THE EFFECT OF CYP3A5 GENOTYPE ON THE PHARMACOKINETICS OF MARAVIROC

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-06

Study Completion Date

2016-03-26

Brief Summary

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This will be an open-label, parallel group, multiple dose study in approximately 48 healthy male or female subjects of African American and Caucasian self-reported race, to assess the effect of CYP3A5 genotype on the PK of MVC and CYP3A5-derived metabolites. Maraviroc and CYP3A5-derived metabolite PK will also be compared between African-Americans and Caucasians in subjects carrying two copies of the dysfunctional CYP3A5 alleles (\*3, \*6, and/or \*7).

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Detailed Description

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This will be an open-label, parallel group, multiple dose study in approximately 48 healthy male or female subjects of African American and Caucasian self-reported race, to assess the effect of CYP3A5 genotype on the PK of MVC and CYP3A5-derived metabolites. Maraviroc and CYP3A5-derived metabolite PK will also be compared between African-Americans and Caucasians in subjects carrying two copies of the dysfunctional CYP3A5 alleles (\*3, \*6, and/or \*7).

Dysfunctional genetic variants for CYP3A5, CYP3A4 and SLCO1B1 will be genotyped for subjects who participate in the pre-screening. Subjects who meet the inclusion/exclusion criteria for study participation will be placed into the study cohorts based on race and the number of functional (\*1) and dysfunctional CYP3A5 alleles (\*3, \*6, and \*7) CYP3A5 alleles.

Cohort 1 (n=12; African-American): No CYP3A5\*1 alleles (poor metabolizer). Cohort 2 (n=12; African-American): One CYP3A5\*1 allele (intermediate metabolizer).

Cohort 3 (n=12; African-American): Two CYP3A5\*1 alleles (extensive metabolizer).

Cohort 4 (n=12; Caucasian): No CYP3A5\*1 alleles (poor metabolizer).

Study Treatments:

Part 1 Days 1-5: Maraviroc 300 mg BID in fasted state (AM dose only on Day 5). Part 2 (Cohorts 1 and 3 only) Days 1-10: Maraviroc 150 mg QD plus darunavir/cobicistat 800/150 mg QD with food.

Pharmacokinetics of MVC, PF-6857639, PF-6857640 and other hydroxylated metabolites with formation mediated by CYP3A5 (if present) will be assessed on Part 1, Day 5 and Part 2, Days 10-11. Blood samples will be collected for a full PK profile.

Subjects will be confined to the Clinical Research Unit (CRU) the day prior to dosing on Day 1 (Day 0) and discharged on Part 1, Day 6 and on Part 2, Day 11 (Cohorts 1 and 3 only). Subjects enrolled into Cohorts 1 and 3 may be confined to the CRU without the need to be discharged between Part 1 and Part 2.

Conditions

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Healthy Subjects

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1

African-Americans with No CYP3A5\*1 alleles (poor metabolizer)

Group Type EXPERIMENTAL

Maraviroc (Part 1)

Intervention Type DRUG

300 mg twice daily x 5 days

Maraviroc (Part 2)

Intervention Type DRUG

150 mg once daily x 10 days

Darunavir/cobicistat (Part 2)

Intervention Type DRUG

800/150 mg once daily x 10 days

Cohort 2

African-Americans with One CYP3A5\*1 allele (intermediate metabolizer)

Group Type EXPERIMENTAL

Maraviroc (Part 1)

Intervention Type DRUG

300 mg twice daily x 5 days

Cohort 3

African-Americans with Two CYP3A5\*1 alleles (extensive metabolizer)

Group Type EXPERIMENTAL

Maraviroc (Part 1)

Intervention Type DRUG

300 mg twice daily x 5 days

Maraviroc (Part 2)

Intervention Type DRUG

150 mg once daily x 10 days

Darunavir/cobicistat (Part 2)

Intervention Type DRUG

800/150 mg once daily x 10 days

Cohort 4

Caucasians with No CYP3A5\*1 alleles (poor metabolizer)

Group Type EXPERIMENTAL

Maraviroc (Part 1)

Intervention Type DRUG

300 mg twice daily x 5 days

Interventions

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Maraviroc (Part 1)

300 mg twice daily x 5 days

Intervention Type DRUG

Maraviroc (Part 2)

150 mg once daily x 10 days

Intervention Type DRUG

Darunavir/cobicistat (Part 2)

800/150 mg once daily x 10 days

Intervention Type DRUG

Other Intervention Names

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Selzentry Selzentry Prezcobix

Eligibility Criteria

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Inclusion Criteria

* Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs)
* Healthy female subjects and/or male subjects of African-American/Black or Caucasian race

Exclusion Criteria

* History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males
* Treatment with an investigational drug within 30 days
* Screening supine blood pressure \<90 or \>/=140 mm Hg (systolic) or \<60 or \>/= 90 mm Hg (diastolic), following at least 5 minutes of supine rest
* Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.
* Use of tobacco- or nicotine-containing products in excess of the equivalent of 5 cigarettes per day
* Subjects who have a CYP3A4\*22 allele and/or have a SLCO1B1 \*5 or \*15 allele

Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes