Healthy Subjects
Conditions
Keywords
Maraviroc, CYP3A5, pharmacokinetics, pharmacogenomics
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).
Detailed description
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.
Interventions
DRUGMaraviroc (Part 1)
300 mg twice daily x 5 days
DRUGMaraviroc (Part 2)
150 mg once daily x 10 days
DRUGDarunavir/cobicistat (Part 2)
800/150 mg once daily x 10 days
Sponsors
Pfizer
ViiV Healthcare
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5 | AUC (0-12) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose. |
| Part 2: Area Under The Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) of Maraviroc | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10 | AUC (0-24) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose. |
| 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) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Part 2: Plasma Concentration of Maraviroc at 24 Hours Post-dose | 24 hours post-dose on Day 10 | — |
| Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5 | — |
| Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10 | — |
| Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5 | 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. |
| Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5 | 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. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5 | Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573. |
| Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5 | Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573. |
| 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 | 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. |
| Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to end of study (up to 6 days) | 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. |
| Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to end of study (up to 11 days) | 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. |
| Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities | Baseline up to Day 6 | 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. |
| Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities | Baseline up to Day 11 | 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. |
| Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | Baseline up to Day 6 | 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). |
| Part 2: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | Baseline up to Day 11 | 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). |
| Part 1: Number of Participants With Laboratory Abnormalities | Baseline up to Day 6 | 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. |
| Part 2: Number of Participants With Laboratory Abnormalities | Baseline up to Day 11 | 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. |
| Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | 12 hour post-dose on Day 5 | Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573. |
| 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 | 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. |
| 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 | — |
Countries
United States
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Part 1 and Part 2: Cohort 1 -No CYP3A5*1 Alleles 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. | 11 |
| 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. | 12 |
| 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. | 12 |
| 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. | 12 |
| Total | 47 |
Baseline characteristics
| Characteristic | Part 1 and Part 2: Cohort 1 -No CYP3A5*1 Alleles | Part 1: Cohort 2 - One CYP3A5*1 Allele | Part 1 and 2: Cohort 3 - Two CYP3A5*1 Alleles | Part 1: Cohort 4 - No CYP3A5*1 Alleles | Total |
|---|---|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 9.7 | 38.3 years STANDARD_DEVIATION 10.4 | 34.6 years STANDARD_DEVIATION 11.4 | 48.2 years STANDARD_DEVIATION 6 | 39.6 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 9 Participants | 12 Participants | 11 Participants | 11 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 11 | 0 / 12 | 0 / 12 | 3 / 12 | 2 / 11 | 1 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: Pharmacokinetic (PK) parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc | 3441 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc | 2954 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc | 2947 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
p-value: 0.131890% CI: [98.55, 138.26]Mixed Models Analysis
p-value: 0.136990% CI: [72.48, 101.68]Mixed Models Analysis
p-value: <0.000190% CI: [53.51, 75.07]Mixed Models Analysis
p-value: 0.003690% CI: [62.57, 87.13]Mixed Models Analysis
p-value: 0.003890% CI: [62.7, 87.31]Mixed Models Analysis
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)
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | 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 | 0.02172 ratio | Geometric Coefficient of Variation 31 |
| Cohort 1- No CYP3A5*1 Alleles | 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 | 0.02577 ratio | Geometric Coefficient of Variation 11 |
| Cohort 1- No CYP3A5*1 Alleles | 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 | 0.02766 ratio | Geometric Coefficient of Variation 19 |
| Cohort 1- No CYP3A5*1 Alleles | 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 | 0.02048 ratio | Geometric Coefficient of Variation 14 |
| Cohort 2- One CYP3A5*1 Allele | 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 | 0.02427 ratio | Geometric Coefficient of Variation 38 |
| Cohort 2- One CYP3A5*1 Allele | 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 | 0.02908 ratio | Geometric Coefficient of Variation 35 |
| Cohort 2- One CYP3A5*1 Allele | 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 | 0.02621 ratio | Geometric Coefficient of Variation 27 |
| Cohort 2- One CYP3A5*1 Allele | 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 | 0.03564 ratio | Geometric Coefficient of Variation 27 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 4- No CYP3A5*1 Alleles | 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 | 0.02099 ratio | Geometric Coefficient of Variation 21 |
| Cohort 4- No CYP3A5*1 Alleles | 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 | 0.01585 ratio | Geometric Coefficient of Variation 24 |
| Cohort 4- No CYP3A5*1 Alleles | 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 | 0.02338 ratio | Geometric Coefficient of Variation 14 |
| Cohort 4- No CYP3A5*1 Alleles | 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 | 0.02774 ratio | Geometric Coefficient of Variation 29 |
Comparison: Statistical analysis of PF -6857639 was estimated and reported.p-value: 0.010690% CI: [112.4, 167.15]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857639 was estimated and reported.p-value: 0.000190% CI: [134.54, 200.06]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857639 was estimated and reported.p-value: <0.000190% CI: [162.77, 242.05]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857639 was estimated and reported.p-value: 0.106190% CI: [99.65, 146.9]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857639 was estimated and reported.p-value: <0.000190% CI: [224.08, 330.33]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857640 was estimated and reported.p-value: 0.308190% CI: [94.05, 129.18]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857640 was estimated and reported.p-value: 0.858390% CI: [86.79, 119.2]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857640 was estimated and reported.p-value: 0.391390% CI: [92.6, 127.17]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857640 was estimated and reported.p-value: 0.486690% CI: [91.36, 124.6]Mixed Models Analysis
Comparison: Statistical analysis of PF -6857640 was estimated and reported.p-value: 0.05990% CI: [102.42, 139.69]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927572 was estimated and reported.p-value: 0.981690% CI: [80.47, 123.53]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927572 was estimated and reported.p-value: 0.697490% CI: [84.84, 130.24]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927572 was estimated and reported.p-value: 0.936390% CI: [81.54, 125.18]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927572 was estimated and reported.p-value: 0.75290% CI: [77.94, 118.52]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927572 was estimated and reported.p-value: 0.953690% CI: [81.69, 124.22]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927573 was estimated and reported.p-value: 0.824190% CI: [81.28, 117.18]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927573 was estimated and reported.p-value: 0.126190% CI: [98.69, 142.28]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927573 was estimated and reported.p-value: 0.970890% CI: [82.95, 119.59]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927573 was estimated and reported.p-value: 0.109990% CI: [70.29, 100.52]Mixed Models Analysis
Comparison: Statistical analysis of PF -06927573 was estimated and reported.p-value: 0.791390% CI: [81.29, 116.25]Mixed Models Analysis
Primary
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | 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 |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Area Under The Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) of Maraviroc | 3645 ng*hr/mL | Geometric Coefficient of Variation 25 |
p-value: 0.053190% CI: [70.33, 96.98]Mixed Models Analysis
Secondary
Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites 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. Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-06927572 | 98.14 ng*hr/mL | Geometric Coefficient of Variation 23 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-6857640 | 91.42 ng*hr/mL | Geometric Coefficient of Variation 22 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-6857639 | 77.09 ng*hr/mL | Geometric Coefficient of Variation 32 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-06927573 | 72.67 ng*hr/mL | Geometric Coefficient of Variation 28 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-06927573 | 73.92 ng*hr/mL | Geometric Coefficient of Variation 53 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-6857639 | 108.7 ng*hr/mL | Geometric Coefficient of Variation 44 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-6857640 | 79.92 ng*hr/mL | Geometric Coefficient of Variation 44 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-06927572 | 88.63 ng*hr/mL | Geometric Coefficient of Variation 49 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 3- Two CYP3A5*1 Alleles | 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 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-6857639 | 48.24 ng*hr/mL | Geometric Coefficient of Variation 32 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-6857640 | 71.15 ng*hr/mL | Geometric Coefficient of Variation 23 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-06927573 | 63.88 ng*hr/mL | Geometric Coefficient of Variation 28 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc | PF-06927572 | 84.32 ng*hr/mL | Geometric Coefficient of Variation 33 |
Secondary
Part 1: Average Plasma Concentration (Cavg) of Maraviroc
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cavg) of Maraviroc | 286.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Average Plasma Concentration (Cavg) of Maraviroc | 246.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cavg) of Maraviroc | 181.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cavg) of Maraviroc | 245.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
p-value: 0.133890% CI: [98.47, 138.18]Mixed Models Analysis
p-value: 0.13790% CI: [72.46, 101.68]Mixed Models Analysis
p-value: <0.000190% CI: [53.47, 75.04]Mixed Models Analysis
p-value: 0.003690% CI: [62.53, 87.09]Mixed Models Analysis
p-value: 0.003790% CI: [62.61, 87.2]Mixed Models Analysis
Secondary
Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-06927573 | 6.056 ng/mL | Geometric Coefficient of Variation 28 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-6857640 | 7.615 ng/mL | Geometric Coefficient of Variation 22 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-06927572 | 8.179 ng/mL | Geometric Coefficient of Variation 23 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-6857639 | 6.420 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-06927572 | 7.383 ng/mL | Geometric Coefficient of Variation 49 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-6857639 | 9.049 ng/mL | Geometric Coefficient of Variation 44 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-6857640 | 6.658 ng/mL | Geometric Coefficient of Variation 44 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-06927573 | 6.165 ng/mL | Geometric Coefficient of Variation 53 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-6857639 | 8.074 ng/mL | Geometric Coefficient of Variation 29 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-6857640 | 5.239 ng/mL | Geometric Coefficient of Variation 26 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-06927572 | 5.232 ng/mL | Geometric Coefficient of Variation 28 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-06927573 | 3.821 ng/mL | Geometric Coefficient of Variation 27 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-6857639 | 4.018 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-06927573 | 5.323 ng/mL | Geometric Coefficient of Variation 28 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-6857640 | 5.930 ng/mL | Geometric Coefficient of Variation 23 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc | PF-06927572 | 7.029 ng/mL | Geometric Coefficient of Variation 33 |
Secondary
Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc | 863.9 ng/mL | Geometric Coefficient of Variation 29 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc | 754.0 ng/mL | Geometric Coefficient of Variation 29 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc | 529.0 ng/mL | Geometric Coefficient of Variation 34 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc | 731.0 ng/mL | Geometric Coefficient of Variation 33 |
p-value: 0.199790% CI: [95.26, 146.63]Mixed Models Analysis
p-value: 0.294790% CI: [70.34, 108.28]Mixed Models Analysis
p-value: 0.000490% CI: [49.35, 75.97]Mixed Models Analysis
p-value: 0.007190% CI: [56.81, 86.63]Mixed Models Analysis
p-value: 0.013590% CI: [58.6, 89.36]Mixed Models Analysis
Secondary
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc
Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-6857639 | 18.14 ng/mL | Geometric Coefficient of Variation 23 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-6857640 | 21.95 ng/mL | Geometric Coefficient of Variation 28 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-06927572 | 22.88 ng/mL | Geometric Coefficient of Variation 18 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-06927573 | 17.39 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-6857640 | 18.96 ng/mL | Geometric Coefficient of Variation 56 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-06927572 | 20.67 ng/mL | Geometric Coefficient of Variation 58 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-06927573 | 17.64 ng/mL | Geometric Coefficient of Variation 66 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-6857639 | 24.18 ng/mL | Geometric Coefficient of Variation 55 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-06927572 | 15.31 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-6857640 | 15.00 ng/mL | Geometric Coefficient of Variation 30 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-06927573 | 10.86 ng/mL | Geometric Coefficient of Variation 34 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-6857639 | 20.52 ng/mL | Geometric Coefficient of Variation 34 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-06927573 | 15.27 ng/mL | Geometric Coefficient of Variation 35 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-6857640 | 16.48 ng/mL | Geometric Coefficient of Variation 28 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-6857639 | 11.22 ng/mL | Geometric Coefficient of Variation 37 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc | PF-06927572 | 19.91 ng/mL | Geometric Coefficient of Variation 35 |
Secondary
Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
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).
Time frame: Baseline up to Day 6
Population: Safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | 0 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | 0 participants |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | 0 participants |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | 0 participants |
Secondary
Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities
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.
Time frame: Baseline up to Day 6
Population: Safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 participants |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 participants |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 participants |
Secondary
Part 1: Number of Participants With Laboratory Abnormalities
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.
Time frame: Baseline up to Day 6
Population: Safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Number of Participants With Laboratory Abnormalities | 1 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Number of Participants With Laboratory Abnormalities | 5 participants |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Number of Participants With Laboratory Abnormalities | 0 participants |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Number of Participants With Laboratory Abnormalities | 2 participants |
Secondary
Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 participants |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 0 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 0 participants |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 participants |
Secondary
Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose
Time frame: 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose | 59.84 ng/mL | Geometric Coefficient of Variation 36 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose | 63.09 ng/mL | Geometric Coefficient of Variation 27 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose | 45.32 ng/mL | Geometric Coefficient of Variation 35 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose | 63.10 ng/mL | Geometric Coefficient of Variation 24 |
p-value: 0.676190% CI: [76.7, 117.24]Mixed Models Analysis
p-value: 0.677190% CI: [85.28, 130.35]Mixed Models Analysis
p-value: 0.033190% CI: [61.26, 93.64]Mixed Models Analysis
p-value: 0.010490% CI: [58.38, 88.4]Mixed Models Analysis
p-value: 0.010490% CI: [58.37, 88.39]Mixed Models Analysis
Secondary
Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose
Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Time frame: 12 hour post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-06927572 | 0.6242 ng/mL | Geometric Coefficient of Variation 7051 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-6857639 | 0.6249 ng/mL | Geometric Coefficient of Variation 7399 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-06927573 | 0.5396 ng/mL | Geometric Coefficient of Variation 6283 |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-6857640 | 0.6290 ng/mL | Geometric Coefficient of Variation 7164 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-6857639 | 2.748 ng/mL | Geometric Coefficient of Variation 43 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-06927573 | 1.629 ng/mL | Geometric Coefficient of Variation 55 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-06927572 | 1.752 ng/mL | Geometric Coefficient of Variation 45 |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-6857640 | 1.658 ng/mL | Geometric Coefficient of Variation 40 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-06927572 | 1.071 ng/mL | Geometric Coefficient of Variation 29 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-6857640 | 1.134 ng/mL | Geometric Coefficient of Variation 29 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-06927573 | 0.8550 ng/mL | Geometric Coefficient of Variation 26 |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-6857639 | 2.226 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-06927573 | 1.175 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-06927572 | 1.385 ng/mL | Geometric Coefficient of Variation 40 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-6857639 | 0.9213 ng/mL | Geometric Coefficient of Variation 38 |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose | PF-6857640 | 1.300 ng/mL | Geometric Coefficient of Variation 33 |
Secondary
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc | 3.00 hour |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc | 2.00 hour |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc | 2.00 hour |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc | 2.01 hour |
Secondary
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc
Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
Population: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-6857639 | 3.00 hour |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-06927572 | 3.00 hour |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-6857640 | 3.00 hour |
| Cohort 1- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-06927573 | 3.00 hour |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-06927572 | 2.00 hour |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-6857640 | 2.00 hour |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-06927573 | 2.00 hour |
| Cohort 2- One CYP3A5*1 Allele | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-6857639 | 2.00 hour |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-6857639 | 2.00 hour |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-06927572 | 1.52 hour |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-06927573 | 2.00 hour |
| Cohort 3- Two CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-6857640 | 2.00 hour |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-06927573 | 3.00 hour |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-6857640 | 3.00 hour |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-6857639 | 3.00 hour |
| Cohort 4- No CYP3A5*1 Alleles | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc | PF-06927572 | 3.00 hour |
Secondary
Part 2: Average Plasma Concentration (Cavg) of Maraviroc
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Average Plasma Concentration (Cavg) of Maraviroc | 184.1 ng/mL | Geometric Coefficient of Variation 20 |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Average Plasma Concentration (Cavg) of Maraviroc | 151.7 ng/mL | Geometric Coefficient of Variation 25 |
p-value: 0.050790% CI: [70.2, 96.77]Mixed Models Analysis
Secondary
Part 2: Maximum Observed Plasma Concentration (Cmax) of Maraviroc
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Maximum Observed Plasma Concentration (Cmax) of Maraviroc | 633.6 ng/mL | Geometric Coefficient of Variation 37 |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Maximum Observed Plasma Concentration (Cmax) of Maraviroc | 432.9 ng/mL | Geometric Coefficient of Variation 53 |
p-value: 0.050590% CI: [49.81, 93.71]Mixed Models Analysis
Secondary
Part 2: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
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).
Time frame: Baseline up to Day 11
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | 0 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | 0 participants |
Secondary
Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities
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.
Time frame: Baseline up to Day 11
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 participants |
Secondary
Part 2: Number of Participants With Laboratory Abnormalities
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.
Time frame: Baseline up to Day 11
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Number of Participants With Laboratory Abnormalities | 1 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Number of Participants With Laboratory Abnormalities | 3 participants |
Secondary
Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 participants |
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 participants |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
Secondary
Part 2: Plasma Concentration of Maraviroc at 24 Hours Post-dose
Time frame: 24 hours post-dose on Day 10
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Plasma Concentration of Maraviroc at 24 Hours Post-dose | 56.56 ng/mL | Geometric Coefficient of Variation 20 |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Plasma Concentration of Maraviroc at 24 Hours Post-dose | 56.34 ng/mL | Geometric Coefficient of Variation 30 |
p-value: 0.971390% CI: [83.07, 119.45]Mixed Models Analysis
Secondary
Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1- No CYP3A5*1 Alleles | Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc | 3.00 hour |
| Cohort 2- One CYP3A5*1 Allele | Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc | 3.02 hour |