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Compare Safety and Efficacy of BIBF 1120 Versus Sunitinib.

Primary Purpose

Carcinoma, Renal Cell

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

BIBF 1120

sunitinib

About this trial

This is an interventional treatment trial for Carcinoma, Renal Cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Patients with unresectable or metastatic Renal Cell Cancer, who have received no previous systemic anti-cancer treatment.
Histological-confirmed diagnosis of renal cell cancer with clear cell component.
Acceptable renal,liver,cardiovascular,bone marrow and other functions to allow sunitinib/BIBF 1120 treatment.

Exclusion criteria:

Patients unable to tolerate Sunitinib/BIBF 1120 treatment
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.
Patients unable to comply with the 1199.26 protocol.
Pregnancy or breast feeding.
Active alcohol or drug abuse.
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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Nintedanib (BIBF 1120)

sunitinib

Arm Description

Non-marketed substance: Twice daily oral doses of 200mg BIBF 1120 given continuously.

Marketed substance: Once a day oral doses of 50mg sunitinib given in repeated 6 week cycles: 4 weeks active, 2 weeks rest.

Outcomes

Primary Outcome Measures

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-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.

Secondary Outcome Measures

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.

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.

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.

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 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 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-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-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-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-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.

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-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-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-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-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-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.

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-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-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-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-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-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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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).

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.

Full Information

NCT ID

NCT01024920

First Posted

November 24, 2009

Last Updated

June 16, 2021

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01024920

Brief Title

Compare Safety and Efficacy of BIBF 1120 Versus Sunitinib.

Official Title

A Randomised, Open Label, Parallel Group Phase II Study Comparing the Efficacy and Tolerability of BIBF 1120 Versus Sunitinib in Previously Untreated Patients With Renal Cell Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Completed

Study Start Date

December 16, 2009 (undefined)

Primary Completion Date

November 8, 2011 (Actual)

Study Completion Date

June 19, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Renal Cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

99 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nintedanib (BIBF 1120)

Arm Type

Experimental

Arm Description

Non-marketed substance: Twice daily oral doses of 200mg BIBF 1120 given continuously.

Arm Title

sunitinib

Arm Type

Active Comparator

Arm Description

Marketed substance: Once a day oral doses of 50mg sunitinib given in repeated 6 week cycles: 4 weeks active, 2 weeks rest.

Intervention Type

Drug

Intervention Name(s)

BIBF 1120

Intervention Description

VEGF inhibitor

Intervention Type

Drug

Intervention Name(s)

sunitinib

Intervention Description

VEGF inhibitor

Primary Outcome Measure Information:

Title

Probability Rates of Progression-free Survival at 9 Months

Description

Time Frame

At 9 months after randomisation.

Title

Description

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.

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

Time Frame

From the start of study until the cut-off date for 3 year efficacy analysis, up to 3 years.

Title

Objective Response According to RECIST Criteria

Description

Time Frame

From the start of study until the cut-off date for 3 year efficacy analysis, up to 3 years.

Title

Duration of Objective Response

Description

Time Frame

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

Title

Overall Survival

Description

Time Frame

From randomisation to death, up to 3 years.

Title

Time to Progression

Description

Time Frame

From randomisation up to objective tumour progression, up to 3 years.

Title

Time to Treatment Failure

Description

Time Frame

From randomisation up to objective tumour progression, up to 3 years.

Title

Description

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

Time Frame

At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 of treatment Cycle 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.

Title

Description

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.

Title

Description

Time Frame

Title

Description

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

Time Frame

Title

Average Time-matched Changes From Baseline in QTcF Interval Over 1 h to 12 h After Dosing on Days 1 and 15 of Treatment Cycle 1

Description

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.

Title

Time-matched Changes From Baseline to Day 15 in QT Interval at 0 Hour (h), at 1 h, at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)

Description

Time Frame

Title

Time-matched Changes From Baseline to Day 1 in QT Interval at 1 Hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)

Description

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

Time Frame

At 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1. Baseline (Day -1) values were taken at exactly the same time points as on Day 1.

Title

Time-Matched Change From Baseline in QT Interval at the Time of Each Patient's Maximum Plasma Concentration of Nintedanib (BIBF 1120), Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

Time Frame

Title

Description

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

Time Frame

At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of first treatment cycle. Continues in the description.

Title

Description

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

Time Frame

Title

Description

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.

Title

Time-Matched Heart Rate (HR) Changes From Baseline to Day 15 at 0 Hour (h), at 1 h, at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)

Description

Time Frame

Title

Time-Matched Heart Rate (HR) Changes From Baseline to Day 1 at 1 Hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h After Dosing of Nintedanib (BIBF 1120)

Description

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

Time Frame

Title

Time-Matched Change From Baseline in Heart Rate (HR) at the Time of Each Patient's Maximum Nintedanib (BIBF 1120) Plasma Concentration, Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

Time Frame

Title

Description

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

Time Frame

Title

Description

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

Time Frame

At 5 minutes (min) before the first dose on Day 15 and at 1 hour (h), at 2 h, at 3 h, at 4 h, at 5 h, at 6 h, at 7 h, at 10 h and at 12 h after the first dose of nintedanib on Day 1 and on Day 15 of treatment cycle 1. Continues in the description.

Title

Averaged Time-Matched Heart Rate (HR) Change From Baseline Over 1 to 12 Hours, Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

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.

Title

Frequency of Patients With Maximum Time-Matched QTcF Interval Change From Baseline Categorized by Magnitude of Change, Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

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

Time Frame

Title

Description

Time Frame

Title

Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF ≤450 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

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

Time Frame

Title

Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF >450 to 470 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

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

Time Frame

Title

Number of Participants With New Onset of QTcF> 470 to 500 Milliseconds (ms), Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

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

Time Frame

Title

Number of Participants With New (Not Present at Any Time Pre-dose) Onset of QTcF> 500 Milliseconds (ms) (Notable Prolongation), Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

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

Time Frame

Title

Description

Time Frame

Title

Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in PR Interval

Description

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.

Title

Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in PR Interval

Description

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

Time Frame

Title

Absolute Values at Baseline (Day -1) and Day 1 and Changes From Baseline to Day 1 at Each Point in Time in QRS Interval

Description

Time Frame

Title

Absolute Values at Baseline (Day -1) and Day 15 and Changes From Baseline to Day 15 at Each Point in Time in QRS Interval

Description

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

Time Frame

Title

Frequency of Patients by Clinical Electrocardiogram (ECG) Measurement Interpretation, Calculated Separately for Days 1 and 15 of Treatment Cycle 1

Description

Time Frame

Title

Frequency of Adverse Events Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0

Description

Time Frame