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

A Bioequivalence Study to Evaluate the Potential for Drug-drug Interactions Between Boceprevir 800mg Thrice Daily and the HIV Non-nucleoside Reverse Transcriptase Inhibitor Etravirine 200mg Twice Daily in HIV/(Hepatitis C Virus) (HCV) Negative Volunteers

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01427504

Enrollment

Registered

2011-09-01

Start date

2011-08-31

Completion date

2012-03-31

Last updated

2013-07-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C, HIV

Keywords

HCV, HIV

Brief summary

The investigators believe that boceprevir's drug concentrations will be reduced when administered in combination with etravirine. The investigators believe that etravirine's drug concentrations will be increased when administered in combination with boceprevir. Additionally, the investigators believe that boceprevir and etravirine are safe when administered alone or in combination.

Detailed description

To investigate the potential for drug interactions between boceprevir and etravirine, participants will receive each drug alone and the drugs in combination for 11-14 days. The pharmacokinetics of boceprevir and etravirine when given in combination vs. alone will be compared.

Interventions

DRUGboceprevir; etravirine

boceprevir tablets 800 mg, every 8 hours x 11-14 days. etravirine tablets 200 mg, every 12 hours x 11-14 days.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

* Men and women ages 18-60 years * Absence of HIV-1 and HCV antibodies at screening * Ability and willingness to give written informed consent before the first trial-related activity

Exclusion criteria

* Pregnancy * Breastfeeding * Active alcohol or drug abuse that, in the opinion of the investigators, would interfere with adherence to study requirements. * Participation in any investigation drug study within 30 days prior to study. * Currently active or chronic gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease or malignancy requiring pharmacologic treatment, and/or if in the opinion of the investigator, would affect study participation, safety, or integrity of results. * Use of concomitant medication, including investigational, prescription, and over-the-counter products and dietary supplements with the following exceptions:aspirin, acetaminophen, once daily multivitamins, mineral supplements and hormonal oral contraceptives (other than those that contain drospirenone). Concomitant medications other than those listed above must have been discontinued at least 14 days before study entry. * Currently active dermatitis or urticaria or diagnosis of eczema or psoriasis. * History of significant drug allergy (i.e., anaphylaxis and/or angioedema) * Subjects with the following laboratory abnormalities at screening as defined by the 2004 Division of AIDS Table for grading the Severity of Adult and Pediatric Adverse Events and in accordance with the normal ranges of the trial clinical laboratory: serum creatinine grade 1 or greater (\>1.1 x upper limit of laboratory normal range (ULN); hemoglobin grade 1 or greater (≤ 10.9 g/dL); platelet count grade 1 or greater (≤ 124.999 x 109/L); absolute neutrophil count grade 1 or greater (≤ 1.3 x 109/L); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (≥ 1.25 x ULN); total bilirubin grade 1 or greater (≥ 1.1 x ULN), any other laboratory abnormality of grade 2 or above

Design outcomes

Primary

Measure	Time frame	Description
Boceprevir AUC Pharmacokinetics	Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14	Determine boceprevir area-under-the concentration time curve (AUC) when administered alone.
Boceprevir Cmax Pharmacokinetics	Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14	Determine the Cmax of boceprevir when administered alone.
Boceprevir C8 Pharmacokinetics	Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14	Determine boceprevir 8 hour concentration when administered alone.
Etravirine AUC Pharmacokinetics	Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14	Determine etravirine area under the concentration vs. time curve (AUC)when administered alone.
Etravirine Cmax Pharmacokinetics	Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14	Determine etravirine Cmax when administered alone
Etravirine Cmin Pharmacokinetics	Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours post dose on day 11-14	Determine etravirine Cmin when administered alone
Boceprevir AUC Pharmacokinetics Coadministered With Etravirine	Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14	Determine boceprevir AUC when coadministered with etravirine. \[Ratio = boceprevir administered with etravirine/ boceprevir alone\]
Boceprevir Cmax Pharmacokinetics Coadministered With Etravirine	Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14	Determine boceprevir Cmax when coadministered with etravirine. \[Ratio = boceprevir administered with etravirine / boceprevir alone\]
Boceprevir C8 Pharmacokinetics Coadministered With Etravirine	Pre-dose, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14	Determine boceprevir 8 hour concentration when coadministered with etravirine. \[Ratio = boceprevir administered with etravirine / boceprevir administered alone\]
Etravirine AUC Pharmacokinetics Coadministered With Boceprevir	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours Post-dose on day 11-14	Determine etravirine AUC when coadministered with boceprevir. \[Ratio = Etravirine administered with bocepreivr / etravirine administered alone\]
Etravirine Cmax Pharmacokinetics Coadministered With Boceprevir	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose on day 11-14	Determine etravirine Cmax when coadministered with boceprevir. \[Ratio = etravirine administered with boceprevir / etravirine administered alone\]
Etravirine Cmin Pharmacokinetics Coadministered With Boceprevir	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose on day 11-14	Determine etravirine Cmin when coadministered with boceprevir. \[Ratio = etravirine administered with boceprevir / etravirine administered alone\]

Countries

United States

Participant flow

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.

Participants by arm

Arm	Count
Sequence 1a Sequence 1,2,3: boceprevir only, then etravirine only, then both boceprevir and etravirine.	4
Sequence 1b Sequence 1,3,2: boceprevir only, then both boceprevir and etravirine, then etravirine only.	3
Sequence 2a Sequence 2,1,3: etravirine only, then boceprevir only, then both boceprevir and etravirine.	4
Sequence 2b Sequence 2,3,1: etravirine only, then both boceprevir and etravirine, then boceprevir only.	6
Sequence 3a Sequence 3,1,2: both boceprevir and etravirine, then boceprevir only, then etravirine only.	3
Sequence 3b Sequence 3,2,1: Both boceprevir and etravirine, then etravirine only, then boceprevir only.	6
Total	26

Baseline characteristics

Characteristic	Sequence 1b	Sequence 2a	Sequence 2b	Sequence 1a	Sequence 3a	Sequence 3b	Total
Age, Categorical <=18 years	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	3 Participants	3 Participants	6 Participants	4 Participants	3 Participants	6 Participants	25 Participants
Age Continuous	35.6 years STANDARD_DEVIATION 8	33.3 years STANDARD_DEVIATION 9.8	25.9 years STANDARD_DEVIATION 3.8	42.7 years STANDARD_DEVIATION 13.4	42.7 years STANDARD_DEVIATION 16.8	32.4 years STANDARD_DEVIATION 9.3	34.2 years STANDARD_DEVIATION 10.9
Region of Enrollment United States	3 participants	4 participants	6 participants	4 participants	3 participants	6 participants	26 participants
Sex: Female, Male Female	2 Participants	0 Participants	3 Participants	1 Participants	2 Participants	6 Participants	14 Participants
Sex: Female, Male Male	1 Participants	4 Participants	3 Participants	3 Participants	1 Participants	0 Participants	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	19 / 21	11 / 22	21 / 25
serious Total, serious adverse events	0 / 21	1 / 22	5 / 25

Outcome results

Primary

Boceprevir AUC Pharmacokinetics

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

Population: The number of participants was based on the number of subjects that completed all three sequences of medication.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Boceprevir AUC	Boceprevir AUC Pharmacokinetics	4601 ng*hr/mL	Geometric Coefficient of Variation 47

Primary

Boceprevir AUC Pharmacokinetics Coadministered With Etravirine

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