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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C; HIV
• Intervention / Treatment: Drug: boceprevir; etravirine

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Jennifer Kiser, PharmD, Univesity of Colorado Denver

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: August 24, 2011
• First Submitted That Met QC Criteria: August 31, 2011
• First Posted (Estimate): September 1, 2011

Study Record Updates

• Last Update Posted (Estimate): July 9, 2013
• Last Update Submitted That Met QC Criteria: June 4, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: HIV; HCV
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Etravirine
• Other Study ID Numbers: 11-1046