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

Phase 1

Completed

• Conditions: Pharmacokinetics of Maraviroc; Cytochrome P450 CYP3A5 Enzyme Polymorphism; Healthy Subjects
• Interventions: Drug: Maraviroc

• Registration Number: NCT01980329
• Lead Sponsor: Johns Hopkins University

Brief Summary

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

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 Timeline

• Study Start: 2013-01
• Study First Submitted: 2013-11-04
• Study First Submitted QC: 2013-11-04
• Study First Posted: 2013-11-08
• Primary Completion: 2014-03
• Study Completion: 2014-03
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-02
• Last Update Posted: 2015-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Maraviroc	Maraviroc	single oral administration of 300 mg maraviroc

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve	0-32 hour post dose administration

Secondary Outcome Measures

Name	Time	Method
Plasma peak concentration	0-32 hr post dose administration
Plasma half-life	0-32 hr post dose administration
Clearance	0-32 hr post dose administration
Urinary metabolic ratio	0-32 hr post dose administration

Trial Locations

Locations (1)

The Johns Hopkins University School of Medicine Division of Clinical Pharmacology; 🇺🇸 Baltimore, Maryland, United States