- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT01447511
Pharmacogenetics of Warfarin Induction and Inhibition
This research study will help determine how a person's genetic makeup affects their response to drugs, the ability of the body to break down drugs, and their potential to experience an interaction between drugs. The investigators are investigating the drug interactions with the commonly used anticoagulant drug called warfarin. Warfarin is used for the treatment and prevention of life-threatening abnormal blood clots such as deep vein thrombosis, heart attacks, and strokes. The investigators chose warfarin for this study because it is a commonly used drug and must be monitored closely to avoid side effects. The investigators are interested in studying whether individuals with certain genetic profiles react differently to warfarin when it is combined with other drugs. This research is being done to see if certain genetic profiles require us to adjust warfarin doses differently than is needed for the general population. Genetic profiles of subjects are determined from their participation in the Pharmacogenetics Registry study (investigator Richard Brundage, University of Minnesota).
The study hypothesis is: Functionally defective CYP2C9 alleles attenuate the warfarin-fluconazole inhibitory interaction and exacerbate the warfarin-rifampin inductive interaction.
연구 개요
상태
정황
상세 설명
The research question is: How does CYP2C9 genotype modify warfarin drug interactions?
People differ in their genetic makeup. This includes differences in genes involved in drug metabolism, transport, and effect in the body. People with certain genetic profiles produce altered enzymes, transporters, and receptors that may respond in different ways to drugs. Altered enzymes cause some drugs to be broken down at a different rate than normal. As a result, drug concentrations build up in the blood, and increase the risk of side effects. Furthermore, when two drugs are taken together, the possibility exists for the drugs to interact, with one drug causing a change in the metabolism of the other or both of the drugs. It is not known whether people with an altered genetic makeup also have an altered experience with drug interactions. Altered drug transporters can affect the absorption and elimination of drugs as compared to normal causing differences in how long the drug stays in the body. Finally, altered drug receptors can respond differently to drugs and, thus, produce altered desired or undesired effects.
In this study, the investigators will be investigating the drug interactions with the commonly used anticoagulant drug warfarin in subjects with five different CYP2C9 genotypes. The CYP2C9 genotype is particularly important because this drug metabolizing enzyme governs the metabolic clearance of the more potent chemical entity (the S-enantiomer) of the drug. Warfarin is used for the treatment and prevention of life-threatening abnormal blood clots such as deep vein thrombosis, myocardial infarction, and strokes. The investigators chose warfarin for this study because it is a commonly used drug and must be monitored closely to avoid side effects. The investigators are interested in studying whether individuals with certain genetic alleles of the CYP2C9 genotype react differently to warfarin when it is combined with an antifungal (fluconazole) that inhibits CYP2C9-mediated metabolism and an antibiotic (rifampin) that induces CYP2C9-mediated metabolism. This research is being done to see if certain genetic profiles require us to adjust warfarin doses differently than is needed for the general population.
The study hypothesis is: Functionally defective CYP2C9 alleles attenuate the warfarin-fluconazole inhibitory interaction and exacerbate the warfarin-rifampin inductive interaction.
연구 유형
등록 (실제)
단계
- 해당 없음
연락처 및 위치
연구 장소
-
-
Minnesota
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Minneapolis, Minnesota, 미국, 55414
- Clinical and Translational Science Institute
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Subjects will be 18-60 years old.
- Women of child bearing age must be willing to use measures to avoid conception during the study period.
- Subjects must agree not to take any known substrates, inhibitors, inducers or activators of either CYP2C9 or CYP3A4 from 1 week prior to the start of each study through the last day of study.
Exclusion Criteria:
- Current cigarette smoker
- Abnormal renal, liver function tests, physical exam, or recent history of hepatic, renal, gastrointestinal or neoplastic disease.
- Allergy to warfarin, fluconazole or rifampin and other chemically related drugs.
- Recent ingestion (< 1 week) of any medication known to be metabolized by or alter CYP2C9 or CYP3A4 activity.
- A positive pregnancy test at the time of the pharmacokinetic study.
- Lab tests indicative of abnormal blood clotting capacity.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
---|---|
다른: CYP2C9*1/*1 Genotype
This genotype is considered the wild type genotype.
Individuals with the CYP2C9*1/*1 genotype have two *1 alleles and participated in the following interventions: Control - Warfarin only, Fluconazole - Warfarin, and Rifampin - Warfarin.
|
A single 10 mg warfarin dose taken at the start of the study period.
No other medications taken during this study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
400 mg fluconazole taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
300 mg rifampin taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
|
다른: CYP2C9*1B/*1B Haplotype
Individuals with the CYP2C9*1B/*1B haplotype have two CYP2C9*1B alleles and participated in the following interventions: Control - Warfarin only and Rifampin - Warfarin.
|
A single 10 mg warfarin dose taken at the start of the study period.
No other medications taken during this study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
300 mg rifampin taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
|
다른: CYP2C9*1/*3 Genotype
Individuals with the CYP2C9*1/*3 genotype have one *1 allele and one *3 allele and participated in the following interventions: Control - Warfarin only, Fluconazole - Warfarin, and Rifampin - Warfarin.
|
A single 10 mg warfarin dose taken at the start of the study period.
No other medications taken during this study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
400 mg fluconazole taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
300 mg rifampin taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
|
다른: CYP2C9*2/*3 Genotype
Individuals with the CYP2C9*2/*3 genotype have one *2 and one *3 allele and participated in the following interventions: Control - Warfarin only, Fluconazole - Warfarin, and Rifampin - Warfarin.
|
A single 10 mg warfarin dose taken at the start of the study period.
No other medications taken during this study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
400 mg fluconazole taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
300 mg rifampin taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
|
다른: CYP2C9*3/*3 Genotype
Individuals with the CYP2C9*3/*3 genotype have two *3 alleles and participated in the following interventions: Control - Warfarin only, Fluconazole - Warfarin, and Rifampin - Warfarin.
|
A single 10 mg warfarin dose taken at the start of the study period.
No other medications taken during this study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
400 mg fluconazole taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
A single 10 mg warfarin dose taken at the start of the study period.
300 mg rifampin taken every morning starting a week before the start of the study period and continuing throughout the study period.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Warfarin Clearance.
기간: Over three (two for CYP2C9*1B/*1B participants) 12-16 day study periods.
|
Warfarin enantiomer (S-warfarin and R-warfarin) clearance was measured in healthy volunteers genotyped for CYP2C9*1/*1, CYP2C9*1B/*1B, CYP2C9*1/*3, CYP2C9*2/*3 and CYP2C9*3/*3 to determine the magnitude of the warfarin-fluconazole (inhibition) and warfarin-rifampin (induction) drug interactions.
|
Over three (two for CYP2C9*1B/*1B participants) 12-16 day study periods.
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Richard Brundage, PhD, University of Minnesota
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 약물의 생리적 효과
- 약리작용의 분자기전
- 항감염제
- 핵산 합성 억제제
- 효소 억제제
- 호르몬, 호르몬 대체물 및 호르몬 길항제
- 항균제
- 시토크롬 P-450 효소 억제제
- 나병 치료제
- 호르몬 길항제
- 시토크롬 P-450 효소 유도제
- 항진균제
- 항응고제
- 스테로이드 합성 억제제
- 시토크롬 P-450 CYP3A 유도제
- 항결핵제
- 14-알파 데메틸라제 억제제
- 항생제, 항결핵
- 사이토크롬 P-450 CYP2B6 유도제
- 사이토크롬 P-450 CYP2C8 유도제
- 사이토크롬 P-450 CYP2C19 유도제
- 사이토크롬 P-450 CYP2C9 유도제
- 시토크롬 P-450 CYP2C9 억제제
- 시토크롬 P-450 CYP2C19 억제제
- 리팜핀
- 와파린
- 플루코나졸
기타 연구 ID 번호
- 0807M38361
- P01GM032165-26 (미국 NIH 보조금/계약)
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. .
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