Trial Outcomes & Findings for Potential for Drug-drug Interactions Between Boceprevir and Etravirine in HIV/Hepatitis C Virus Negative Volunteers (NCT NCT01427504)
NCT ID: NCT01427504
Last Updated: 2013-07-09
Results Overview
Determine boceprevir area-under-the concentration time curve (AUC) when administered alone.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
26 participants
Primary outcome timeframe
Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14
Results posted on
2013-07-09
Participant Flow
Recruitment occured at the University of Colorado Hospital beginning September 1, 2011 and ended on October 4, 2011.
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.
Participant milestones
| Measure |
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.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
4
|
6
|
3
|
6
|
|
Overall Study
Received Boceprevir
|
4
|
3
|
3
|
5
|
2
|
4
|
|
Overall Study
Received Etravirine
|
4
|
2
|
4
|
6
|
2
|
4
|
|
Overall Study
Received Combination
|
4
|
3
|
3
|
6
|
3
|
6
|
|
Overall Study
COMPLETED
|
4
|
2
|
3
|
5
|
2
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
1
|
1
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Potential for Drug-drug Interactions Between Boceprevir and Etravirine in HIV/Hepatitis C Virus Negative Volunteers
Baseline characteristics by cohort
| Measure |
Sequence 1a
n=4 Participants
Sequence 1,2,3: boceprevir only, then etravirine only, then both boceprevir and etravirine.
|
Sequence 1b
n=3 Participants
Sequence 1,3,2: boceprevir only, then both boceprevir and etravirine, then etravirine only.
|
Sequence 2a
n=4 Participants
Sequence 2,1,3: etravirine only, then boceprevir only, then both boceprevir and etravirine.
|
Sequence 2b
n=6 Participants
Sequence 2,3,1: etravirine only, then both boceprevir and etravirine, then boceprevir only.
|
Sequence 3a
n=3 Participants
Sequence 3,1,2: both boceprevir and etravirine, then boceprevir only, then etravirine only.
|
Sequence 3b
n=6 Participants
Sequence 3,2,1: Both boceprevir and etravirine, then etravirine only, then boceprevir only.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
25 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age Continuous
|
42.7 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
35.6 years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
33.3 years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
25.9 years
STANDARD_DEVIATION 3.8 • n=4 Participants
|
42.7 years
STANDARD_DEVIATION 16.8 • n=21 Participants
|
32.4 years
STANDARD_DEVIATION 9.3 • n=8 Participants
|
34.2 years
STANDARD_DEVIATION 10.9 • n=8 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
14 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
6 participants
n=4 Participants
|
3 participants
n=21 Participants
|
6 participants
n=8 Participants
|
26 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14Population: The number of participants was based on the number of subjects that completed all three sequences of medication.
Determine boceprevir area-under-the concentration time curve (AUC) when administered alone.
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Boceprevir AUC Pharmacokinetics
|
4601 ng*hr/mL
Geometric Coefficient of Variation 47
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine the Cmax of boceprevir when administered alone.
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Boceprevir Cmax Pharmacokinetics
|
1423 ng/mL
Geometric Coefficient of Variation 43 • Interval 0.66 to 0.91
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine boceprevir 8 hour concentration when administered alone.
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Boceprevir C8 Pharmacokinetics
|
106 ng/mL
Geometric Coefficient of Variation 64
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine etravirine area under the concentration vs. time curve (AUC)when administered alone.
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Etravirine AUC Pharmacokinetics
|
7698 ng*hr/mL
Geometric Coefficient of Variation 33
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine etravirine Cmax when administered alone
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Etravirine Cmax Pharmacokinetics
|
900 ng/mL
Geometric Coefficient of Variation 29
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine etravirine Cmin when administered alone
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Etravirine Cmin Pharmacokinetics
|
439 ng/mL
Geometric Coefficient of Variation 46
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine boceprevir AUC when coadministered with etravirine. \[Ratio = boceprevir administered with etravirine/ boceprevir alone\]
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Boceprevir AUC Pharmacokinetics Coadministered With Etravirine
|
1.10 Ratio
Interval 0.94 to 1.28
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine boceprevir Cmax when coadministered with etravirine. \[Ratio = boceprevir administered with etravirine / boceprevir alone\]
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Boceprevir Cmax Pharmacokinetics Coadministered With Etravirine
|
1.10 Ratio
Interval 0.94 to 1.29
|
PRIMARY outcome
Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine boceprevir 8 hour concentration when coadministered with etravirine. \[Ratio = boceprevir administered with etravirine / boceprevir administered alone\]
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Boceprevir C8 Pharmacokinetics Coadministered With Etravirine
|
0.88 Ratio
Interval 0.66 to 1.17
|
PRIMARY outcome
Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours Post-dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine etravirine AUC when coadministered with boceprevir. \[Ratio = Etravirine administered with bocepreivr / etravirine administered alone\]
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Etravirine AUC Pharmacokinetics Coadministered With Boceprevir
|
0.77 Ratio
Interval 0.66 to 0.91
|
PRIMARY outcome
Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine etravirine Cmax when coadministered with boceprevir. \[Ratio = etravirine administered with boceprevir / etravirine administered alone\]
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Etravirine Cmax Pharmacokinetics Coadministered With Boceprevir
|
0.76 Ratio
Interval 0.68 to 0.85
|
PRIMARY outcome
Timeframe: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose on day 11-14Population: The number of participants is based on the number of subjects that completed all three sequences of medication.
Determine etravirine Cmin when coadministered with boceprevir. \[Ratio = etravirine administered with boceprevir / etravirine administered alone\]
Outcome measures
| Measure |
Boceprevir AUC
n=20 Participants
Geometric mean of boceprevir AUC administered alone.
|
|---|---|
|
Etravirine Cmin Pharmacokinetics Coadministered With Boceprevir
|
0.71 Ratio
Interval 0.54 to 0.95
|
Adverse Events
Boceprevir Alone
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
Etravirine Alone
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Boceprevir Coadministered With Etravirine
Serious events: 5 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Boceprevir Alone
n=21 participants at risk
Subjects took boceprevir alone, 800 mg thrice daily, for 10-14 days.
|
Etravirine Alone
n=22 participants at risk
Subjects took etravirine alone, 200 mg twice daily, for 10-14 days
|
Boceprevir Coadministered With Etravirine
n=25 participants at risk
Boceprevir, 800 mg thrice daily, coadministered with etravirine, 200 mg twice daily for 10-14 days.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/21 • 4 months
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.
|
4.5%
1/22 • Number of events 1 • 4 months
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.
|
12.0%
3/25 • Number of events 3 • 4 months
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.
|
|
Nervous system disorders
Increased energy, anxiety, nervousness, insomnia
|
0.00%
0/21 • 4 months
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.
|
0.00%
0/22 • 4 months
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.
|
4.0%
1/25 • Number of events 1 • 4 months
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.
|
|
Gastrointestinal disorders
Presumed Viral Illness
|
0.00%
0/21 • 4 months
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.
|
0.00%
0/22 • 4 months
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.
|
4.0%
1/25 • Number of events 1 • 4 months
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.
|
Other adverse events
| Measure |
Boceprevir Alone
n=21 participants at risk
Subjects took boceprevir alone, 800 mg thrice daily, for 10-14 days.
|
Etravirine Alone
n=22 participants at risk
Subjects took etravirine alone, 200 mg twice daily, for 10-14 days
|
Boceprevir Coadministered With Etravirine
n=25 participants at risk
Boceprevir, 800 mg thrice daily, coadministered with etravirine, 200 mg twice daily for 10-14 days.
|
|---|---|---|---|
|
Gastrointestinal disorders
Altered Taste
|
85.7%
18/21 • Number of events 18 • 4 months
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.
|
0.00%
0/22 • 4 months
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.
|
64.0%
16/25 • Number of events 16 • 4 months
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.
|
|
General disorders
Headache
|
19.0%
4/21 • Number of events 4 • 4 months
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.
|
22.7%
5/22 • Number of events 5 • 4 months
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.
|
16.0%
4/25 • Number of events 4 • 4 months
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.
|
|
General disorders
Fatigue
|
14.3%
3/21 • Number of events 3 • 4 months
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.
|
4.5%
1/22 • Number of events 1 • 4 months
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.
|
12.0%
3/25 • Number of events 3 • 4 months
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.
|
|
Gastrointestinal disorders
Nausea
|
19.0%
4/21 • Number of events 4 • 4 months
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.
|
13.6%
3/22 • Number of events 3 • 4 months
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.
|
12.0%
3/25 • Number of events 3 • 4 months
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.
|
|
General disorders
Hypokalemia
|
19.0%
4/21 • Number of events 4 • 4 months
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.
|
0.00%
0/22 • 4 months
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.
|
8.0%
2/25 • Number of events 2 • 4 months
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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/21 • 4 months
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.
|
9.1%
2/22 • Number of events 2 • 4 months
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.
|
16.0%
4/25 • Number of events 4 • 4 months
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place