THE EFFECT OF CYP3A5 GENOTYPE ON THE PHARMACOKINETICS OF MARAVIROC
2017年3月1日 更新者：ViiV Healthcare
A Phase 1, Open-label, Parallel-group Study To Assess The Effect Of Cyp3a5 Genotype On The Pharmacokinetics Of Maraviroc And Cyp3a5-derived Metabolites With And Without Darunavir/Cobicistat In African-american And Caucasian Healthy Volunteers
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).
研究概览
详细说明
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.
研究类型
介入性
注册 (实际的)
47
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Connecticut
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New Haven、Connecticut、美国、06511
- Pfizer New Haven Clinical Research Unit
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 55年 (成人)
接受健康志愿者
是的
有资格学习的性别
全部
描述
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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Cohort 1
African-Americans with No CYP3A5*1 alleles (poor metabolizer)
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300 mg twice daily x 5 days
其他名称：
150 mg once daily x 10 days
其他名称：
800/150 mg once daily x 10 days
其他名称：
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实验性的：Cohort 2
African-Americans with One CYP3A5*1 allele (intermediate metabolizer)
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300 mg twice daily x 5 days
其他名称：
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实验性的：Cohort 3
African-Americans with Two CYP3A5*1 alleles (extensive metabolizer)
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300 mg twice daily x 5 days
其他名称：
150 mg once daily x 10 days
其他名称：
800/150 mg once daily x 10 days
其他名称：
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实验性的：Cohort 4
Caucasians with No CYP3A5*1 alleles (poor metabolizer)
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300 mg twice daily x 5 days
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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AUC (0-12) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose.
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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Part 2: Area Under The Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
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AUC (0-24) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose.
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
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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)
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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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.
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Part 1: Average Plasma Concentration (Cavg) of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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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.
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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Part 2: Average Plasma Concentration (Cavg) of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
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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.
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
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Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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Part 2: Maximum Observed Plasma Concentration (Cmax) of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
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Part 1: Plasma Concentration of Maraviroc at 12 Hours Post-dose
大体时间：12 hours post-dose on Day 5
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12 hours post-dose on Day 5
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Part 2: Plasma Concentration of Maraviroc at 24 Hours Post-dose
大体时间：24 hours post-dose on Day 10
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24 hours post-dose on Day 10
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Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
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Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Metabolites of Maraviroc
大体时间：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.
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc
大体时间：Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
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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.
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Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
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Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc
大体时间：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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
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Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc
大体时间：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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
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Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose
大体时间：12 hour post-dose on Day 5
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Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
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12 hour post-dose on Day 5
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Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
大体时间：Baseline up to end of study (up to 6 days)
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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.
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Baseline up to end of study (up to 6 days)
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Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
大体时间：Baseline up to end of study (up to 11 days)
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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.
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Baseline up to end of study (up to 11 days)
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Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities
大体时间：Baseline up to Day 6
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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.
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Baseline up to Day 6
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Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities
大体时间：Baseline up to Day 11
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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.
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Baseline up to Day 11
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Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
大体时间：Baseline up to Day 6
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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).
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Baseline up to Day 6
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Part 2: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
大体时间：Baseline up to Day 11
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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).
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Baseline up to Day 11
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Part 1: Number of Participants With Laboratory Abnormalities
大体时间：Baseline up to Day 6
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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.
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Baseline up to Day 6
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Part 2: Number of Participants With Laboratory Abnormalities
大体时间：Baseline up to Day 11
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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.
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Baseline up to Day 11
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2015年11月6日
初级完成 (实际的)
2016年3月26日
研究完成 (实际的)
2016年3月26日
研究注册日期
首次提交
2015年10月20日
首先提交符合 QC 标准的
2015年12月8日
首次发布 (估计)
2015年12月9日
研究记录更新
最后更新发布 (实际的)
2017年4月17日
上次提交的符合 QC 标准的更新
2017年3月1日
最后验证
2017年3月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- A4001110
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
Maraviroc (Part 1)的临床试验
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International Partnership for Microbicides, Inc.National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health...完全的
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ViiV HealthcarePfizer不再可用
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International Partnership for Microbicides, Inc.撤销
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Centre hospitalier de l'Université de Montréal...McGill University Health Centre/Research Institute of the McGill University Health Centre; Université... 和其他合作者完全的
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Fundación Pública Andaluza para la gestión de la...完全的