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Investigation of Food Effect and Gastric ph Increase on the Bioavailability of Faldapravir

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ClinicalTrials.gov Identifier: NCT01694706
Recruitment Status : Completed
First Posted : September 27, 2012
Results First Posted : July 30, 2015
Last Update Posted : July 30, 2015
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: faldaprevir
Drug: omeprazole
Enrollment 15
Recruitment Details  
Pre-assignment Details This was a randomised open label, 3-way cross over study with three sequences. Faldaprevir administrations in each treatment period were separated by washout period of at least 14 days.
Arm/Group Title Faldaprevir/Faldaprevir+ OMP/Faldaprevir Fed Faldaprevir Fed/ Faldaprevir/ Faldaprevir+ OMP Faldaprevir+ OMP/ Faldaprevir Fed/ Faldaprevir
Hide Arm/Group Description

Faldaprevir: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration.

Faldaprevir+ OMP: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast prior the drug administration following multiple dosing of 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir.

Faldaprevir fed: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less.

Faldaprevir fed: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less.

Faldaprevir: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration (Reference treatment)

faldaprevir+ OMP: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast prior the drug administration following multiple dosing of 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir.

Faldaprevir+ OMP: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast prior the drug administration following multiple dosing of 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir.

Faldaprevir fed: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less.

Faldaprevir: Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration
Period Title: Overall Study
Started 5 5 5
Received Faldaprevir 5 5 5
Received Faldaprevir +OMP 5 5 5
Received Faldaprevir Fed 4 5 5
Completed 4 4 5
Not Completed 1 1 0
Reason Not Completed
Adverse Event             0             1             0
other reason not defined above             1             0             0
Arm/Group Title Entire Study Population
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All subjects received all tested treatments in a randomised, open label, 3-way cross over study. The treatments were:

Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration (Reference treatment)

Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less.

Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast prior the drug administration following multiple dosing of 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir.

Drug administrations were separated by a washout period of at least 14 days
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
Treated set (TS) including all subjects who received at least 1 dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
34.7  (8.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
7
  46.7%
Male
8
  53.3%
1.Primary Outcome
Title Faldaprevir: Area Under the Curve Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity)
Hide Description

Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 extrapolated to infinity

In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time Frame 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration
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Pharmacokinetic (PK) set: Included all treated subjects that provided at least 1 observation for at least 1 primary endpoint without important protocol violations with respect to the statistical evaluation of the pharmacokinetic endpoints.
Arm/Group Title Faldaprevir in Fasting Faldaprevir After a High-fat Meal Faldaprevir and Omeprazole
Hide Arm/Group Description:
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration (Reference treatment)
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast prior the drug administration following multiple dosing of 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir
Overall Number of Participants Analyzed 14 14 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: [ng*h/mL]
37900
(67.2%)
48200
(41.7%)
36000
(63.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Faldaprevir in Fasting, Faldaprevir After a High-fat Meal
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments no formal testing, investigation of bioavailability
Statistical Test of Hypothesis P-Value 0.3420
Comments [Not Specified]
Method ANOVA
Comments Ratio calculated as Faldaprevir after a high-fat meal divided by Faldaprevir in fasting
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 120.35
Confidence Interval (2-Sided) 90%
102.09 to 141.88
Parameter Dispersion
Type: Standard Deviation
Value: 23.2
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Faldaprevir in Fasting, Faldaprevir and Omeprazole
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments no formal testing, investigation of bioavailability
Statistical Test of Hypothesis P-Value 0.0962
Comments [Not Specified]
Method ANOVA
Comments Ratio calculated as Faldaprevir and Omeprazole divided by Faldaprevir in fasting
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 94.33
Confidence Interval (2-Sided) 90%
76.21 to 116.76
Parameter Dispersion
Type: Standard Deviation
Value: 30.8
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
2.Primary Outcome
Title Faldaprevir: Maximum Measured Concentration (Cmax)
Hide Description

Maximum measured concentration of the faldaprevir in plasma

In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time Frame 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration
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Hide Analysis Population Description
PK set
Arm/Group Title Faldaprevir in Fasting Faldaprevir After a High-fat Meal Faldaprevir and Omeprazole
Hide Arm/Group Description:
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration (Reference treatment)
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast prior the drug administration following multiple dosing of 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir
Overall Number of Participants Analyzed 14 14 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
2030
(140%)
2600
(57.5%)
1920
(122%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Faldaprevir in Fasting, Faldaprevir After a High-fat Meal
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments no formal testing, investigation of bioavailability
Statistical Test of Hypothesis P-Value 0.3993
Comments [Not Specified]
Method ANOVA
Comments Ratio calculated as Faldaprevir after a high-fat meal divided by Faldaprevir in fasting
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 118.79
Confidence Interval (2-Sided) 90%
83.190 to 169.628
Parameter Dispersion
Type: Standard Deviation
Value: 52.4
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Faldaprevir in Fasting, Faldaprevir and Omeprazole
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments no formal testing, investigation of bioavailability
Statistical Test of Hypothesis P-Value 0.2204
Comments [Not Specified]
Method ANOVA
Comments Ratio calculated as Faldaprevir and Omeprazole divided by Faldaprevir in fasting
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 93.55
Confidence Interval (2-Sided) 90%
65.783 to 133.030
Parameter Dispersion
Type: Standard Deviation
Value: 53.0
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
3.Secondary Outcome
Title Faldaprevir: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
Hide Description

Area under the concentration-time curve of the faldaprevir in plasma over the time interval from 0 to the last quantifiable drug plasma concentration

In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time Frame 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h and 120h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PK set
Arm/Group Title Faldaprevir in Fasting Faldaprevir After a High-fat Meal Faldaprevir and Omeprazole
Hide Arm/Group Description:
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration (Reference treatment)
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less
Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast prior the drug administration following multiple dosing of 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir
Overall Number of Participants Analyzed 14 14 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
36300
(70.3%)
46400
(42.6%)
34400
(65.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Faldaprevir in Fasting, Faldaprevir After a High-fat Meal
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments no formal testing, investigation of bioavailability
Statistical Test of Hypothesis P-Value 0.3765
Comments [Not Specified]
Method ANOVA
Comments Ratio calculated as Faldaprevir after a high-fat meal divided by Faldaprevir in fasting
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 121.28
Confidence Interval (2-Sided) 90%
102.32 to 143.74
Parameter Dispersion
Type: Standard Deviation
Value: 24.0
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Faldaprevir in Fasting, Faldaprevir and Omeprazole
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments no formal testing, investigation of bioavailability
Statistical Test of Hypothesis P-Value 0.0946
Comments [Not Specified]
Method ANOVA
Comments Ratio calculated as Faldaprevir and Omeprazole divided by Faldaprevir in fasting
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 94.72
Confidence Interval (2-Sided) 90%
76.25 to 117.67
Parameter Dispersion
Type: Standard Deviation
Value: 31.4
Estimation Comments Standard deviation is actually the geometric coefficient of variation (gCV)
Time Frame From first drug administration until the end of trial visit, up until 20 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Faldaprevir in Fasting Faldaprevir After a High-fat Meal Faldaprevir and Omeprazole Omeprazole
Hide Arm/Group Description Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally following an overnight or at least 10 hours (h) fast prior the drug administration (Reference treatment) Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was administered orally 30 minutes (min) after a standard high-fat, high-caloric meal was served. The meal had to be completely consumed within 25 min or less Single dose of 240 mg faldaprevir in a form of two soft gelatin capsules was coadministered orally with 40 mg Omeprazole following an overnight or at least 10 hours (h) fast 40 mg omeprazole once daily for 4 days prior the first dose of faldaprevir
All-Cause Mortality
Faldaprevir in Fasting Faldaprevir After a High-fat Meal Faldaprevir and Omeprazole Omeprazole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Faldaprevir in Fasting Faldaprevir After a High-fat Meal Faldaprevir and Omeprazole Omeprazole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/14 (0.00%)   0/14 (0.00%)   0/15 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Faldaprevir in Fasting Faldaprevir After a High-fat Meal Faldaprevir and Omeprazole Omeprazole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/15 (26.67%)   4/14 (28.57%)   4/14 (28.57%)   0/15 (0.00%) 
Gastrointestinal disorders         
Abdominal pain upper † 1  0/15 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  0/15 (0.00%) 
Diarrhoea † 1  2/15 (13.33%)  0/14 (0.00%)  2/14 (14.29%)  0/15 (0.00%) 
Nausea † 1  0/15 (0.00%)  0/14 (0.00%)  1/14 (7.14%)  0/15 (0.00%) 
Vomiting † 1  1/15 (6.67%)  0/14 (0.00%)  0/14 (0.00%)  0/15 (0.00%) 
Infections and infestations         
Rhinitis † 1  0/15 (0.00%)  0/14 (0.00%)  1/14 (7.14%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthritis † 1  1/15 (6.67%)  0/14 (0.00%)  0/14 (0.00%)  0/15 (0.00%) 
Nervous system disorders         
Headache † 1  1/15 (6.67%)  2/14 (14.29%)  0/14 (0.00%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asthma † 1  0/15 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  0/15 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.1
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01694706     History of Changes
Other Study ID Numbers: 1220.59
2012-002941-39 ( EudraCT Number: EudraCT )
First Submitted: September 24, 2012
First Posted: September 27, 2012
Results First Submitted: July 3, 2015
Results First Posted: July 30, 2015
Last Update Posted: July 30, 2015