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Relative Bioavailability of a Single Dose of Nintedanib Given Alone and in Combination With Multiple Doses of Rifampicin

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ClinicalTrials.gov Identifier: NCT01770392
Recruitment Status : Completed
First Posted : January 17, 2013
Results First Posted : November 27, 2014
Last Update Posted : November 27, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Nintedanib
Drug: Rifampicin
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Overall Study
Hide Arm/Group Description This was an open-label, two-period, fixed-sequence trial. During the first period 150 mg of nintedanib was administered orally in form of a soft gelatine capsule. In the second period, a single dose of 600 mg of rifampicin was administered orally via film-coated tablet every day for a week, then a single dose of nintedanib was administered. The administrations of nintedanib were separated by a washout period of at least 14 days.
Period Title: Nintedanib
Started 26
Completed 26
Not Completed 0
Period Title: Washout Period of at Least 14 Days
Started 26
Completed 25
Not Completed 1
Reason Not Completed
Adverse Event             1
Period Title: Nintedanib+ Rifampicin
Started 25
Completed 25
Not Completed 0
Arm/Group Title Overall Study
Hide Arm/Group Description This was an open-label, two-period, fixed-sequence trial. During the first period 150 mg of nintedanib was administered orally in form of a soft gelatine capsule. In the second period, a single dose of 600 mg of rifampicin was administered orally via film-coated tablet every day for a week, then a single dose of nintedanib was administered. The administrations of nintedanib were separated by a washout period of at least 14 days.
Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
The treated set (TS) consists of all subjects who took at least one dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
37.3  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
0
   0.0%
Male
26
 100.0%
1.Primary Outcome
Title Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞)
Hide Description

AUC0-∞ represents the Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity.

For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib
Hide Outcome Measure Data
Hide Analysis Population Description
TS
Arm/Group Title Nintedanib Nintedanib + Rifampicin
Hide Arm/Group Description:
150 mg of nintedanib was given as a single dose on Day 1.
600 mg rifampicin was given every evening from Day -7 to Day -1, followed by a single dose of 150 mg nintedanib in the morning of Day 1.
Overall Number of Participants Analyzed 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
183
(36.1%)
89.4
(36.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib, Nintedanib + Rifampicin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments p-value for ratio outside interval 0.8 - 1.25
Method ANOVA
Comments The model includes fixed effect for treatment and effect "subjects" was considered as random
Method of Estimation Estimation Parameter Geometric Mean Ratio in percentage
Estimated Value 50.12
Confidence Interval (2-Sided) 90%
47.155 to 53.275
Parameter Dispersion
Type: Standard Deviation
Value: 12.7
Estimation Comments

The standard deviation is actually the geometric coefficient of variation (in %).

The ratio has been calculated as (nintedanib+ rifampicin) divided by nintedanib (in %)

2.Primary Outcome
Title Maximum Measured Concentration (Cmax)
Hide Description Cmax represents the maximum concentration of nintedanib in plasma. For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time Frame 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib
Hide Outcome Measure Data
Hide Analysis Population Description
TS
Arm/Group Title Nintedanib Nintedanib + Rifampicin
Hide Arm/Group Description:
150 mg of Nintedanib was given as a single dose on Day 1.
600 mg Rifampicin was given every evening from Day -7 to Day -1, followed by a single dose of 150 mg nintedanib in the morning of Day 1.
Overall Number of Participants Analyzed 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
22.1
(51.8%)
12.8
(43.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib, Nintedanib + Rifampicin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments p-value for ratio outside interval 0.8 - 1.25
Method ANOVA
Comments The model includes fixed effect for treatment and effect "subjects" was considered as random
Method of Estimation Estimation Parameter Geometric Mean Ratio in percentage
Estimated Value 59.76
Confidence Interval (2-Sided) 90%
53.829 to 66.348
Parameter Dispersion
Type: Standard Deviation
Value: 21.9
Estimation Comments

The standard deviation is actually the geometric coefficient of variation (in %).

The ratio has been calculated as (nintedanib+ rifampicin) divided by nintedanib (in %).

3.Secondary Outcome
Title Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz)
Hide Description

AUC0-tz represents the area under the plasma concentration-time curve of nintedanib from 0 to the last quantifiable analyte plasma concentration.

For this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Time Frame 1.5 hour (h) before the first drug administration and 0.5h, 1h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after administration of nintedanib
Hide Outcome Measure Data
Hide Analysis Population Description
TS
Arm/Group Title Nintedanib Nintedanib + Rifampicin
Hide Arm/Group Description:
150 mg of nintedanib was given as a single dose on Day 1.
600 mg rifampicin was given every evening from Day -7 to Day -1, followed by a single dose of 150 mg nintedanib in the morning of Day 1.
Overall Number of Participants Analyzed 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
173
(36.9%)
84.1
(38.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib, Nintedanib + Rifampicin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments p-value for ratio outside interval 0.8 - 1.25
Method ANOVA
Comments The model includes fixed effect for treatment and effect "subjects" was considered as random
Method of Estimation Estimation Parameter Geometric Mean Ratio in percentage
Estimated Value 49.98
Confidence Interval (2-Sided) 90%
46.886 to 53.286
Parameter Dispersion
Type: Standard Deviation
Value: 13.3
Estimation Comments

The standard deviation is actually the geometric coefficient of variation (in %).

The ratio has been calculated as (nintedanib+ rifampicin) divided by nintedanib (in %).

Time Frame From the first trial drug administration until up to 14 days after last trial drug administration, up to 28 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Nintedanib Washout Period Rifampicin Nintedanib + Rifampicin
Hide Arm/Group Description 150 mg of nintedanib was given as a single dose on Day 1. washout period of at least 14 days between the administrations of nintedanib. During this period no trial drug was administered 600 mg rifampicin was given every evening from Day -7 to Day -1 600 mg rifampicin was given every evening from Day -7 to Day -1, followed by a single dose of 150 mg nintedanib in the morning of Day 1.
All-Cause Mortality
Nintedanib Washout Period Rifampicin Nintedanib + Rifampicin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Nintedanib Washout Period Rifampicin Nintedanib + Rifampicin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/26 (0.00%)   0/25 (0.00%)   0/25 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nintedanib Washout Period Rifampicin Nintedanib + Rifampicin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/26 (19.23%)   2/26 (7.69%)   25/25 (100.00%)   4/25 (16.00%) 
Gastrointestinal disorders         
Diarrhoea  1  5/26 (19.23%)  0/26 (0.00%)  1/25 (4.00%)  3/25 (12.00%) 
Faeces discoloured  1  0/26 (0.00%)  0/26 (0.00%)  3/25 (12.00%)  0/25 (0.00%) 
Flatulence  1  0/26 (0.00%)  0/26 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
General disorders         
Fatigue  1  0/26 (0.00%)  0/26 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Nervous system disorders         
Dizziness  1  0/26 (0.00%)  0/26 (0.00%)  2/25 (8.00%)  0/25 (0.00%) 
Headache  1  1/26 (3.85%)  2/26 (7.69%)  5/25 (20.00%)  2/25 (8.00%) 
Renal and urinary disorders         
Chromaturia  1  0/26 (0.00%)  0/26 (0.00%)  25/25 (100.00%)  0/25 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01770392     History of Changes
Other Study ID Numbers: 1199.162
2012-002507-18 ( EudraCT Number: EudraCT )
First Submitted: January 15, 2013
First Posted: January 17, 2013
Results First Submitted: November 14, 2014
Results First Posted: November 27, 2014
Last Update Posted: November 27, 2014