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Investigation of Faldaprevir Effect on Pharmacokinetics of Raltegravir

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ClinicalTrials.gov Identifier: NCT01785160
Recruitment Status : Completed
First Posted : February 7, 2013
Results First Posted : August 3, 2015
Last Update Posted : August 3, 2015
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Raltegravir
Drug: Faldaprevir
Enrollment 25
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Overall Study
Hide Arm/Group Description Total number of patients randomised and treated in the study.This was a open label trial with two periods in a fixed sequence. All subjects were to receive the following 2 treatments, A]Raltegravir B]Raltegravir+Faldaprevir. The two treatments were separated by washout period of at least 7 days.
Period Title: Treatment Period 1: Raltegravir
Started 25
Completed 24
Not Completed 1
Reason Not Completed
Not treated             1
Period Title: Washout Period of at Least 7 Days
Started 24
Completed 23
Not Completed 1
Reason Not Completed
Consent withdrawn             1
Period Title: Treatment Period 2: Raltegravir + Faldap
Started 23
Completed 23
Not Completed 0
Arm/Group Title Overall Study
Hide Arm/Group Description Total number of patients randomised and treated in the study.This was a open label trial with two periods in a fixed sequence. All subjects were to receive the following 2 treatments, A]Raltegravir B]Raltegravir+Faldaprevir The two treatments were separated by washout period of at least 7 days.
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
The total number of participants N analysed for baseline characteristics is not same as the number of participants enrolled as one subject was not treated after being enrolled
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
40.8  (8.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
12
  50.0%
Male
12
  50.0%
1.Primary Outcome
Title AUC( Tau,ss)
Hide Description

AUC tau,ss (area under the concentration-time curve of the Raltegravir in plasma at steady state over the uniform dosing interval tau) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of AUC tau,ss and their 2-sided 90% confidence intervals (CI) were calculated.

The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for ‘subject’ and ‘treatment’.

RAL: Raltegravir , FDV: Faldaprevir

Time Frame 0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132 hours after RAL and FDV administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic(PK) set:Subjects who received atleast 1 dose of study medication and who provided at least 1 observation for at least 1 PK endpoint without any important protocol violations relevant to the evaluation of relative bioavailability and did not experience emesis at or before 2 times median tmax on the pk study days of both trial periods
Arm/Group Title Raltegravir Raltegravir + Faldaprevir
Hide Arm/Group Description:

Raltegravir coated tablets

Oral with 240 mL of water Days 1 to 3: 400 mg raltegravir twice daily Day 4: 400 mg raltegravir once daily

Raltegravir coated tablets and Faldaprevir soft gelatin capsules

Oral with 240 mL of water Day 1: 400 mg raltegravir twice daily and 240 mg faldaprevir twice daily (loading dose) Days 2 to 5: 400 mg raltegravir twice daily and 240 mg faldaprevir once daily Day 6: 400 mg raltegravir once daily and 240 mg faldaprevir once daily

Overall Number of Participants Analyzed 24 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
4070
(92.9%)
11100
(78.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Raltegravir, Raltegravir + Faldaprevir
Comments Ratio Raltegravir plus Faldaprevir and Raltegravir for the category Raltegravir
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability (No formal testing was performed)
Statistical Test of Hypothesis P-Value 0.9999
Comments P-value for ratio outside interval 0.8-1.25
Method ANOVA
Comments Adjusted geometric mean ratio
Method of Estimation Estimation Parameter Adjusted Geometric Mean ratio
Estimated Value 272.06
Confidence Interval 95%
199.69 to 370.66
Parameter Dispersion
Type: Standard Deviation
Value: 67.9
Estimation Comments The standard deviation is actually the geometric coefficient of variation
2.Primary Outcome
Title Cmax ,ss
Hide Description

C max,ss (maximum measured concentration of the Raltegravir in plasma at steady state) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of Cmax,ss and their 2-sided 90% confidence intervals (CI) were calculated.

The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for ‘subject’ and ‘treatment’.

RAL: Raltegravir , FDV: Faldaprevir

Time Frame 0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132hours after RAL and FDV administration
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic(PK) set:Subjects who received atleast 1 dose of study medication and who provided at least 1 observation for at least 1 PK endpoint without any important protocol violations relevant to the evaluation of relative bioavailability and did not experience emesis at or before 2 times median tmax on the pk study days of both trial periods
Arm/Group Title Raltegravir Raltegravir + Faldaprevir
Hide Arm/Group Description:

Raltegravir coated tablets

Oral with 240 mL of water Days 1 to 3: 400 mg raltegravir twice daily Day 4: 400 mg raltegravir once daily

Raltegravir coated tablets and Faldaprevir soft gelatin capsules

Oral with 240 mL of water Day 1: 400 mg raltegravir twice daily and 240 mg faldaprevir twice daily (loading dose) Days 2 to 5: 400 mg raltegravir twice daily and 240 mg faldaprevir once daily Day 6: 400 mg raltegravir once daily and 240 mg faldaprevir once daily

Overall Number of Participants Analyzed 24 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1300
(115%)
3220
(108%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Raltegravir, Raltegravir + Faldaprevir
Comments Ratio Raltegravir plus Faldaprevir and Raltegravir for the category Raltegravir
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability(No formal testing was performed)
Statistical Test of Hypothesis P-Value 0.9973
Comments P-value for ratio outside interval 0.8-1.25
Method ANOVA
Comments Adjusted geometric mean ratio
Method of Estimation Estimation Parameter Adjusted Geometric Mean ratio
Estimated Value 245.72
Confidence Interval 95%
168.460 to 358.404
Parameter Dispersion
Type: Standard Deviation
Value: 87.1
Estimation Comments The standard deviation is actually the geometric coefficient of variation
Time Frame Up to 23 days (+1day)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Raltegravir Raltegravir + Faldaprevir
Hide Arm/Group Description

coated tablets, oral administration with 240 ml water

Raltegravir: low dose oral administration

coated tablets and soft gelatine capsule, oral administration with 240 ml water

Raltegravir: low dose oral administration

Faldaprevir: medium dose oral administration

All-Cause Mortality
Raltegravir Raltegravir + Faldaprevir
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Raltegravir Raltegravir + Faldaprevir
Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/23 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Raltegravir Raltegravir + Faldaprevir
Affected / at Risk (%) Affected / at Risk (%)
Total   6/24 (25.00%)   13/23 (56.52%) 
Gastrointestinal disorders     
Nausea  1  1/24 (4.17%)  6/23 (26.09%) 
Diarrhoea  1  1/24 (4.17%)  3/23 (13.04%) 
Vomiting  1  0/24 (0.00%)  2/23 (8.70%) 
Flatulence  1  2/24 (8.33%)  1/23 (4.35%) 
General disorders     
Fatigue  1  0/24 (0.00%)  5/23 (21.74%) 
Nervous system disorders     
Headache  1  3/24 (12.50%)  5/23 (21.74%) 
Dizziness  1  2/24 (8.33%)  0/23 (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
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01785160     History of Changes
Other Study ID Numbers: 1220.65
2012-004872-21 ( EudraCT Number: EudraCT )
First Submitted: December 13, 2012
First Posted: February 7, 2013
Results First Submitted: July 3, 2015
Results First Posted: August 3, 2015
Last Update Posted: August 3, 2015