Clincosm LogoSign in Get a demo

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

Sponsor
Johns Hopkins University (Other)
Overall Status
Completed
CT.gov ID
NCT01980329
Collaborator
(none)
24
Enrollment
1
Location
1
Arm
13.9
Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 1

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 CYP3A51 alleles), 8 heterozygous (1 CYP3A51 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Polymorphic Effects of Cytochrome P450 3A5 on Pharmacokinetics of Maraviroc and Its Metabolites
Study Start Date :
Jan 1, 2013
Actual Primary Completion Date :
Mar 1, 2014
Actual Study Completion Date :
Mar 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Maraviroc

single oral administration of 300 mg maraviroc

Drug: Maraviroc
Other Names:
  • Selzentry

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Area under the plasma concentration-time curve [0-32 hour post dose administration]

    Secondary Outcome Measures

    1. Clearance [0-32 hr post dose administration]

    2. Plasma peak concentration [0-32 hr post dose administration]

    3. Plasma half-life [0-32 hr post dose administration]

    4. Urinary metabolic ratio [0-32 hr post dose administration]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Johns Hopkins University School of Medicine Division of Clinical Pharmacology Baltimore Maryland United States 21210

    Sponsors and Collaborators

    • Johns Hopkins University

    Investigators

    • Principal Investigator: Namandje N Bumpus, Ph.D, Johns Hopkins University
    • Principal Investigator: Craig W Hendrix, MD, Johns Hopkins University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Namandjé N. Bumpus, PhD, Assistant Professor, Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT01980329
    Other Study ID Numbers:
    • NA_00078492
    First Posted:
    Nov 8, 2013
    Last Update Posted:
    Apr 6, 2015
    Last Verified:
    Apr 1, 2015
    Keywords provided by Namandjé N. Bumpus, PhD, Assistant Professor, Johns Hopkins University
    CYP3A5
    maraviroc
    polymorphism
    Additional relevant MeSH terms:
    Maraviroc

    Study Results

    No Results Posted as of Apr 6, 2015