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Trial record 12 of 33 for:    " July 27, 2011":" August 26, 2011"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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

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ClinicalTrials.gov Identifier: NCT01427504
Recruitment Status : Completed
First Posted : September 1, 2011
Results First Posted : July 9, 2013
Last Update Posted : July 9, 2013
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label)
Conditions Hepatitis C
HIV
Intervention Drug: boceprevir; etravirine
Enrollment 26
Recruitment Details Recruitment occured at the University of Colorado Hospital beginning September 1, 2011 and ended on October 4, 2011.
Pre-assignment Details 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.
Arm/Group Title Sequence 1a Sequence 1b Sequence 2a Sequence 2b Sequence 3a Sequence 3b
Hide Arm/Group Description 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 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 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 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 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 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.
Period Title: Overall Study
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
Arm/Group Title Sequence 1a Sequence 1b Sequence 2a Sequence 2b Sequence 3a Sequence 3b Total
Hide Arm/Group Description Sequence 1,2,3: boceprevir only, then etravirine only, then both boceprevir and etravirine. Sequence 1,3,2: boceprevir only, then both boceprevir and etravirine, then etravirine only. Sequence 2,1,3: etravirine only, then boceprevir only, then both boceprevir and etravirine. Sequence 2,3,1: etravirine only, then both boceprevir and etravirine, then boceprevir only. Sequence 3,1,2: both boceprevir and etravirine, then boceprevir only, then etravirine only. Sequence 3,2,1: Both boceprevir and etravirine, then etravirine only, then boceprevir only. Total of all reporting groups
Overall Number of Baseline Participants 4 3 4 6 3 6 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 4 participants 6 participants 3 participants 6 participants 26 participants
<=18 years
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.8%
Between 18 and 65 years
4
 100.0%
3
 100.0%
3
  75.0%
6
 100.0%
3
 100.0%
6
 100.0%
25
  96.2%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 3 participants 4 participants 6 participants 3 participants 6 participants 26 participants
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)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 4 participants 6 participants 3 participants 6 participants 26 participants
Female
1
  25.0%
2
  66.7%
0
   0.0%
3
  50.0%
2
  66.7%
6
 100.0%
14
  53.8%
Male
3
  75.0%
1
  33.3%
4
 100.0%
3
  50.0%
1
  33.3%
0
   0.0%
12
  46.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 3 participants 4 participants 6 participants 3 participants 6 participants 26 participants
4 3 4 6 3 6 26
1.Primary Outcome
Title Boceprevir AUC Pharmacokinetics
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants was based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Boceprevir AUC
Hide Arm/Group Description:
Geometric mean of boceprevir AUC administered alone.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
4601
(47%)
2.Primary Outcome
Title Boceprevir Cmax Pharmacokinetics
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Boceprevir Cmax
Hide Arm/Group Description:
Geometric mean of boceprevir Cmax when administered alone.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1423
(0.66% to 0.91%)
3.Primary Outcome
Title Boceprevir C8 Pharmacokinetics
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Boceprevir C8
Hide Arm/Group Description:
Geometric mean of boceprevir Cmax when administered alone.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
106
(64%)
4.Primary Outcome
Title Etravirine AUC Pharmacokinetics
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Etravirine AUC
Hide Arm/Group Description:
Geometric mean of etravirine AUC when administered alone.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
7698
(33%)
5.Primary Outcome
Title Etravirine Cmax Pharmacokinetics
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Etravirine Cmax
Hide Arm/Group Description:
Geometric mean of etravirine Cmax when administered alone.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
900
(29%)
6.Primary Outcome
Title Etravirine Cmin Pharmacokinetics
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Etravirine Cmin
Hide Arm/Group Description:
Geometric mean of etravirine Cmin when administered alone.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
439
(46%)
7.Primary Outcome
Title Boceprevir AUC Pharmacokinetics Coadministered With Etravirine
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Boceprevir AUC Coadministered With Etravirine
Hide Arm/Group Description:
Geometric mean ratio of boceprevir AUC when coadministered with etravirine
Overall Number of Participants Analyzed 20
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
1.10
(0.94 to 1.28)
8.Primary Outcome
Title Boceprevir Cmax Pharmacokinetics Coadministered With Etravirine
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Boceprevir Cmax Coadministered With Etravirine
Hide Arm/Group Description:
Geometric mean ratio of boceprevir Cmax when coadministered with etravirine
Overall Number of Participants Analyzed 20
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
1.10
(0.94 to 1.29)
9.Primary Outcome
Title Boceprevir C8 Pharmacokinetics Coadministered With Etravirine
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Boceprevir C8 Coadministered With Etravirine
Hide Arm/Group Description:
Geometric mean ratio of boceprevir C8 when coadministered with etravirine
Overall Number of Participants Analyzed 20
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
0.88
(0.66 to 1.17)
10.Primary Outcome
Title Etravirine AUC Pharmacokinetics Coadministered With Boceprevir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Etravirine AUC Coadministered With Boceprevir
Hide Arm/Group Description:
Geometric mean ratio of etravirine AUC when coadministered with boceprevir
Overall Number of Participants Analyzed 20
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
0.77
(0.66 to 0.91)
11.Primary Outcome
Title Etravirine Cmax Pharmacokinetics Coadministered With Boceprevir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Etravirine Cmax
Hide Arm/Group Description:
Geometric mean ratio of etravirine Cmax when coadministered with boceprevir
Overall Number of Participants Analyzed 20
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
0.76
(0.68 to 0.85)
12.Primary Outcome
Title Etravirine Cmin Pharmacokinetics Coadministered With Boceprevir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of participants is based on the number of subjects that completed all three sequences of medication.
Arm/Group Title Etravirine Cmin Coadministered With Boceprevir
Hide Arm/Group Description:
Geometric mean ratio of etravirine Cmin when coadministered with boceprevir
Overall Number of Participants Analyzed 20
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
0.71
(0.54 to 0.95)
Time Frame 4 months
Adverse Event Reporting 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.
 
Arm/Group Title Boceprevir Alone Etravirine Alone Boceprevir Coadministered With Etravirine
Hide Arm/Group Description Subjects took boceprevir alone, 800 mg thrice daily, for 10-14 days. Subjects took etravirine alone, 200 mg twice daily, for 10-14 days Boceprevir, 800 mg thrice daily, coadministered with etravirine, 200 mg twice daily for 10-14 days.
All-Cause Mortality
Boceprevir Alone Etravirine Alone Boceprevir Coadministered With Etravirine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Boceprevir Alone Etravirine Alone Boceprevir Coadministered With Etravirine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/21 (0.00%)      1/22 (4.55%)      5/25 (20.00%)    
Gastrointestinal disorders       
Presumed Viral Illness  2  0/21 (0.00%)  0 0/22 (0.00%)  0 1/25 (4.00%)  1
Nervous system disorders       
Increased energy, anxiety, nervousness, insomnia  2  0/21 (0.00%)  0 0/22 (0.00%)  0 1/25 (4.00%)  1
Skin and subcutaneous tissue disorders       
Rash  1  0/21 (0.00%)  0 1/22 (4.55%)  1 3/25 (12.00%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, Grade 2
2
Term from vocabulary, Serious, Mild/Mod
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Boceprevir Alone Etravirine Alone Boceprevir Coadministered With Etravirine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/21 (90.48%)      11/22 (50.00%)      21/25 (84.00%)    
Gastrointestinal disorders       
Altered Taste  1  18/21 (85.71%)  18 0/22 (0.00%)  0 16/25 (64.00%)  16
Nausea  1  4/21 (19.05%)  4 3/22 (13.64%)  3 3/25 (12.00%)  3
General disorders       
Headache  1  4/21 (19.05%)  4 5/22 (22.73%)  5 4/25 (16.00%)  4
Fatigue  1  3/21 (14.29%)  3 1/22 (4.55%)  1 3/25 (12.00%)  3
Hypokalemia  1  4/21 (19.05%)  4 0/22 (0.00%)  0 2/25 (8.00%)  2
Skin and subcutaneous tissue disorders       
Rash  1  0/21 (0.00%)  0 2/22 (9.09%)  2 4/25 (16.00%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, Serious, Mild/Mod
  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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Dr. Jennifer Kiser
Organization: University of Colorado
Phone: 303-724-6131
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01427504     History of Changes
Other Study ID Numbers: 11-1046
First Submitted: August 24, 2011
First Posted: September 1, 2011
Results First Submitted: November 16, 2012
Results First Posted: July 9, 2013
Last Update Posted: July 9, 2013