Potential for Drug-drug Interactions Between Boceprevir and Etravirine in HIV/Hepatitis C Virus Negative Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01427504
First received: August 24, 2011
Last updated: June 4, 2013
Last verified: June 2013
Results First Received: November 16, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Bio-equivalence Study;   Intervention Model: Crossover Assignment;   Masking: Open Label
Conditions: Hepatitis C
HIV
Intervention: Drug: boceprevir; etravirine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment occured at the University of Colorado Hospital beginning September 1, 2011 and ended on October 4, 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
There were 8 subjects that were excluded from trial before assignment to groups; 5 due to personal reasons, 2 due to elevated bilirubin, and 1 due to elevated serum creatinine.

Reporting Groups
  Description
Sequence 1a Sequence 1,2,3: boceprevir 800 mg three times daily alone, then etravirine 200 mg twice daily only, then both boceprevir 800 mg three times daily and etravirine 200 mg twice daily were each given for 11-14 days. Each intervention was followed by a 14 day washout period before the next sequence was started.
Sequence 1b Sequence 1,3,2: boceprevir 800 mg three times daily alone, then etravirine 200 mg twice daily only, then both boceprevir 800 mg three times daily and etravirine 200 mg twice daily were each given for 11-14 days. Each intervention was followed by a 14 day washout period before the next sequence was started.
Sequence 2a Sequence 2,1,3: boceprevir 800 mg three times daily alone, then etravirine 200 mg twice daily only, then both boceprevir 800 mg three times daily and etravirine 200 mg twice daily were each given for 11-14 days. Each intervention was followed by a 14 day washout period before the next sequence was started.
Sequence 2b Sequence 2,3,1: boceprevir 800 mg three times daily alone, then etravirine 200 mg twice daily only, then both boceprevir 800 mg three times daily and etravirine 200 mg twice daily were each given for 11-14 days. Each intervention was followed by a 14 day washout period before the next sequence was started.
Sequence 3a Sequence 3,1,2: boceprevir 800 mg three times daily alone, then etravirine 200 mg twice daily only, then both boceprevir 800 mg three times daily and etravirine 200 mg twice daily were each given for 11-14 days. Each intervention was followed by a 14 day washout period before the next sequence was started.
Sequence 3b Sequence 3,2,1: boceprevir 800 mg three times daily alone, then etravirine 200 mg twice daily only, then both boceprevir 800 mg three times daily and etravirine 200 mg twice daily were each given for 11-14 days. Each intervention was followed by a 14 day washout period before the next sequence was started.

Participant Flow:   Overall Study
    Sequence 1a     Sequence 1b     Sequence 2a     Sequence 2b     Sequence 3a     Sequence 3b  
STARTED     4     3     4     6     3     6  
Received Boceprevir     4     3     3     5     2     4  
Received Etravirine     4     2     4     6     2     4  
Received Combination     4     3     3     6     3     6  
COMPLETED     4     2     3     5     2     4  
NOT COMPLETED     0     1     1     1     1     2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sequence 1a Sequence 1,2,3: boceprevir only, then etravirine only, then both boceprevir and etravirine.
Sequence 1b Sequence 1,3,2: boceprevir only, then both boceprevir and etravirine, then etravirine only.
Sequence 2a Sequence 2,1,3: etravirine only, then boceprevir only, then both boceprevir and etravirine.
Sequence 2b Sequence 2,3,1: etravirine only, then both boceprevir and etravirine, then boceprevir only.
Sequence 3a Sequence 3,1,2: both boceprevir and etravirine, then boceprevir only, then etravirine only.
Sequence 3b Sequence 3,2,1: Both boceprevir and etravirine, then etravirine only, then boceprevir only.
Total Total of all reporting groups

Baseline Measures
    Sequence 1a     Sequence 1b     Sequence 2a     Sequence 2b     Sequence 3a     Sequence 3b     Total  
Number of Participants  
[units: participants]
  4     3     4     6     3     6     26  
Age  
[units: participants]
             
<=18 years     0     0     1     0     0     0     1  
Between 18 and 65 years     4     3     3     6     3     6     25  
>=65 years     0     0     0     0     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  42.7  ± 13.4     35.6  ± 8.0     33.3  ± 9.8     25.9  ± 3.8     42.7  ± 16.8     32.4  ± 9.3     34.2  ± 10.9  
Gender  
[units: participants]
             
Female     1     2     0     3     2     6     14  
Male     3     1     4     3     1     0     12  
Region of Enrollment  
[units: participants]
             
United States     4     3     4     6     3     6     26  



  Outcome Measures
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1.  Primary:   Boceprevir AUC Pharmacokinetics   [ Time Frame: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14 ]

2.  Primary:   Boceprevir Cmax Pharmacokinetics   [ Time Frame: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14 ]

3.  Primary:   Boceprevir C8 Pharmacokinetics   [ Time Frame: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14 ]

4.  Primary:   Etravirine AUC Pharmacokinetics   [ Time Frame: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14 ]

5.  Primary:   Etravirine Cmax Pharmacokinetics   [ Time Frame: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14 ]

6.  Primary:   Etravirine Cmin Pharmacokinetics   [ Time Frame: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14 ]

7.  Primary:   Boceprevir AUC Pharmacokinetics Coadministered With Etravirine   [ Time Frame: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14 ]

8.  Primary:   Boceprevir Cmax Pharmacokinetics Coadministered With Etravirine   [ Time Frame: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14 ]

9.  Primary:   Boceprevir C8 Pharmacokinetics Coadministered With Etravirine   [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14 ]

10.  Primary:   Etravirine AUC Pharmacokinetics Coadministered With Boceprevir   [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours Post-dose on day 11-14 ]

11.  Primary:   Etravirine Cmax Pharmacokinetics Coadministered With Boceprevir   [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose on day 11-14 ]
  Hide Outcome Measure 11

Measure Type Primary
Measure Title Etravirine Cmax Pharmacokinetics Coadministered With Boceprevir
Measure Description Determine etravirine Cmax when coadministered with boceprevir. [Ratio = etravirine administered with boceprevir / etravirine administered alone]
Time Frame Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose on day 11-14  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The number of participants is based on the number of subjects that completed all three sequences of medication.

Reporting Groups
  Description
Etravirine Cmax Geometric mean ratio of etravirine Cmax when coadministered with boceprevir

Measured Values
    Etravirine Cmax  
Number of Participants Analyzed  
[units: participants]
  20  
Etravirine Cmax Pharmacokinetics Coadministered With Boceprevir  
[units: Ratio]
Geometric Mean ( 90% Confidence Interval )
  0.76  
  ( 0.68 to 0.85 )  

No statistical analysis provided for Etravirine Cmax Pharmacokinetics Coadministered With Boceprevir



12.  Primary:   Etravirine Cmin Pharmacokinetics Coadministered With Boceprevir   [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose on day 11-14 ]


  Serious Adverse Events


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  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
  1. Healthy volunteer study does not take into account other medications being prescribed to treat the co-infected population.
  2. An interaction at the level of enzyme induction is difficult to rule out since we sampled etravirine over 12 hours.


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