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 ]

Measure Type Primary
Measure Title Boceprevir AUC Pharmacokinetics
Measure Description Determine boceprevir area-under-the concentration time curve (AUC) when administered alone.
Time Frame Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 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 was based on the number of subjects that completed all three sequences of medication.

Reporting Groups
  Description
Boceprevir AUC Geometric mean of boceprevir AUC administered alone.

Measured Values
    Boceprevir AUC  
Number of Participants Analyzed  
[units: participants]
  20  
Boceprevir AUC Pharmacokinetics  
[units: ng*hr/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  4601  
  ( 47% )  

No statistical analysis provided for Boceprevir AUC Pharmacokinetics



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 ]

Measure Type Primary
Measure Title Boceprevir Cmax Pharmacokinetics
Measure Description Determine the Cmax of boceprevir when administered alone.
Time Frame Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 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
Boceprevir Cmax Geometric mean of boceprevir Cmax when administered alone.

Measured Values
    Boceprevir Cmax  
Number of Participants Analyzed  
[units: participants]
  20  
Boceprevir Cmax Pharmacokinetics  
[units: ng/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  1423  
  ( 0.66% to 0.91% )  

No statistical analysis provided for Boceprevir Cmax Pharmacokinetics



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 ]

Measure Type Primary
Measure Title Boceprevir C8 Pharmacokinetics
Measure Description Determine boceprevir 8 hour concentration when administered alone.
Time Frame Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 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
Boceprevir C8 Geometric mean of boceprevir Cmax when administered alone.

Measured Values
    Boceprevir C8  
Number of Participants Analyzed  
[units: participants]
  20  
Boceprevir C8 Pharmacokinetics  
[units: ng/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  106  
  ( 64% )  

No statistical analysis provided for Boceprevir C8 Pharmacokinetics



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 ]

Measure Type Primary
Measure Title Etravirine AUC Pharmacokinetics
Measure Description Determine etravirine area under the concentration vs. time curve (AUC)when administered alone.
Time Frame Pre-dose and, 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 AUC Geometric mean of etravirine AUC when administered alone.

Measured Values
    Etravirine AUC  
Number of Participants Analyzed  
[units: participants]
  20  
Etravirine AUC Pharmacokinetics  
[units: ng*hr/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  7698  
  ( 33% )  

No statistical analysis provided for Etravirine AUC Pharmacokinetics



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 ]

Measure Type Primary
Measure Title Etravirine Cmax Pharmacokinetics
Measure Description Determine etravirine Cmax when administered alone
Time Frame Pre-dose and, 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 of etravirine Cmax when administered alone.

Measured Values
    Etravirine Cmax  
Number of Participants Analyzed  
[units: participants]
  20  
Etravirine Cmax Pharmacokinetics  
[units: ng/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  900  
  ( 29% )  

No statistical analysis provided for Etravirine Cmax Pharmacokinetics



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 ]

Measure Type Primary
Measure Title Etravirine Cmin Pharmacokinetics
Measure Description Determine etravirine Cmin when administered alone
Time Frame Pre-dose and, 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 Cmin Geometric mean of etravirine Cmin when administered alone.

Measured Values
    Etravirine Cmin  
Number of Participants Analyzed  
[units: participants]
  20  
Etravirine Cmin Pharmacokinetics  
[units: ng/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  439  
  ( 46% )  

No statistical analysis provided for Etravirine Cmin Pharmacokinetics



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 ]

Measure Type Primary
Measure Title Boceprevir AUC Pharmacokinetics Coadministered With Etravirine
Measure Description Determine boceprevir AUC when coadministered with etravirine. [Ratio = boceprevir administered with etravirine/ boceprevir alone]
Time Frame Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 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
Boceprevir AUC Coadministered With Etravirine Geometric mean ratio of boceprevir AUC when coadministered with etravirine

Measured Values
    Boceprevir AUC Coadministered With Etravirine  
Number of Participants Analyzed  
[units: participants]
  20  
Boceprevir AUC Pharmacokinetics Coadministered With Etravirine  
[units: Ratio]
Geometric Mean ( 90% Confidence Interval )
  1.10  
  ( 0.94 to 1.28 )  

No statistical analysis provided for Boceprevir AUC Pharmacokinetics Coadministered With Etravirine



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 ]

Measure Type Primary
Measure Title Boceprevir Cmax Pharmacokinetics Coadministered With Etravirine
Measure Description Determine boceprevir Cmax when coadministered with etravirine. [Ratio = boceprevir administered with etravirine / boceprevir alone]
Time Frame Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 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
Boceprevir Cmax Coadministered With Etravirine Geometric mean ratio of boceprevir Cmax when coadministered with etravirine

Measured Values
    Boceprevir Cmax Coadministered With Etravirine  
Number of Participants Analyzed  
[units: participants]
  20  
Boceprevir Cmax Pharmacokinetics Coadministered With Etravirine  
[units: Ratio]
Geometric Mean ( 90% Confidence Interval )
  1.10  
  ( 0.94 to 1.29 )  

No statistical analysis provided for Boceprevir Cmax Pharmacokinetics Coadministered With Etravirine



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 ]

Measure Type Primary
Measure Title Boceprevir C8 Pharmacokinetics Coadministered With Etravirine
Measure Description Determine boceprevir 8 hour concentration when coadministered with etravirine. [Ratio = boceprevir administered with etravirine / boceprevir administered alone]
Time Frame Pre-dose, 1, 2, 3, 4, 5, 6, and 8 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
Boceprevir C8 Coadministered With Etravirine Geometric mean ratio of boceprevir C8 when coadministered with etravirine

Measured Values
    Boceprevir C8 Coadministered With Etravirine  
Number of Participants Analyzed  
[units: participants]
  20  
Boceprevir C8 Pharmacokinetics Coadministered With Etravirine  
[units: Ratio]
Geometric Mean ( 90% Confidence Interval )
  0.88  
  ( 0.66 to 1.17 )  

No statistical analysis provided for Boceprevir C8 Pharmacokinetics Coadministered With Etravirine



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 ]

Measure Type Primary
Measure Title Etravirine AUC Pharmacokinetics Coadministered With Boceprevir
Measure Description Determine etravirine AUC when coadministered with boceprevir. [Ratio = Etravirine administered with bocepreivr / 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 AUC Coadministered With Boceprevir Geometric mean ratio of etravirine AUC when coadministered with boceprevir

Measured Values
    Etravirine AUC Coadministered With Boceprevir  
Number of Participants Analyzed  
[units: participants]
  20  
Etravirine AUC Pharmacokinetics Coadministered With Boceprevir  
[units: Ratio]
Geometric Mean ( 90% Confidence Interval )
  0.77  
  ( 0.66 to 0.91 )  

No statistical analysis provided for Etravirine AUC Pharmacokinetics Coadministered With Boceprevir



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 ]

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 ]

Measure Type Primary
Measure Title Etravirine Cmin Pharmacokinetics Coadministered With Boceprevir
Measure Description Determine etravirine Cmin 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 Cmin Coadministered With Boceprevir Geometric mean ratio of etravirine Cmin when coadministered with boceprevir

Measured Values
    Etravirine Cmin Coadministered With Boceprevir  
Number of Participants Analyzed  
[units: participants]
  20  
Etravirine Cmin Pharmacokinetics Coadministered With Boceprevir  
[units: Ratio]
Geometric Mean ( 90% Confidence Interval )
  0.71  
  ( 0.54 to 0.95 )  

No statistical analysis provided for Etravirine Cmin Pharmacokinetics Coadministered With Boceprevir




  Serious Adverse Events


  Other Adverse Events


  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.


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