Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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
  Hide Participant Flow

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
  Hide Baseline Characteristics

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
  Show All Outcome Measures

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 ]

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


  Other Adverse Events
  Hide Other Adverse Events

Time Frame 4 months
Additional Description Adverse events were verbally assessed by study investigators. Laboratory tests were performed at baseline and at all three intensive pharmacokinetic study visits. Clinical and laboratory adverse events were graded using the 2004 Division of AIDS table for grading the severity of adult and pediatric adverse experiences.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Boceprevir Alone Subjects took boceprevir alone, 800 mg thrice daily, for 10-14 days.
Etravirine Alone Subjects took etravirine alone, 200 mg twice daily, for 10-14 days
Boceprevir Coadministered With Etravirine Boceprevir, 800 mg thrice daily, coadministered with etravirine, 200 mg twice daily for 10-14 days.

Other Adverse Events
    Boceprevir Alone     Etravirine Alone     Boceprevir Coadministered With Etravirine  
Total, other (not including serious) adverse events        
# participants affected / at risk     19/21     11/22     21/25  
Gastrointestinal disorders        
Altered Taste † 1      
# participants affected / at risk     18/21 (85.71%)     0/22 (0.00%)     16/25 (64.00%)  
# events     18     0     16  
Nausea † 1      
# participants affected / at risk     4/21 (19.05%)     3/22 (13.64%)     3/25 (12.00%)  
# events     4     3     3  
General disorders        
Headache † 1      
# participants affected / at risk     4/21 (19.05%)     5/22 (22.73%)     4/25 (16.00%)  
# events     4     5     4  
Fatigue † 1      
# participants affected / at risk     3/21 (14.29%)     1/22 (4.55%)     3/25 (12.00%)  
# events     3     1     3  
Hypokalemia † 1      
# participants affected / at risk     4/21 (19.05%)     0/22 (0.00%)     2/25 (8.00%)  
# events     4     0     2  
Skin and subcutaneous tissue disorders        
Rash † 1      
# participants affected / at risk     0/21 (0.00%)     2/22 (9.09%)     4/25 (16.00%)  
# events     0     2     4  
Events were collected by systematic assessment
1 Term from vocabulary, Serious, Mild/Mod



  Limitations and Caveats
  Hide Limitations and Caveats

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.


  More Information