Carcinoma, Renal Cell
Conditions
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).
Interventions
DRUGBIBF 1120
VEGF inhibitor
DRUGsunitinib
VEGF inhibitor
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
Countries
Hungary, Poland, Romania, Ukraine, United Kingdom
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Nintedanib (BIBF 1120) 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. | 64 |
| Sunitinib 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. | 32 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Not treated | 3 | 0 |
| Overall Study | Other than listed | 5 | 1 |
| Overall Study | Patient refusal to continue | 4 | 0 |
| Overall Study | Progressive disease | 47 | 25 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Sunitinib | Nintedanib (BIBF 1120) | Total |
|---|---|---|---|
| Age, Continuous | 55.5 Years STANDARD_DEVIATION 11.4 | 60.4 Years STANDARD_DEVIATION 9.7 | 58.8 Years STANDARD_DEVIATION 10.5 |
| QTcF interval baseline values 10 h | — | 406.6 millisecconds (ms) STANDARD_DEVIATION 19.2 | 406.6 millisecconds (ms) STANDARD_DEVIATION 19.2 |
| QTcF interval baseline values 12 h | — | 406.0 millisecconds (ms) STANDARD_DEVIATION 19.2 | 406.0 millisecconds (ms) STANDARD_DEVIATION 19.2 |
| QTcF interval baseline values 1 hour (h) | — | 406.0 millisecconds (ms) STANDARD_DEVIATION 20.3 | 406.0 millisecconds (ms) STANDARD_DEVIATION 20.3 |
| QTcF interval baseline values 2 h | — | 405.3 millisecconds (ms) STANDARD_DEVIATION 19.4 | 405.3 millisecconds (ms) STANDARD_DEVIATION 19.4 |
| QTcF interval baseline values 3 h | — | 406.7 millisecconds (ms) STANDARD_DEVIATION 19.4 | 406.7 millisecconds (ms) STANDARD_DEVIATION 19.4 |
| QTcF interval baseline values 4 h | — | 407.0 millisecconds (ms) STANDARD_DEVIATION 17.8 | 407.0 millisecconds (ms) STANDARD_DEVIATION 17.8 |
| QTcF interval baseline values 5 h | — | 407.2 millisecconds (ms) STANDARD_DEVIATION 18 | 407.2 millisecconds (ms) STANDARD_DEVIATION 18 |
| QTcF interval baseline values -5 minutes | — | 405.2 millisecconds (ms) STANDARD_DEVIATION 19.6 | 405.2 millisecconds (ms) STANDARD_DEVIATION 19.6 |
| QTcF interval baseline values 6 h | — | 405.9 millisecconds (ms) STANDARD_DEVIATION 18.3 | 405.9 millisecconds (ms) STANDARD_DEVIATION 18.3 |
| QTcF interval baseline values 7 h | — | 405.4 millisecconds (ms) STANDARD_DEVIATION 19.2 | 405.4 millisecconds (ms) STANDARD_DEVIATION 19.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 64 Participants | 96 Participants |
| Sex: Female, Male Female | 10 Participants | 20 Participants | 30 Participants |
| Sex: Female, Male Male | 22 Participants | 44 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 50 / 64 | 25 / 32 |
| other Total, other adverse events | 55 / 64 | 27 / 32 |
| serious Total, serious adverse events | 20 / 64 | 11 / 32 |
Outcome results
Primary
Probability Rates of Progression-free Survival at 9 Months
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.
Population: Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib (BIBF 1120) | Probability Rates of Progression-free Survival at 9 Months | 0.431 Probability |
| Sunitinib | Probability Rates of Progression-free Survival at 9 Months | 0.452 Probability |
p-value: 0.8531Normal approximation test
Primary
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)
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.
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 12 h | 1.6 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at -5 minutes (min) | 2.6 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 1 hour (h) | 0.4 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 2 h | -1.7 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 3 h | -0.5 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 4 h | -0.5 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 5 h | 0.3 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 6 h | 2.2 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 7 h | 3.1 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 15 at 10 h | 0.1 milliseconds (ms) |
Secondary
Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at -5 minutes (min) | 164.7 milliseconds (ms) | Standard Deviation 24 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 1 h | 165.7 milliseconds (ms) | Standard Deviation 25.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 2 h | 166.8 milliseconds (ms) | Standard Deviation 25.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 3 h | 166.5 milliseconds (ms) | Standard Deviation 24.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 4 h | 168.0 milliseconds (ms) | Standard Deviation 27.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 5 h | 167.2 milliseconds (ms) | Standard Deviation 26.5 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 6 h | 168.3 milliseconds (ms) | Standard Deviation 26.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 7 h | 168.9 milliseconds (ms) | Standard Deviation 27.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 10 h | 168.1 milliseconds (ms) | Standard Deviation 26.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 12 h | 170.1 milliseconds (ms) | Standard Deviation 29.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at -5 min | 164.5 milliseconds (ms) | Standard Deviation 24.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at 1 h | 166.1 milliseconds (ms) | Standard Deviation 25.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at 2 h | 166.8 milliseconds (ms) | Standard Deviation 26.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at 3 h | 167.4 milliseconds (ms) | Standard Deviation 25.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at 4 h | 168.7 milliseconds (ms) | Standard Deviation 27.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at 5 h | 167.7 milliseconds (ms) | Standard Deviation 27.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15at 6 h | 169.3 milliseconds (ms) | Standard Deviation 26.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at 7 h | 169.0 milliseconds (ms) | Standard Deviation 27.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at 10 h | 169.1 milliseconds (ms) | Standard Deviation 27.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 15 at 12:00 h:min | 168.8 milliseconds (ms) | Standard Deviation 27.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at -5 min | -0.1 milliseconds (ms) | Standard Deviation 10.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at 1 h | 0.5 milliseconds (ms) | Standard Deviation 12.5 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at 2 h | -0.0 milliseconds (ms) | Standard Deviation 12.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at 3 h | 0.9 milliseconds (ms) | Standard Deviation 14.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time matched - change from Day -1 to Day 15 in PR interval at 4 h | 0.9 milliseconds (ms) | Standard Deviation 12.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at 5 h | 0.9 milliseconds (ms) | Standard Deviation 13.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at 6 h | 1.3 milliseconds (ms) | Standard Deviation 11.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at 7 h | 0.6 milliseconds (ms) | Standard Deviation 13.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at 10 h | 1.2 milliseconds (ms) | Standard Deviation 11.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 15 in PR interval at 12 h | -1.5 milliseconds (ms) | Standard Deviation 12.5 |
Secondary
Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 2 h | -0.3 milliseconds (ms) | Standard Deviation 5.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 3 h | -0.8 milliseconds (ms) | Standard Deviation 5.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at -5 minutes (min) | 92.5 milliseconds (ms) | Standard Deviation 11.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 1 hour (h) | 93.8 milliseconds (ms) | Standard Deviation 11.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 2 h | 93.3 milliseconds (ms) | Standard Deviation 10.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 3 h | 93.6 milliseconds (ms) | Standard Deviation 10.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 4 h | 92.7 milliseconds (ms) | Standard Deviation 9.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 5 h | 92.7 milliseconds (ms) | Standard Deviation 11 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 6 h | 92.7 milliseconds (ms) | Standard Deviation 10.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 7 h | 93.1 milliseconds (ms) | Standard Deviation 10.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 10 h | 92.8 milliseconds (ms) | Standard Deviation 11.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 12 h | 92.6 milliseconds (ms) | Standard Deviation 10.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at -5 min | 93.3 milliseconds (ms) | Standard Deviation 11 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value Day 15, 1 h | 93.9 milliseconds (ms) | Standard Deviation 10.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at 2 h | 93.0 milliseconds (ms) | Standard Deviation 11.5 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at 3 h | 92.9 milliseconds (ms) | Standard Deviation 11.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at 4 h | 92.6 milliseconds (ms) | Standard Deviation 11.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at 5 h | 93.6 milliseconds (ms) | Standard Deviation 10.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at 6 h | 93.1 milliseconds (ms) | Standard Deviation 11.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at 7 h | 93.1 milliseconds (ms) | Standard Deviation 11.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at 10 h | 92.8 milliseconds (ms) | Standard Deviation 10.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 15 at 12 h | 93.7 milliseconds (ms) | Standard Deviation 11.5 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at -5 min | 0.8 milliseconds (ms) | Standard Deviation 5.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 1 h | 0.0 milliseconds (ms) | Standard Deviation 5.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 4 h | -0.6 milliseconds (ms) | Standard Deviation 5.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 5 h | 0.5 milliseconds (ms) | Standard Deviation 7.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 6 h | -0.1 milliseconds (ms) | Standard Deviation 5.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 7 h | -0.4 milliseconds (ms) | Standard Deviation 5.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 10 h | 0.1 milliseconds (ms) | Standard Deviation 5.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 15 in QRS interval at 12 h | 1.0 milliseconds (ms) | Standard Deviation 4.7 |
Secondary
Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 10 h | 168.0 milliseconds (ms) | Standard Deviation 26.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 12 h | 0.7 milliseconds (ms) | Standard Deviation 9.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at -5 minutes (min) | 164.7 milliseconds (ms) | Standard Deviation 23.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 1 hour (h) | 165.7 milliseconds (ms) | Standard Deviation 24.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 2 h | 166.8 milliseconds (ms) | Standard Deviation 24.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 3 h | 166.6 milliseconds (ms) | Standard Deviation 24 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 4 h | 168.1 milliseconds (ms) | Standard Deviation 26.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 5 h | 167.2 milliseconds (ms) | Standard Deviation 26.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 6 h | 168.1 milliseconds (ms) | Standard Deviation 26.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 7 h | 168.9 milliseconds (ms) | Standard Deviation 27.5 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day -1 at 12 h | 170.0 milliseconds (ms) | Standard Deviation 29.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at -5 min | 165.7 milliseconds (ms) | Standard Deviation 25.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at 1 h | 167.4 milliseconds (ms) | Standard Deviation 28.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at 2 h | 169.4 milliseconds (ms) | Standard Deviation 28.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at 3 h | 170.0 milliseconds (ms) | Standard Deviation 27.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at 4 h | 170.0 milliseconds (ms) | Standard Deviation 28.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at 5 h | 169.4 milliseconds (ms) | Standard Deviation 27.5 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at 6 h | 170.8 milliseconds (ms) | Standard Deviation 27.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at 7 h | 169.9 milliseconds (ms) | Standard Deviation 27 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value n PR interval on Day 1 at 10 h | 169.8 milliseconds (ms) | Standard Deviation 26.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Absolute value in PR interval on Day 1 at 12 h | 171.3 milliseconds (ms) | Standard Deviation 28.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at -5 min | 0.7 milliseconds (ms) | Standard Deviation 7.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 1 h | 1.7 milliseconds (ms) | Standard Deviation 11.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 2 h | 2.6 milliseconds (ms) | Standard Deviation 10.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 3 h | 3.4 milliseconds (ms) | Standard Deviation 9.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 4 h | 2.2 milliseconds (ms) | Standard Deviation 9.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 5 h | 2.8 milliseconds (ms) | Standard Deviation 10.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 6 h | 3.3 milliseconds (ms) | Standard Deviation 9.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 7 h | 1.6 milliseconds (ms) | Standard Deviation 9.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval | Time-matched change from Day -1 to Day 1 in PR interval at 10 h | 1.8 milliseconds (ms) | Standard Deviation 8.6 |
Secondary
Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at -5 minutes (min) | 92.4 milliseconds (ms) | Standard Deviation 11.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 1 h | 93.7 milliseconds (ms) | Standard Deviation 11 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 2 h | 93.2 milliseconds (ms) | Standard Deviation 10.5 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 3 h | 93.6 milliseconds (ms) | Standard Deviation 10.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 4 h | 92.7 milliseconds (ms) | Standard Deviation 9.8 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 5 h | 92.6 milliseconds (ms) | Standard Deviation 11 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 6 h | 92.5 milliseconds (ms) | Standard Deviation 10.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 7 h | 93.0 milliseconds (ms) | Standard Deviation 10.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1 at 10 h | 92.8 milliseconds (ms) | Standard Deviation 11.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day -1, 12 h | 92.5 milliseconds (ms) | Standard Deviation 10.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at -5 min | 92.6 milliseconds (ms) | Standard Deviation 10.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 1 h | 93.2 milliseconds (ms) | Standard Deviation 11 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 2 h | 93.0 milliseconds (ms) | Standard Deviation 10.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 3 h | 93.3 milliseconds (ms) | Standard Deviation 10.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 4 h | 93.5 milliseconds (ms) | Standard Deviation 11.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 5 h | 93.4 milliseconds (ms) | Standard Deviation 11.5 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 6 h | 93.4 milliseconds (ms) | Standard Deviation 10.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 7 h | 93.2 milliseconds (ms) | Standard Deviation 11.3 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 10 h | 92.3 milliseconds (ms) | Standard Deviation 10.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Absolute value in QRS interval on Day 1 at 12 h | 92.8 milliseconds (ms) | Standard Deviation 10.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval at -5 min | 0.7 milliseconds (ms) | Standard Deviation 5.1 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval at 1 h | -0.5 milliseconds (ms) | Standard Deviation 5.2 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval 2 h | -0.2 milliseconds (ms) | Standard Deviation 4.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval at 3h | -0.3 milliseconds (ms) | Standard Deviation 4.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to day 1 in QRS interval at 4 h | 0.2 milliseconds (ms) | Standard Deviation 4.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval at 5 h | 0.2 milliseconds (ms) | Standard Deviation 5.4 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval at 6 h | 0.3 milliseconds (ms) | Standard Deviation 5.6 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval at 7 h | -0.2 milliseconds (ms) | Standard Deviation 4.7 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval at 10 h | -0.5 milliseconds (ms) | Standard Deviation 4.9 |
| Nintedanib (BIBF 1120) | Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval | Time-matched change from Day -1 to Day 1 in QRS interval at 12 h | 0.3 milliseconds (ms) | Standard Deviation 4.9 |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Averaged time-matched changes from baseline in QT interval over 1 h to 12 h after dosing on Day 1 | 0.9 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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 | Averaged time-matched changes from baseline in QT interval over 1 h to 12 h after dosing on Day 15 | 4.2 millisecond (ms) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Averaged time-matched HR change from baseline over 1 to 12 hours on Day 1 | -1.9 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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 | Averaged time-matched HR change from baseline over 1 to 12 hours on Day 15 | -2.5 beats per minute (bpm) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Averaged time-matched changes from baseline in QTcF interval over 1 h to 12 h after dosing on Day 15 | 0.5 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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 | Averaged time-matched changes from baseline in QTcF interval over 1 h to 12 h after dosing on Day 1 | -2.2 milliseconds (ms) |
Secondary
Duration of Hospital Stays Due to Adverse Events Requiring or Prolonging Hospitalisation
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.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib (BIBF 1120) | Duration of Hospital Stays Due to Adverse Events Requiring or Prolonging Hospitalisation | 11.40 days | Standard Deviation 8.56 |
| Sunitinib | Duration of Hospital Stays Due to Adverse Events Requiring or Prolonging Hospitalisation | 13.10 days | Standard Deviation 8.32 |
Secondary
Duration of Objective Response
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.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib (BIBF 1120) | Duration of Objective Response | 19.42 Months |
| Sunitinib | Duration of Objective Response | 11.66 Months |
Secondary
Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0
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.
Population: Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 2 | 16 Participants |
| Nintedanib (BIBF 1120) | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 4 | 10 Participants |
| Nintedanib (BIBF 1120) | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 3 | 14 Participants |
| Nintedanib (BIBF 1120) | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 5 | 7 Participants |
| Nintedanib (BIBF 1120) | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 1 | 11 Participants |
| Sunitinib | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 5 | 1 Participants |
| Sunitinib | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 1 | 5 Participants |
| Sunitinib | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 2 | 6 Participants |
| Sunitinib | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 3 | 16 Participants |
| Sunitinib | Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 | Grade 4 | 2 Participants |
Secondary
Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1
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.
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Nintedanib (BIBF 1120) | Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 | ECG interpretation on Day 1 | Not normal and new onset of finding | 1 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 | ECG interpretation on Day 1 | Normal | 39 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 | ECG interpretation on Day 1 | Not normal and not normal at baseline | 24 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 | ECG interpretation on Day 15 | Normal | 37 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 | ECG interpretation on Day 15 | Not normal and not normal at baseline | 25 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1 | ECG interpretation on Day 15 | Not normal and new onset of finding | 1 Participants |
Secondary
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
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.
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 1, 1-12 hours (h) | <= 30 milliseconds (ms) | 64 Participants |
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 1, 1-12 hours (h) | > 30 to 60 milliseconds (ms) | 0 Participants |
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 1, 1-12 hours (h) | > 60 milliseconds (ms) | 0 Participants |
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 15, -0:05-12 h | <= 30 milliseconds (ms) | 57 Participants |
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 15, -0:05-12 h | > 30 to 60 milliseconds (ms) | 6 Participants |
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 15, -0:05-12 h | > 60 milliseconds (ms) | 0 Participants |
Secondary
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
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.
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 1, 1-12 hour (h) | <= 60 milliseconds (ms) | 64 Participants |
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 1, 1-12 hour (h) | > 60 milliseconds (ms) | 0 Participants |
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 15, -0:05-12 h | <= 60 milliseconds (ms) | 62 Participants |
| Nintedanib (BIBF 1120) | 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 | Frequency of patients with maximum time-matched QTcF change from baseline on Day 15, -0:05-12 h | > 60 milliseconds (ms) | 1 Participants |
Secondary
Frequency of Patients With Possible Clinically Significant Abnormal Lab Values
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.
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Haemoglobin | 6 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Sodium | 14 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Alkaline phosphatase | 2 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Neutrophils | 3 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Prothrombin time (PT)-international normalized ratio (INR) | 5 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Platelets | 2 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Creatinine | 4 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Aspartate amino Transferase (AST) | 10 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Potassium | 14 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Alanine aminotransferase (ALT) | 14 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | APTT (Activated partial thrombopl. time) | 7 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Bilirubin, total | 4 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Lymphocytes | 8 Participants |
| Nintedanib (BIBF 1120) | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | White blood cell count | 0 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Lymphocytes | 11 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Alkaline phosphatase | 3 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | APTT (Activated partial thrombopl. time) | 0 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Creatinine | 5 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Haemoglobin | 6 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Prothrombin time (PT)-international normalized ratio (INR) | 0 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Potassium | 4 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | White blood cell count | 7 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Sodium | 3 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Neutrophils | 9 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Platelets | 3 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Aspartate amino Transferase (AST) | 1 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Alanine aminotransferase (ALT) | 3 Participants |
| Sunitinib | Frequency of Patients With Possible Clinically Significant Abnormal Lab Values | Bilirubin, total | 3 Participants |
Secondary
Number of Participants With Adverse Events Leading to Discontinuation of Trial Drug
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.
Population: Treated Set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nintedanib (BIBF 1120) | Number of Participants With Adverse Events Leading to Discontinuation of Trial Drug | 11 Participants |
| Sunitinib | Number of Participants With Adverse Events Leading to Discontinuation of Trial Drug | 5 Participants |
Secondary
Number of Participants With Adverse Events Leading to Dose Reduction
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.
Population: Treated Set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nintedanib (BIBF 1120) | Number of Participants With Adverse Events Leading to Dose Reduction | 16 Participants |
| Sunitinib | Number of Participants With Adverse Events Leading to Dose Reduction | 8 Participants |
Secondary
Number of Participants With Adverse Events Requiring or Prolonging Hospitalisation
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.
Population: Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nintedanib (BIBF 1120) | Number of Participants With Adverse Events Requiring or Prolonging Hospitalisation | 15 Participants |
| Sunitinib | Number of Participants With Adverse Events Requiring or Prolonging Hospitalisation | 10 Participants |
Secondary
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
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.
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Number of participants with new onset of QTcF ≤450 (ms) on Day 1 | 3 Participants |
| Nintedanib (BIBF 1120) | 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 | Number of participants with new onset of QTcF ≤450 (ms) on Day 15 | 2 Participants |
Secondary
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
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.
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Number of participants with new onset of QTcF >450 to 470 ms on Day 1 | 1 Participants |
| Nintedanib (BIBF 1120) | 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 | Number of participants with new onset of QTcF >450 to 470 ms on Day 15 | 1 Participants |
Secondary
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
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.
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Number of participants with new onset of QTcF> 500 (ms) on Day 1, 1-12 hour (h) | 0 Participants |
| Nintedanib (BIBF 1120) | 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 | Number of participants with new onset of QTcF> 500 (ms) (notable prolongation) on Day 15, -0:05-12 h | 0 Participants |
Secondary
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
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.
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Number of participants with new onset of QT> 500 (ms) on Day 1, 1-12 hour (h) | 0 Participants |
| Nintedanib (BIBF 1120) | 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 | Number of participants with new onset of QT> 500 (ms) on Day 15, -0:05-12 h | 0 Participants |
Secondary
Number of Participants With New Onset of QTcF> 470 to 500 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 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 (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.
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | Number of Participants With New Onset of QTcF> 470 to 500 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 | Number of participants with new onset of QTcF> 470 to 500 ms on Day 1 | 0 Participants |
| Nintedanib (BIBF 1120) | Number of Participants With New Onset of QTcF> 470 to 500 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1 | Number of participants with new onset of QTcF> 470 to 500 ms on Day 15 | 1 Participants |
Secondary
Objective Response According to RECIST Criteria
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.
Population: Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | Objective Response According to RECIST Criteria | Complete Response | 0 Participants |
| Nintedanib (BIBF 1120) | Objective Response According to RECIST Criteria | Partial response | 14 Participants |
| Sunitinib | Objective Response According to RECIST Criteria | Complete Response | 1 Participants |
| Sunitinib | Objective Response According to RECIST Criteria | Partial response | 11 Participants |
Comparison: 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.p-value: 0.121395% CI: [0.193, 1.212]Regression, Logistic
Secondary
Overall Survival
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.
Population: Treated Set (TS) : All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib (BIBF 1120) | Overall Survival | 20.37 Months |
| Sunitinib | Overall Survival | 21.22 Months |
p-value: 0.759395% CI: [0.542, 1.564]Log Rank
Secondary
Progression Free Survival (PFS)
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.
Population: Treated set: all patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib (BIBF 1120) | Progression Free Survival (PFS) | 8.44 Months |
| Sunitinib | Progression Free Survival (PFS) | 8.38 Months |
Comparison: 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).p-value: 0.639595% CI: [0.697, 1.8]Log Rank
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in HR at maximum BIBF 1120 concentration on Day 1 | -2.0 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in HR at maximum BIBF 1120 concentration on Day 15 | -2.1 beats per minute (bpm) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in HR at maximum BIBF 1202 concentration on Day 1 | -2.3 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in HR at maximum BIBF 1202 concentration on Day 15 | -2.0 beats per minute (bpm) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in HR at maximum BIBF 1202-glucuronide concentration on Day 1 | -1.2 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in HR at maximum BIBF 1202-glucuronide concentration on Day 15 | -1.6 beats per minute (bpm) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QTcF interval at maximum BIBF 1202 concentration on Day 1 | -2.5 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QTcF interval at maximum BIBF 1202 concentration on Day 15 | -1.1 milliseconds (ms) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change in QTcF from baseline at maximum BIBF 1202-glucuronide concentration on Day 1 | -2.4 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change in QTcF from baseline at maximum BIBF 1202-glucuronide concentration on Day 15 | -1.5 milliseconds (ms) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QTcF interval at maximum BIBF 1120 concentration on Day 15 | -3.2 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QTcF interval at maximum BIBF 1120 concentration on Day 1 | -2.8 milliseconds (ms) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QT at maximum BIBF 1202-glucuronide concentration on Day 1 | -0.4 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QT at maximum BIBF 1202-glucuronide concentration on Day 15 | 1.3 millisecond (ms) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QT interval at maximum BIBF 1202 concentration on Day 1 | 1.2 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QT interval at maximum BIBF 1202 concentration on Day 15 | 1.8 millisecond (ms) |
Secondary
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
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.
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QT interval at maximum BIBF 1120 concentration on Day 1 | 0.9 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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 | Time-matched change from baseline in QT interval at maximum BIBF 1120 concentration on Day 15 | -0.4 millisecond (ms) |
Secondary
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)
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.
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 1 hour (h) | -1.6 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 2 h | -3.1 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 3 h | -2.6 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 4 h | -2.6 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 5 h | -1.4 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 6 h | -2.0 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 7 h | -1.5 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 10 h | -3.6 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched change from baseline to Day 1 at 12 h | -2.2 milliseconds (ms) |
Secondary
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)
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.
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 1 hour (h) | 0.5 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 6 h | 7.7 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 7 h | 7.1 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 10 h | 3.4 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 12 h | 4.2 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at -5 minutes (min) | 1.0 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 2 h | 1.6 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 3 h | 4.4 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 4 h | 4.7 milliseconds (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 15 at 5 h | 5.1 milliseconds (ms) |
Secondary
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)
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.
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 2 h | 1.6 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 12 h | -2.2 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 1 hour (h) | -2.0 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 3 h | 3.5 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 4 h | 1.4 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 5 h | 1.4 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 6 h | 1.8 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 7 h | 0.7 millisecond (ms) |
| Nintedanib (BIBF 1120) | 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) | Time-matched QT interval change from baseline to Day 1 at 10 h | -1.7 millisecond (ms) |
Secondary
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)
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.
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 5 h | -3.1 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 6 h | -3.8 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 7 h | -2.8 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at -5 minutes (min) | 0.9 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 1 h | -0.3 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 2 h | -2.0 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 3 h | -3.3 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 4 h | -3.4 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 10 h | -2.4 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 15 at 12 h | -1.6 beats per minute (bpm) |
Secondary
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)
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.
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 7 h | -1.4 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 10 h | -1.3 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 12 h | 0.0 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 1 hour (h) | -0.0 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 2 h | -2.9 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 3 h | -3.8 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 4 h | -2.5 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 5 h | -1.8 beats per minute (bpm) |
| Nintedanib (BIBF 1120) | 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) | Time-matched heart rate (HR) change from baseline to Day 1 at 6 h | -2.2 beats per minute (bpm) |
Secondary
Time to Progression
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.
Population: Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib (BIBF 1120) | Time to Progression | 8.48 Months |
| Sunitinib | Time to Progression | 8.54 Months |
p-value: 0.595895% CI: [0.697, 1.873]Log Rank
Secondary
Time to Treatment Failure
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.
Population: Treated set (TS): All patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib (BIBF 1120) | Time to Treatment Failure | 8.44 Month |
| Sunitinib | Time to Treatment Failure | 8.36 Month |
p-value: 0.571295% CI: [0.72, 1.812]Log Rank