Trial Outcomes & Findings for THE EFFECT OF CYP3A5 GENOTYPE ON THE PHARMACOKINETICS OF MARAVIROC (NCT NCT02625207)
NCT ID: NCT02625207
Last Updated: 2017-04-17
Results Overview
AUC (0-12) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
47 participants
Primary outcome timeframe
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Results posted on
2017-04-17
Participant Flow
The study was conducted in two parts (Part 1 and 2). Participants were assigned to treatment into 4 cohorts in Part 1 (Cohort 1, 2, 3, 4) and into 2 cohorts in part 2 (Cohort 1, 3).
Participant milestones
| Measure |
Part 1 and Part 2: Cohort 1 -No CYP3A5*1 Alleles
African-American participants with no CYP3A5\*1 alleles, received maraviroc 300 milligram (mg) tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1, followed by maraviroc 150 mg tablet once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2.
|
Part 1: Cohort 2 - One CYP3A5*1 Allele
African-American participants with one CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Part 1 and 2: Cohort 3 - Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1, followed by maraviroc 150 mg tablet once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2.
|
Part 1: Cohort 4 - No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
|---|---|---|---|---|
|
Part 1 (6 Days)
STARTED
|
11
|
12
|
12
|
12
|
|
Part 1 (6 Days)
COMPLETED
|
11
|
12
|
12
|
12
|
|
Part 1 (6 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Part 2 (11 Days)
STARTED
|
11
|
0
|
12
|
0
|
|
Part 2 (11 Days)
COMPLETED
|
11
|
0
|
12
|
0
|
|
Part 2 (11 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
THE EFFECT OF CYP3A5 GENOTYPE ON THE PHARMACOKINETICS OF MARAVIROC
Baseline characteristics by cohort
| Measure |
Part 1 and Part 2: Cohort 1 -No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1, followed by maraviroc 150 mg tablet once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2.
|
Part 1: Cohort 2 - One CYP3A5*1 Allele
n=12 Participants
African-American participants with one CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Part 1 and 2: Cohort 3 - Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1, followed by maraviroc 150 mg tablet once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2.
|
Part 1: Cohort 4 - No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
37.3 years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
38.3 years
STANDARD_DEVIATION 10.4 • n=7 Participants
|
34.6 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
48.2 years
STANDARD_DEVIATION 6 • n=4 Participants
|
39.6 years
STANDARD_DEVIATION 10.6 • n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
43 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: Pharmacokinetic (PK) parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
AUC (0-12) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc
|
2181 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 27
|
2947 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 23
|
3441 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 24
|
2954 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 23
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
AUC (0-24) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Area Under The Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) of Maraviroc
|
—
|
—
|
4413 ng*hr/mL
Geometric Coefficient of Variation 20
|
3645 ng*hr/mL
Geometric Coefficient of Variation 25
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
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.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
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)
PF-06927573
|
0.02040 ratio
Geometric Coefficient of Variation 27
|
0.02099 ratio
Geometric Coefficient of Variation 21
|
0.02048 ratio
Geometric Coefficient of Variation 14
|
0.02427 ratio
Geometric Coefficient of Variation 38
|
|
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)
PF-6857639
|
0.04312 ratio
Geometric Coefficient of Variation 32
|
0.01585 ratio
Geometric Coefficient of Variation 24
|
0.02172 ratio
Geometric Coefficient of Variation 31
|
0.03564 ratio
Geometric Coefficient of Variation 27
|
|
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)
PF-6857640
|
0.02797 ratio
Geometric Coefficient of Variation 32
|
0.02338 ratio
Geometric Coefficient of Variation 14
|
0.02577 ratio
Geometric Coefficient of Variation 11
|
0.02621 ratio
Geometric Coefficient of Variation 27
|
|
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)
PF-06927572
|
0.02795 ratio
Geometric Coefficient of Variation 37
|
0.02774 ratio
Geometric Coefficient of Variation 29
|
0.02766 ratio
Geometric Coefficient of Variation 19
|
0.02908 ratio
Geometric Coefficient of Variation 35
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
Cavg is the average plasma concentration of maraviroc during the 0 to 12 hour time period. It was calculated as area under the plasma concentration-time curve from 0 to 12 hours (AUC \[0-12\]) divided by 12.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Average Plasma Concentration (Cavg) of Maraviroc
|
181.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 27
|
245.8 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
286.8 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 24
|
246.2 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
Cavg is the average plasma concentration of maraviroc during the 0 to 24 hour time period. It was calculated as area under the plasma concentration-time curve from 0 to 24 hours (AUC \[0-24\]) divided by 24.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Average Plasma Concentration (Cavg) of Maraviroc
|
—
|
—
|
184.1 ng/mL
Geometric Coefficient of Variation 20
|
151.7 ng/mL
Geometric Coefficient of Variation 25
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc
|
529.0 ng/mL
Geometric Coefficient of Variation 34
|
731.0 ng/mL
Geometric Coefficient of Variation 33
|
863.9 ng/mL
Geometric Coefficient of Variation 29
|
754.0 ng/mL
Geometric Coefficient of Variation 29
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Maximum Observed Plasma Concentration (Cmax) of Maraviroc
|
—
|
—
|
633.6 ng/mL
Geometric Coefficient of Variation 37
|
432.9 ng/mL
Geometric Coefficient of Variation 53
|
SECONDARY outcome
Timeframe: 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose
|
45.32 ng/mL
Geometric Coefficient of Variation 35
|
63.10 ng/mL
Geometric Coefficient of Variation 24
|
59.84 ng/mL
Geometric Coefficient of Variation 36
|
63.09 ng/mL
Geometric Coefficient of Variation 27
|
SECONDARY outcome
Timeframe: 24 hours post-dose on Day 10Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Plasma Concentration of Maraviroc at 24 Hours Post-dose
|
—
|
—
|
56.56 ng/mL
Geometric Coefficient of Variation 20
|
56.34 ng/mL
Geometric Coefficient of Variation 30
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc
|
2.00 hour
Interval 0.517 to 4.0
|
2.01 hour
Interval 0.5 to 3.05
|
3.00 hour
Interval 2.0 to 4.0
|
2.00 hour
Interval 0.5 to 3.0
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc
|
—
|
—
|
3.00 hour
Interval 1.07 to 6.0
|
3.02 hour
Interval 1.0 to 6.02
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
AUC (0-12) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose. Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc
PF-6857639
|
96.98 ng*hr/mL
Geometric Coefficient of Variation 29
|
48.24 ng*hr/mL
Geometric Coefficient of Variation 32
|
77.09 ng*hr/mL
Geometric Coefficient of Variation 32
|
108.7 ng*hr/mL
Geometric Coefficient of Variation 44
|
|
Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc
PF-6857640
|
62.86 ng*hr/mL
Geometric Coefficient of Variation 26
|
71.15 ng*hr/mL
Geometric Coefficient of Variation 23
|
91.42 ng*hr/mL
Geometric Coefficient of Variation 22
|
79.92 ng*hr/mL
Geometric Coefficient of Variation 44
|
|
Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc
PF-06927572
|
62.80 ng*hr/mL
Geometric Coefficient of Variation 28
|
84.32 ng*hr/mL
Geometric Coefficient of Variation 33
|
98.14 ng*hr/mL
Geometric Coefficient of Variation 23
|
88.63 ng*hr/mL
Geometric Coefficient of Variation 49
|
|
Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc
PF-06927573
|
45.86 ng*hr/mL
Geometric Coefficient of Variation 27
|
63.88 ng*hr/mL
Geometric Coefficient of Variation 28
|
72.67 ng*hr/mL
Geometric Coefficient of Variation 28
|
73.92 ng*hr/mL
Geometric Coefficient of Variation 53
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
Cavg is the average plasma concentration of metabolites of maraviroc during the 0 to 12 hour time period. It was calculated as area under the plasma concentration-time curve from 0 to 12 hours (AUC \[0-12\]) divided by 12. Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc
PF-6857639
|
8.074 ng/mL
Geometric Coefficient of Variation 29
|
4.018 ng/mL
Geometric Coefficient of Variation 32
|
6.420 ng/mL
Geometric Coefficient of Variation 32
|
9.049 ng/mL
Geometric Coefficient of Variation 44
|
|
Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc
PF-6857640
|
5.239 ng/mL
Geometric Coefficient of Variation 26
|
5.930 ng/mL
Geometric Coefficient of Variation 23
|
7.615 ng/mL
Geometric Coefficient of Variation 22
|
6.658 ng/mL
Geometric Coefficient of Variation 44
|
|
Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc
PF-06927572
|
5.232 ng/mL
Geometric Coefficient of Variation 28
|
7.029 ng/mL
Geometric Coefficient of Variation 33
|
8.179 ng/mL
Geometric Coefficient of Variation 23
|
7.383 ng/mL
Geometric Coefficient of Variation 49
|
|
Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc
PF-06927573
|
3.821 ng/mL
Geometric Coefficient of Variation 27
|
5.323 ng/mL
Geometric Coefficient of Variation 28
|
6.056 ng/mL
Geometric Coefficient of Variation 28
|
6.165 ng/mL
Geometric Coefficient of Variation 53
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc
PF-6857639
|
20.52 ng/mL
Geometric Coefficient of Variation 34
|
11.22 ng/mL
Geometric Coefficient of Variation 37
|
18.14 ng/mL
Geometric Coefficient of Variation 23
|
24.18 ng/mL
Geometric Coefficient of Variation 55
|
|
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc
PF-6857640
|
15.00 ng/mL
Geometric Coefficient of Variation 30
|
16.48 ng/mL
Geometric Coefficient of Variation 28
|
21.95 ng/mL
Geometric Coefficient of Variation 28
|
18.96 ng/mL
Geometric Coefficient of Variation 56
|
|
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc
PF-06927572
|
15.31 ng/mL
Geometric Coefficient of Variation 32
|
19.91 ng/mL
Geometric Coefficient of Variation 35
|
22.88 ng/mL
Geometric Coefficient of Variation 18
|
20.67 ng/mL
Geometric Coefficient of Variation 58
|
|
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc
PF-06927573
|
10.86 ng/mL
Geometric Coefficient of Variation 34
|
15.27 ng/mL
Geometric Coefficient of Variation 35
|
17.39 ng/mL
Geometric Coefficient of Variation 32
|
17.64 ng/mL
Geometric Coefficient of Variation 66
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc
PF-6857639
|
2.00 hour
Interval 0.533 to 4.0
|
3.00 hour
Interval 0.5 to 4.0
|
3.00 hour
Interval 1.0 to 4.0
|
2.00 hour
Interval 0.5 to 3.0
|
|
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc
PF-6857640
|
2.00 hour
Interval 0.533 to 4.0
|
3.00 hour
Interval 1.0 to 4.0
|
3.00 hour
Interval 1.0 to 4.0
|
2.00 hour
Interval 0.5 to 3.02
|
|
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc
PF-06927572
|
1.52 hour
Interval 0.5 to 4.0
|
3.00 hour
Interval 1.0 to 4.0
|
3.00 hour
Interval 1.0 to 4.0
|
2.00 hour
Interval 0.5 to 3.0
|
|
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc
PF-06927573
|
2.00 hour
Interval 0.567 to 4.0
|
3.00 hour
Interval 1.0 to 4.0
|
3.00 hour
Interval 1.0 to 4.0
|
2.00 hour
Interval 0.5 to 3.0
|
SECONDARY outcome
Timeframe: 12 hour post-dose on Day 5Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose
PF-6857639
|
2.226 ng/mL
Geometric Coefficient of Variation 32
|
0.9213 ng/mL
Geometric Coefficient of Variation 38
|
0.6249 ng/mL
Geometric Coefficient of Variation 7399
|
2.748 ng/mL
Geometric Coefficient of Variation 43
|
|
Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose
PF-6857640
|
1.134 ng/mL
Geometric Coefficient of Variation 29
|
1.300 ng/mL
Geometric Coefficient of Variation 33
|
0.6290 ng/mL
Geometric Coefficient of Variation 7164
|
1.658 ng/mL
Geometric Coefficient of Variation 40
|
|
Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose
PF-06927572
|
1.071 ng/mL
Geometric Coefficient of Variation 29
|
1.385 ng/mL
Geometric Coefficient of Variation 40
|
0.6242 ng/mL
Geometric Coefficient of Variation 7051
|
1.752 ng/mL
Geometric Coefficient of Variation 45
|
|
Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose
PF-06927573
|
0.8550 ng/mL
Geometric Coefficient of Variation 26
|
1.175 ng/mL
Geometric Coefficient of Variation 32
|
0.5396 ng/mL
Geometric Coefficient of Variation 6283
|
1.629 ng/mL
Geometric Coefficient of Variation 55
|
SECONDARY outcome
Timeframe: Baseline up to end of study (up to 6 days)Population: Safety analysis set included all participants who received at least 1 dose of study drug.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 6 days that were absent before treatment or that worsened relative to pre-treatment state.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
0 participants
|
3 participants
|
3 participants
|
0 participants
|
|
Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline up to end of study (up to 11 days)Population: Safety analysis set included all participants who received at least 1 dose of study drug. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 11 days that were absent before treatment or that worsened relative to pretreatment state.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
—
|
—
|
2 participants
|
1 participants
|
|
Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
—
|
—
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 6Population: Safety analysis set included all participants who received at least 1 dose of study drug.
Criteria for clinically significant vital sign abnormalities included supine/sitting pulse rate of less than (\<) 40 beats per minute (bpm) or greater than (\>)120 bpm, standing pulse rate of \<40 bpm or \>140 bpm, supine systolic blood pressure (SBP) and standing SBP of \<90 millimeter of mercury (mm Hg), greater than or equal to (\>=) 30 mm Hg, supine diastolic blood pressure (DBP) and standing DBP of \<50 mm Hg, \>=20 mm Hg.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 11Population: Safety analysis set included all participants who received at least 1 dose of study drug. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
Criteria for clinically significant vital sign abnormalities included supine/sitting pulse rate of \<40 bpm or \>120 bpm, standing pulse rate of \<40 bpm or \>140 bpm, supine SBP and standing SBP of \<90 mm Hg, \>=30 mm Hg, supine DBP and standing DBP of \<50 mm Hg, \>=20 mm Hg.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities
|
—
|
—
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 6Population: Safety analysis set included all participants who received at least 1 dose of study drug.
Criteria for ECG abnormalities: Maximum PR interval of \>=300 milliseconds (msec), maximum QRS interval \>=140 msec, maximum QTCF interval (Fridericia's correction) of 450 to \<480 msec, 480 to \<500 msec and \>=500 msec, maximum increase of \>=25 percent for baseline values of \>200 msec and \>=50 percent for baseline values of less than or equal to (\<=) 200 msec for PR interval, maximum increase from baseline of \>=50 percent for QRS interval, maximum increase from baseline of \>=30 msec to \<60 msec and maximum increase from baseline of \>60 msec in QTCF interval (Fridericia's Correction).
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 11Population: Safety analysis set included all participants who received at least 1 dose of study drug. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
Criteria for ECG abnormalities: Maximum PR interval of \>=300 msec, maximum QRS interval \>=140 msec, maximum QTCF interval (Fridericia's correction) of 450 to \<480 msec, 480 to \<500 msec and \>=500 msec, maximum increase of \>=25 percent for baseline values of \>200 msec and \>=50 percent for baseline values of \<=200 msec for PR interval, maximum increase from baseline of \>=50 percent for QRS interval, maximum increase from baseline of \>=30 msec to \<60 msec and maximum increase from baseline of \>60 msec in QTCF interval (Fridericia's Correction).
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
|
—
|
—
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 6Population: Safety analysis set included all participants who received at least 1 dose of study drug.
Criteria: Hemoglobin; hematocrit; red blood cell count: \<0.8\*lower limit of normal, (LLN), mean corpuscular volume; mean corpuscular hemoglobin concentration; mean platelet volume:\<0.9\*LLN or \>1.1\* upper limit of normal (ULN), platelet: \<0.5\*LLN or \>1.75\*ULN, white blood cells \<0.6\*LLN or \>1.5\*ULN, lymphocyte; neutrophil: \<0.8\*LLN or \>1.2\*ULN, basophil; eosinophil; monocyte:\>1.2\*ULN, bilirubin (total, direct, indirect) \>1.5\*ULN, aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase:\>3.0\*ULN, total protein; albumin:\<0.8\*LLN or \>1.2\*ULN; creatinine: \>1.3\*ULN, uric acid\>1.2\*ULN, sodium\<0.95\*LLN or \>1.05\*ULN, potassium; chloride; calcium; bicarbonate:\<0.9\*LLN or \>1.1\*ULN, glucose \<0.6\*LLN or \>1.5\*ULN, urine specific gravity \<1.003, urine pH \<4.5 or \>8, urine glucose or ketones (qualitative) \>=1, urine protein; urine blood/hemoglobin \>=1, urobilinogen; bilirubin; nitrite; leukocyte esterase \>=1.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
n=12 Participants
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 1: Number of Participants With Laboratory Abnormalities
|
0 participants
|
2 participants
|
1 participants
|
5 participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 11Population: Safety analysis set included all participants who received at least 1 dose of study drug. Data for Part 2 was planned to be analyzed only in Cohorts 1 and 3, as pre specified in protocol.
Criteria: Hemoglobin; hematocrit; red blood cell count: \<0.8\*LLN, mean corpuscular volume; mean corpuscular hemoglobin concentration; mean platelet volume: \<0.9\*LLN or \>1.1\*ULN, platelet: \<0.5\*LLN or \>1.75\*ULN, white blood cells \<0.6\*LLN or \>1.5\*ULN, lymphocyte; neutrophil: \<0.8\*LLN or \>1.2\*ULN, basophil; eosinophil; monocyte: \>1.2\*ULN, bilirubin (total, direct, indirect) \>1.5\*ULN, aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase: \>3.0\*ULN, total protein; albumin: \<0.8\*LLN or \>1.2\*ULN; creatinine: \>1.3\*ULN, uric acid \>1.2\*ULN, sodium\<0.95\*LLN or \>1.05\*ULN, potassium; chloride; calcium; bicarbonate:\<0.9\*LLN or \>1.1\*ULN, glucose \<0.6\*LLN or \>1.5\*ULN, urine specific gravity \<1.003, urine pH \<4.5 or \>8, urine glucose or ketones (qualitative) \>=1, urine protein; urine blood/hemoglobin \>=1, urobilinogen; bilirubin; nitrite; leukocyte esterase \>=1.
Outcome measures
| Measure |
Cohort 3- Two CYP3A5*1 Alleles
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 4- No CYP3A5*1 Alleles
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Cohort 1- No CYP3A5*1 Alleles
n=11 Participants
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Cohort 3- Two CYP3A5*1 Alleles
n=12 Participants
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|
|
Part 2: Number of Participants With Laboratory Abnormalities
|
—
|
—
|
1 participants
|
3 participants
|
Adverse Events
Part 1: Cohort 1- No CYP3A5*1 Alleles
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part 1: Cohort 2- One CYP3A5*1 Allele
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Part 1: Cohort 3- Two CYP3A5*1 Alleles
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Part 1: Cohort 4 - No CYP3A5*1 Alleles
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part 2: Cohort 1- No CYP3A5*1 Alleles
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 2: Cohort 3- Two CYP3A5*1 Alleles
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part 1: Cohort 1- No CYP3A5*1 Alleles
n=11 participants at risk
African-American participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Part 1: Cohort 2- One CYP3A5*1 Allele
n=12 participants at risk
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Part 1: Cohort 3- Two CYP3A5*1 Alleles
n=12 participants at risk
African-American participants with two CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Part 1: Cohort 4 - No CYP3A5*1 Alleles
n=12 participants at risk
Caucasian participants with no CYP3A5\*1 alleles, received maraviroc 300 mg tablet orally twice daily from Day 1 to Day 4 and once only in the morning of Day 5 in Part 1.
|
Part 2: Cohort 1- No CYP3A5*1 Alleles
n=11 participants at risk
African-American participants with no CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
Part 2: Cohort 3- Two CYP3A5*1 Alleles
n=12 participants at risk
African-American participants with two CYP3A5\*1 alleles, received maraviroc 150 mg tablet orally once daily along with darunavir/cobicistat 800/150 mg tablet once daily from Day 1 to Day 10 in Part 2 .
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Dry mouth
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Ear and labyrinth disorders
Ear discomfort
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
8.3%
1/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Gastrointestinal disorders
Flatulence
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
8.3%
1/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
General disorders
Pain
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
General disorders
Thirst
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
8.3%
1/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
16.7%
2/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Renal and urinary disorders
Polyuria
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Vascular disorders
Hot flush
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
9.1%
1/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
0.00%
0/11
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
8.3%
1/12
Adverse events were collected and reported for Part 1 and Part 2 separately.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER