Clinical trial NCT01980329: Polymorphic Effects of Cytochrome P450 3A5 on Pharmacokinetics of Maraviroc and Its Metabolites
Official title: Polymorphic Effects of Cytochrome P450 3A5 on Pharmacokinetics of Maraviroc and Its Metabolites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cytochrome P450 CYP3A5 Enzyme Polymorphism
Healthy Subjects
Pharmacokinetics of Maraviroc
Keywords: CYP3A5
maraviroc
polymorphism
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2013-11-08
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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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Eligibility criteria: 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

Primary outcomes:
measure: Area under the plasma concentration-time curve
timeFrame: 0-32 hour post dose administration
Secondary outcomes:
measure: Clearance
timeFrame: 0-32 hr post dose administration
measure: Plasma peak concentration
timeFrame: 0-32 hr post dose administration
measure: Plasma half-life
timeFrame: 0-32 hr post dose administration
measure: Urinary metabolic ratio
timeFrame: 0-32 hr post dose administration
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins University School of Medicine Division of Clinical Pharmacology
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Namandje N Bumpus, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Craig W Hendrix, MD
role: PRINCIPAL_INVESTIGATOR
References: