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

NCT01427504 | Completed Results

• 1 other identifier: 11-1046
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C; HIV

Keywords

HCV; HIV

Outcome Measures

Primary Outcomes (12)

• 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

Study Arms (6)

Sequence 1a

EXPERIMENTAL

Sequence 1,2,3: boceprevir only, then etravirine only, then both boceprevir and etravirine.

Drug: boceprevir; etravirine

Sequence 1b

EXPERIMENTAL

Sequence 1,3,2: boceprevir only, then both boceprevir and etravirine, then etravirine only.

Drug: boceprevir; etravirine

Sequence 2a

EXPERIMENTAL

Sequence 2,1,3: etravirine only, then boceprevir only, then both boceprevir and etravirine.

Drug: boceprevir; etravirine

Sequence 2b

EXPERIMENTAL

Sequence 2,3,1: etravirine only, then both boceprevir and etravirine, then boceprevir only.

Drug: boceprevir; etravirine

Sequence 3a

EXPERIMENTAL

Sequence 3,1,2: both boceprevir and etravirine, then boceprevir only, then etravirine only.

Drug: boceprevir; etravirine

Sequence 3b

EXPERIMENTAL

Sequence 3,2,1: Both boceprevir and etravirine, then etravirine only, then boceprevir only.

Drug: boceprevir; etravirine

Interventions

boceprevir; etravirine DRUG

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

Sequence 1a; Sequence 1b; Sequence 2a; Sequence 2b; Sequence 3a; Sequence 3b

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; etravirine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Jennifer Kiser
• Organization: University of Colorado

jennifer.kiser@ucdenver.edu

303-724-6131

Study Officials

• Jennifer Kiser, PharmD

  Univesity of Colorado Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2011
• First Posted: September 1, 2011
• Study Start: August 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: March 1, 2012
• Last Updated: July 9, 2013
• Results First Posted: July 9, 2013

Record last verified: 2013-06

Locations

US (1)