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

Healthy Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01980329
• Other study ID #: NA_00078492
• Status: Completed
• Phase: Phase 1
• First received: November 4, 2013
• Last updated: April 2, 2015
• Start date: January 2013
• Est. completion date: March 2014

Study information

• Verified date: April 2015
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cytochrome P450 CYP3A5 Enzyme Polymorphism
• Healthy Subjects
• Pharmacokinetics of Maraviroc

Intervention

Drug:
• Maraviroc

Locations

Country	Name	City	State
United States	The Johns Hopkins University School of Medicine Division of Clinical Pharmacology	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve		0-32 hour post dose administration	No
Secondary	Clearance		0-32 hr post dose administration	No
Secondary	Plasma peak concentration		0-32 hr post dose administration	No
Secondary	Plasma half-life		0-32 hr post dose administration	No
Secondary	Urinary metabolic ratio		0-32 hr post dose administration	No