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

Purpose

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.

Condition	Intervention
Hepatitis C HIV	Drug: boceprevir; etravirine


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-equivalence Study Intervention Model: Crossover Assignment Masking: Open Label
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions HIV/AIDS Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Etravirine Boceprevir

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:

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


Enrollment:	26
Study Start Date:	August 2011
Study Completion Date:	March 2012
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility


Ages Eligible for Study:	18 Years to 60 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01427504

Locations


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

Sponsors and Collaborators

University of Colorado, Denver

Investigators


Principal Investigator:	Jennifer Kiser, PharmD	Univesity of Colorado Denver

More Information


Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT01427504 History of Changes
Other Study ID Numbers:	11-1046
Study First Received:	August 24, 2011
Results First Received:	November 16, 2012
Last Updated:	June 4, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:


HCV HIV

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis C Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections	Flaviviridae Infections Reverse Transcriptase Inhibitors Etravirine Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents

ClinicalTrials.gov processed this record on September 29, 2016