THE EFFECT OF CYP3A5 GENOTYPE ON THE PHARMACOKINETICS OF MARAVIROC
2017년 3월 1일 업데이트: 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).
연구 개요
상태
완전한
정황
상세 설명
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.
연구 유형
중재적
등록 (실제)
47
단계
- 1단계
연락처 및 위치
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연구 장소
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Connecticut
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New Haven, Connecticut, 미국, 06511
- Pfizer New Haven Clinical Research Unit
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인)
건강한 자원 봉사자를 받아들입니다
예
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Cohort 1
African-Americans with No CYP3A5*1 alleles (poor metabolizer)
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300 mg twice daily x 5 days
다른 이름들:
150 mg once daily x 10 days
다른 이름들:
800/150 mg once daily x 10 days
다른 이름들:
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실험적: Cohort 2
African-Americans with One CYP3A5*1 allele (intermediate metabolizer)
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300 mg twice daily x 5 days
다른 이름들:
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실험적: Cohort 3
African-Americans with Two CYP3A5*1 alleles (extensive metabolizer)
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300 mg twice daily x 5 days
다른 이름들:
150 mg once daily x 10 days
다른 이름들:
800/150 mg once daily x 10 days
다른 이름들:
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실험적: Cohort 4
Caucasians with No CYP3A5*1 alleles (poor metabolizer)
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300 mg twice daily x 5 days
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc
기간: 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
기간: 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)
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Part 1: Average Plasma Concentration (Cavg) of Maraviroc
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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.
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
기간: 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
기간: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours 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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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
기간: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours 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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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
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
스폰서
협력자
간행물 및 유용한 링크
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연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2015년 11월 6일
기본 완료 (실제)
2016년 3월 26일
연구 완료 (실제)
2016년 3월 26일
연구 등록 날짜
최초 제출
2015년 10월 20일
QC 기준을 충족하는 최초 제출
2015년 12월 8일
처음 게시됨 (추정)
2015년 12월 9일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 4월 17일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 3월 1일
마지막으로 확인됨
2017년 3월 1일
추가 정보
이 연구와 관련된 용어
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
Maraviroc (Part 1)에 대한 임상 시험
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International Partnership for Microbicides, Inc.National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health...완전한
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Louisiana State University Health Sciences Center...Millennium Pharmaceuticals, Inc.빼는
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Asociacion para el Estudio de las Enfermedades...완전한
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ViiV HealthcarePfizer더 이상 사용할 수 없음