- ICH GCP
- USA klinikai vizsgálatok nyilvántartása
- Klinikai vizsgálat NCT02625207
THE EFFECT OF CYP3A5 GENOTYPE ON THE PHARMACOKINETICS OF MARAVIROC
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
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
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.
Tanulmány típusa
Beiratkozás (Tényleges)
Fázis
- 1. fázis
Kapcsolatok és helyek
Tanulmányi helyek
-
-
Connecticut
-
New Haven, Connecticut, Egyesült Államok, 06511
- Pfizer New Haven Clinical Research Unit
-
-
Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
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
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Nem véletlenszerű
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
---|---|
Kísérleti: Cohort 1
African-Americans with No CYP3A5*1 alleles (poor metabolizer)
|
300 mg twice daily x 5 days
Más nevek:
150 mg once daily x 10 days
Más nevek:
800/150 mg once daily x 10 days
Más nevek:
|
Kísérleti: Cohort 2
African-Americans with One CYP3A5*1 allele (intermediate metabolizer)
|
300 mg twice daily x 5 days
Más nevek:
|
Kísérleti: Cohort 3
African-Americans with Two CYP3A5*1 alleles (extensive metabolizer)
|
300 mg twice daily x 5 days
Más nevek:
150 mg once daily x 10 days
Más nevek:
800/150 mg once daily x 10 days
Más nevek:
|
Kísérleti: Cohort 4
Caucasians with No CYP3A5*1 alleles (poor metabolizer)
|
300 mg twice daily x 5 days
Más nevek:
|
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
---|---|---|
Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc
Időkeret: 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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
Part 2: Area Under The Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) of Maraviroc
Időkeret: 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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
|
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)
Időkeret: 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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
---|---|---|
Part 1: Average Plasma Concentration (Cavg) of Maraviroc
Időkeret: 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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
Part 2: Average Plasma Concentration (Cavg) of Maraviroc
Időkeret: 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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
|
Part 1: Maximum Observed Plasma Concentration (Cmax) of Maraviroc
Időkeret: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
|
Part 2: Maximum Observed Plasma Concentration (Cmax) of Maraviroc
Időkeret: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
|
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
Időkeret: 12 hours post-dose on Day 5
|
12 hours post-dose on Day 5
|
|
Part 2: Plasma Concentration of Maraviroc at 24 Hours Post-dose
Időkeret: 24 hours post-dose on Day 10
|
24 hours post-dose on Day 10
|
|
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Maraviroc
Időkeret: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
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
Időkeret: Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10
|
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
Időkeret: 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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
Part 1: Average Plasma Concentration (Cav) of Metabolites of Maraviroc
Időkeret: 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.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5
|
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metabolites of Maraviroc
Időkeret: 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
|
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolites of Maraviroc
Időkeret: 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
|
Part 1: Plasma Concentration of Metabolites of Maraviroc at 12 Hour Post-dose
Időkeret: 12 hour post-dose on Day 5
|
Metabolites of maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573.
|
12 hour post-dose on Day 5
|
Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Időkeret: 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.
|
Baseline up to end of study (up to 6 days)
|
Part 2: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Időkeret: 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.
|
Baseline up to end of study (up to 11 days)
|
Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities
Időkeret: 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.
|
Baseline up to Day 6
|
Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities
Időkeret: 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.
|
Baseline up to Day 11
|
Part 1: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
Időkeret: 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).
|
Baseline up to Day 6
|
Part 2: Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
Időkeret: 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).
|
Baseline up to Day 11
|
Part 1: Number of Participants With Laboratory Abnormalities
Időkeret: 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.
|
Baseline up to Day 6
|
Part 2: Number of Participants With Laboratory Abnormalities
Időkeret: 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.
|
Baseline up to Day 11
|
Együttműködők és nyomozók
Szponzor
Együttműködők
Publikációk és hasznos linkek
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
Elsődleges befejezés (Tényleges)
A tanulmány befejezése (Tényleges)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Becslés)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
- A farmakológiai hatás molekuláris mechanizmusai
- Fertőzésgátló szerek
- Vírusellenes szerek
- Enzim gátlók
- HIV-ellenes szerek
- Retrovirális szerek
- Proteáz inhibitorok
- Citokróm P-450 CYP3A gátlók
- Citokróm P-450 enzimgátlók
- HIV proteáz inhibitorok
- Vírusproteáz gátlók
- HIV fúziós gátlók
- Viral Fusion Protein inhibitorok
- CCR5 receptor antagonisták
- Cobicistat
- Maraviroc
- Darunavir
- Kobicisztát keverék darunavirrel
Egyéb vizsgálati azonosító számok
- A4001110
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .
Klinikai vizsgálatok a Egészséges alanyok
-
ArdelyxBefejezveHealthy Volunteers Food Interaction StudyEgyesült Államok
-
AstraZenecaBefejezveHealthy Volunteers Bioekvivalencia vagy Biohasznosulási tanulmányEgyesült Királyság
-
3MBefejezveBőr (FLACC Scores of Test Subjects) Szalag eltávolítása utánEgyesült Államok
Klinikai vizsgálatok a Maraviroc (Part 1)
-
Virginia Commonwealth UniversityCenters for Disease Control and PreventionJelentkezés meghívóvalErőszak | Serdülőkori viselkedés | Erőszakos eseménynek való kitettségEgyesült Államok
-
Instituto de Salud Carlos IIIMég nincs toborzásEgyüttérzés | Serdülőkori viselkedés | Haláli szorongásSpanyolország
-
Manuel Castillo GarzónBefejezveA fizikai aktivitás | Öregedés
-
International Partnership for Microbicides, Inc.National Institute of Allergy and Infectious Diseases (NIAID); National Institutes...Befejezve
-
Optimer Pharmaceuticals LLCBefejezveHasmenés | Clostridium fertőzésekEgyesült Államok, Franciaország, Egyesült Királyság, Belgium, Spanyolország, Kanada, Németország, Olaszország, Svédország
-
Region SkaneSwedish Council for Working Life and Social ResearchVisszavont
-
Optimer Pharmaceuticals LLCBefejezveClostridium Difficile okozta hasmenés
-
ViiV HealthcarePfizerNem áll rendelkezésre
-
Astellas Pharma Europe Ltd.BefejezveGyulladásos bélbetegség (IBD) | Clostridium Difficile fertőzés (CDI)Ausztria, Franciaország, Görögország, Olaszország, Lengyelország, Orosz Föderáció, Egyesült Királyság
-
Optimer Pharmaceuticals LLCBefejezve