Polymorphic Effects of Cytochrome P450 3A5 on Pharmacokinetics of Maraviroc and Its Metabolites

The purpose of this study is to evaluate the influence of genetic polymorphism of cytochrome P450 3A5 on pharmacokinetics of maraviroc and its oxidative metabolites

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Cytochrome P450 CYP3A5 Enzyme Polymorphism; Pharmacokinetics of Maraviroc
• Intervention / Treatment: Drug: Maraviroc

Detailed Description

This study aims to evaluate the effects of CYP3A5 genotype on pharmacokinetics of maraviroc and its oxidative metabolites. A single oral dose of 300 mg maraviroc will be given to 24 eligible healthy individuals who will be screened and determined to have specific CYP3A5 genotype - 8 homozygous wild type (2 CYP3A5*1 alleles), 8 heterozygous (1 CYP3A5*1 allele and 1 mutant allele), and 8 without wild type genotype (2 mutant alleles). Blood samples will be drawn and urine samples will be collected immediately before and during a 32-hr period following the dose. The concentrations of maraviroc and its oxidative metabolites from the blood and urine samples will be measured and the pharmacokinetics of maraviroc and its metabolites will be compared among the three groups with different CYP3A5 polymorphic status.

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• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21210
      • The Johns Hopkins University School of Medicine Division of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy with no acute medical illness
• Willing to provide written informed consent
• Age 18-65 years
• Negative serum pregnancy test (females only) at screening and a negative urine pregnancy test (females only) on day of dosing
• HIV seronegative at screening, as determined by any licensed ELISA
• At screening, no evidence of hepatic or renal impairment (LFT's < 1.5 Upper Limit of Normal (ULN), creatinine clearance > than 60 ml/min, total bilirubin below ULN, AST and ALT below 1.5 ULN)
• 8 subjects with homozygous CYP3A5 allele *1 (wild type)
• 8 subjects with 1 CYP3A5*1 allele and 1 mutant allele
• 8 subjects with CYP3A5 allele other than *1

Exclusion Criteria:

• Concomitant medication (prescription or over-the-counter) or herbal supplements for which there is a known risk of pharmacokinetic or pharmacodynamic drug interactions, including those that inhibit CYP3A4 as listed on the P450 Drug Interaction Table (http://medicine.iupui.edu/clinpharm/ddis/table.aspx)
• History of postural hypotension or cardiovascular disease
• Active medical or psychological condition that, in the opinion of the investigator, might put the volunteer at undue risk or interfere with the participation of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Maraviroc; single oral administration of 300 mg maraviroc	Drug: Maraviroc; Other Names: Selzentry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration-time curve	0-32 hour post dose administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Clearance	0-32 hr post dose administration
Plasma peak concentration	0-32 hr post dose administration
Plasma half-life	0-32 hr post dose administration
Urinary metabolic ratio	0-32 hr post dose administration

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Namandje N Bumpus, Ph.D, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: November 4, 2013
• First Submitted That Met QC Criteria: November 4, 2013
• First Posted (ESTIMATE): November 8, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 6, 2015
• Last Update Submitted That Met QC Criteria: April 2, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: polymorphism; CYP3A5; maraviroc
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: NA_00078492