NCT02625207

Brief Summary

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Nov 2015

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 20, 2015

Completed
17 days until next milestone

Study Start

First participant enrolled

November 6, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 9, 2015

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 26, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 26, 2016

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

April 17, 2017

Completed
Last Updated

April 17, 2017

Status Verified

March 1, 2017

Enrollment Period

5 months

First QC Date

October 20, 2015

Results QC Date

March 1, 2017

Last Update Submit

March 1, 2017

Conditions

Healthy Subjects

Keywords

Maraviroc, CYP3A5, pharmacokinetics, pharmacogenomics

Outcome Measures

Primary Outcomes (3)

  • Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc

    AUC (0-12) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose.

    Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5

  • Part 2: Area Under The Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) of Maraviroc

    AUC (0-24) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose.

    Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10

  • Part 1: Metabolite to Parent Ratio for Area Under the Concentration-Time Curve From Time 0 to 12 Hours for Maraviroc and Its Metabolites (MRAUC12)

    MRAUC12 is the ratio of AUC12 of maraviroc to AUC12 of maraviroc's metabolites. Metabolites of Maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573. AUC12 is the area under the plasma concentration-time profile from time 0 to 12 hours post-dose.

    Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5

Secondary Outcomes (21)

  • Part 1: Average Plasma Concentration (Cavg) of Maraviroc

    Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5

  • Part 2: Average Plasma Concentration (Cavg) of Maraviroc

    Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10

  • Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc

    Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5

  • Part 2: Maximum Observed Plasma Concentration (Cmax) of Maraviroc

    Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10

  • Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose

    12 hours post-dose on Day 5

  • +16 more secondary outcomes

Study Arms (4)

Cohort 1

EXPERIMENTAL

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

Drug: Maraviroc (Part 1)Drug: Maraviroc (Part 2)Drug: Darunavir/cobicistat (Part 2)

Cohort 2

EXPERIMENTAL

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

Drug: Maraviroc (Part 1)

Cohort 3

EXPERIMENTAL

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

Drug: Maraviroc (Part 1)Drug: Maraviroc (Part 2)Drug: Darunavir/cobicistat (Part 2)

Cohort 4

EXPERIMENTAL

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

Drug: Maraviroc (Part 1)

Interventions

Maraviroc (Part 1)DRUG

300 mg twice daily x 5 days

Also known as: Selzentry
Cohort 1Cohort 2Cohort 3Cohort 4
Maraviroc (Part 2)DRUG

150 mg once daily x 10 days

Also known as: Selzentry
Cohort 1Cohort 3
Darunavir/cobicistat (Part 2)DRUG

800/150 mg once daily x 10 days

Also known as: Prezcobix
Cohort 1Cohort 3

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

  • Vourvahis M, McFadyen L, Nepal S, Valluri SR, Fang A, Fate GD, Wood LS, Marshall JC, Chan PLS, Nedderman A, Haynes J, Savage ME, Clark A, Smith KY, Heera J. No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV-1-Infected Subjects. J Clin Pharmacol. 2019 Jan;59(1):139-152. doi: 10.1002/jcph.1306. Epub 2018 Sep 7.

    PMID: 30192390DERIVED

Related Links

MeSH Terms

Interventions

MaravirocDarunavirCobicistatcobicistat mixture with darunavir

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsSulfonamidesAmidesCarbamatesAcids, AcyclicCarboxylic AcidsSulfonesSulfur CompoundsFuransThiazoles

Limitations and Caveats

As per change in planned analysis, calculation of metabolite PK parameters and statistical analyses were not conducted in Part 2, since substantial number of PK samples were below limit of quantitation, considered as non-reliable by investigator.

Results Point of Contact

Title
Pfizer ClinicalTrials.gov Call Center
Organization
Pfizer, Inc.
ClinicalTrials.gov_Inquiries@pfizer.com
1-800-718-1021

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 20, 2015

First Posted

December 9, 2015

Study Start

November 6, 2015

Primary Completion

March 26, 2016

Study Completion

March 26, 2016

Last Updated

April 17, 2017

Results First Posted

April 17, 2017

Record last verified: 2017-03

Locations

US(1)