Phase 1
Completed N=47
THE EFFECT OF CYP3A5 GENOTYPE ON THE PHARMACOKINETICS OF MARAVIROC
Healthy Subjects
Source: ClinicalTrials.gov NCT02625207 ↗
Enrolled (actual)
47
Serious AEs
0.0%
Results posted
Apr 2017
Primary outcomePrimary: Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc — 3441; 2954; 2181; 2947 nanogram*hour per milliliter (ng*hr/mL) — p=0.1318
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc |
3441; 2954; 2181; 2947 | 0.1318 |
| PRIMARY Part 2: Area Under The Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) of Maraviroc |
4413; 3645 | 0.0531 |
| PRIMARY 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) |
0.02172; 0.03564; 0.04312; 0.01585; 0.02577; 0.02621 | 0.0106 sig |
| SECONDARY Part 1: Average Plasma Concentration (Cavg) of Maraviroc |
286.8; 246.2; 181.6; 245.8 | 0.1338 |
| SECONDARY Part 2: Average Plasma Concentration (Cavg) of Maraviroc |
184.1; 151.7 | 0.0507 |
| SECONDARY Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc |
863.9; 754.0; 529.0; 731.0 | 0.1997 |
| SECONDARY Part 2: Maximum Observed Plasma Concentration (Cmax) of Maraviroc |
633.6; 432.9 | 0.0505 |
| SECONDARY Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose |
59.84; 63.09; 45.32; 63.10 | 0.6761 |
| SECONDARY Part 2: Plasma Concentration of Maraviroc at 24 Hours Post-dose |
56.56; 56.34 | 0.9713 |
| SECONDARY Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc |
3.00; 2.00; 2.00; 2.01 | — |
| SECONDARY Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc |
3.00; 3.02 | — |
| SECONDARY Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc |
77.09; 108.7; 96.98; 48.24; 91.42; 79.92 | — |
| SECONDARY Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc |
6.420; 9.049; 8.074; 4.018; 7.615; 6.658 | — |
| SECONDARY Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc |
18.14; 24.18; 20.52; 11.22; 21.95; 18.96 | — |
| SECONDARY Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc |
3.00; 2.00; 2.00; 3.00; 3.00; 2.00 | — |
| SECONDARY Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose |
0.6249; 2.748; 2.226; 0.9213; 0.6290; 1.658 | — |
| SECONDARY Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
3; 0; 0; 3; 0; 0 | — |
| SECONDARY Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
2; 1; 0; 0 | — |
| SECONDARY Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities |
0; 0; 0; 0 | — |
| SECONDARY Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities |
0; 0 | — |
| SECONDARY Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities |
0; 0; 0; 0 | — |
| SECONDARY Part 2: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities |
0; 0 | — |
| SECONDARY Part 1: Number of Participants With Laboratory Abnormalities |
1; 5; 0; 2 | — |
| SECONDARY Part 2: Number of Participants With Laboratory Abnormalities |
1; 3 | — |
Eligibility Criteria
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 /=140 mm Hg (systolic) 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
Data sourced from ClinicalTrials.gov (NCT02625207). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.