections and infestations
Cellulitis	1/64 (1.6%)		0/32 (0%)
Injury, poisoning and procedural complications
Incisional hernia, obstructive	0/64 (0%)		1/32 (3.1%)
Poisoning	0/64 (0%)		1/32 (3.1%)
Investigations
Blood pressure increased	1/64 (1.6%)		0/32 (0%)
Metabolism and nutrition disorders
Dehydration	0/64 (0%)		1/32 (3.1%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/64 (1.6%)		0/32 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	1/64 (1.6%)		0/32 (0%)
Metastases to spine	1/64 (1.6%)		0/32 (0%)
Bladder transitional cell carcinoma	1/64 (1.6%)		0/32 (0%)
Malignant neoplasm progression	7/64 (10.9%)		0/32 (0%)
Nervous system disorders
Cerebrovascular accident	1/64 (1.6%)		0/32 (0%)
Epilepsy	1/64 (1.6%)		0/32 (0%)
Quadriparesis	1/64 (1.6%)		0/32 (0%)
Psychiatric disorders
Confusional state	1/64 (1.6%)		0/32 (0%)
Renal and urinary disorders
Urinary bladder haemorrhage	1/64 (1.6%)		0/32 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/64 (1.6%)		1/32 (3.1%)
Pleurisy	1/64 (1.6%)		1/32 (3.1%)
Pulmonary embolism	1/64 (1.6%)		0/32 (0%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/64 (0%)		1/32 (3.1%)
Surgical and medical procedures
Hernia repair	0/64 (0%)		1/32 (3.1%)
Vascular disorders
Thrombophlebitis	1/64 (1.6%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Nintedanib (BIBF 1120)		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/64 (85.9%)		27/32 (84.4%)
Blood and lymphatic system disorders
Anaemia	4/64 (6.3%)		5/32 (15.6%)
Neutropenia	0/64 (0%)		3/32 (9.4%)
Thrombocytopenia	0/64 (0%)		2/32 (6.3%)
Cardiac disorders
Aortic valve sclerosis	1/64 (1.6%)		2/32 (6.3%)
Tachycardia	1/64 (1.6%)		2/32 (6.3%)
Endocrine disorders
Hyperthyroidism	1/64 (1.6%)		2/32 (6.3%)
Hypothyroidism	2/64 (3.1%)		5/32 (15.6%)
Eye disorders
Periorbital oedema	0/64 (0%)		2/32 (6.3%)
Gastrointestinal disorders
Abdominal pain	5/64 (7.8%)		1/32 (3.1%)
Abdominal pain upper	5/64 (7.8%)		2/32 (6.3%)
Constipation	5/64 (7.8%)		4/32 (12.5%)
Diarrhoea	40/64 (62.5%)		15/32 (46.9%)
Dry mouth	5/64 (7.8%)		1/32 (3.1%)
Dyspepsia	3/64 (4.7%)		7/32 (21.9%)
Flatulence	4/64 (6.3%)		3/32 (9.4%)
Gastrooesophageal reflux disease	0/64 (0%)		3/32 (9.4%)
Haemorrhoidal haemorrhage	0/64 (0%)		2/32 (6.3%)
Nausea	25/64 (39.1%)		8/32 (25%)
Stomatitis	0/64 (0%)		10/32 (31.3%)
Vomiting	10/64 (15.6%)		6/32 (18.8%)
General disorders
Asthenia	5/64 (7.8%)		2/32 (6.3%)
Fatigue	17/64 (26.6%)		8/32 (25%)
Hyperthermia	2/64 (3.1%)		2/32 (6.3%)
Mucosal inflammation	0/64 (0%)		2/32 (6.3%)
Pain	4/64 (6.3%)		0/32 (0%)
Infections and infestations
Nasopharyngitis	2/64 (3.1%)		2/32 (6.3%)
Investigations
Alanine aminotransferase increased	5/64 (7.8%)		1/32 (3.1%)
Aspartate aminotransferase increased	6/64 (9.4%)		1/32 (3.1%)
Blood creatinine increased	3/64 (4.7%)		3/32 (9.4%)
Blood thyroid stimulating hormone increased	0/64 (0%)		2/32 (6.3%)
Gamma-glutamyltransferase increased	8/64 (12.5%)		1/32 (3.1%)
Lipase increased	2/64 (3.1%)		4/32 (12.5%)
Weight decreased	8/64 (12.5%)		2/32 (6.3%)
Weight increased	2/64 (3.1%)		3/32 (9.4%)
Amylase increased	1/64 (1.6%)		2/32 (6.3%)
Blood glucose increased	2/64 (3.1%)		2/32 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	12/64 (18.8%)		6/32 (18.8%)
Hyponatraemia	4/64 (6.3%)		0/32 (0%)
Musculoskeletal and connective tissue disorders
Back pain	4/64 (6.3%)		1/32 (3.1%)
Osteoarthritis	0/64 (0%)		2/32 (6.3%)
Nervous system disorders
Dysgeusia	3/64 (4.7%)		3/32 (9.4%)
Headache	7/64 (10.9%)		1/32 (3.1%)
Lethargy	3/64 (4.7%)		2/32 (6.3%)
Renal and urinary disorders
Haematuria	5/64 (7.8%)		0/32 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/64 (3.1%)		3/32 (9.4%)
Dyspnoea	1/64 (1.6%)		4/32 (12.5%)
Skin and subcutaneous tissue disorders
Blister	0/64 (0%)		2/32 (6.3%)
Palmar-plantar erythrodysaesthesia syndrome	0/64 (0%)		10/32 (31.3%)
Rash	1/64 (1.6%)		3/32 (9.4%)
Dry skin	0/64 (0%)		2/32 (6.3%)
Vascular disorders
Aortic arteriosclerosis	2/64 (3.1%)		2/32 (6.3%)
Hypertension	2/64 (3.1%)		5/32 (15.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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