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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hepatitis C, HIV

Intervention / Treatment
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* Drug: boceprevir; etravirine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1a<br>Sequence 1,2,3: boceprevir only, then etravirine only, then both boceprevir and etravirine. | Drug: boceprevir; etravirine<br>* boceprevir tablets 800 mg, every 8 hours x 11-14 days. etravirine tablets 200 mg, every 12 hours x 11-14 days.<br>|
| Experimental: Sequence 1b<br>Sequence 1,3,2: boceprevir only, then both boceprevir and etravirine, then etravirine only. | Drug: boceprevir; etravirine<br>* boceprevir tablets 800 mg, every 8 hours x 11-14 days. etravirine tablets 200 mg, every 12 hours x 11-14 days.<br>|
| Experimental: Sequence 2a<br>Sequence 2,1,3: etravirine only, then boceprevir only, then both boceprevir and etravirine. | Drug: boceprevir; etravirine<br>* boceprevir tablets 800 mg, every 8 hours x 11-14 days. etravirine tablets 200 mg, every 12 hours x 11-14 days.<br>|
| Experimental: Sequence 2b<br>Sequence 2,3,1: etravirine only, then both boceprevir and etravirine, then boceprevir only. | Drug: boceprevir; etravirine<br>* boceprevir tablets 800 mg, every 8 hours x 11-14 days. etravirine tablets 200 mg, every 12 hours x 11-14 days.<br>|
| Experimental: Sequence 3a<br>Sequence 3,1,2: both boceprevir and etravirine, then boceprevir only, then etravirine only. | Drug: boceprevir; etravirine<br>* boceprevir tablets 800 mg, every 8 hours x 11-14 days. etravirine tablets 200 mg, every 12 hours x 11-14 days.<br>|
| Experimental: Sequence 3b<br>Sequence 3,2,1: Both boceprevir and etravirine, then etravirine only, then boceprevir only. | Drug: boceprevir; etravirine<br>* boceprevir tablets 800 mg, every 8 hours x 11-14 days. etravirine tablets 200 mg, every 12 hours x 11-14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, HIV