A Phase 1, Open-Label Study to Evaluate the Effect of Multiple Doses of GBT440 on the Pharmacokinetics of Probe Substrates for CYP1A2, CYP2C9, CYP2C19, and CYP3A4 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Peak plasma concentration(Cmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma
研究概览
简要总结
The purpose of this study to evaluate the effect of concomitant administration of GBT440 on caffeine (a CYP1A2 probe substrate), S warfarin (a CYP2C9 probe substrate), omeprazole (a CYP2C19 probe substrate), and midazolam (a CYP3A4 probe substrate) plasma concentrations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject is a female of non-childbearing potential or male, who is healthy, nonsmoking, and 18 to 55 years old, inclusive, at screening
- •Male subjects agree to use contraception
- •Willing and able to give written informed consent
排除标准
- •Evidence or history of clinically significant metabolic, allergic, dermatological, hepatic, renal,hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder
- •History of hypersensitivity or allergy to drugs, foods, or other substances
- •History or presence of abnormal electrocardiogram or hypertension
- •History of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction within 1 year of screening
- •Participated in another clinical trial of an investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to Screening
研究组 & 干预措施
Fixed sequence, 2-periods
An open-label, fixed sequence, 2-period drug interaction study Period 1 Treatment A: Single dose of drug cocktail on Day 1 Period 2 Treatment B: GBT440 on Days 1 through 3 and Treatment C: Single dose of drug cocktail on Day 4 and GBT440 on Days 4 through 7
干预措施: GBT440 (Drug)
结局指标
主要结局
Peak plasma concentration(Cmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma
时间窗: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for caffeine, S warfarin, omeprazole, and midazolam
时间窗: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Area under the plasma concentration time curve from time 0 extrapolated to infinity (AUCinf) for caffeine, S warfarin, omeprazole, and midazolam
时间窗: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
次要结局
- Cmax for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- AUCinf for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- t1/2 (Day7) for GBT440 in whole blood and plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- Terminal elimination half-life (t½) for caffeine, S warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- AUCt for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P)for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- Cmax for GBT440 in whole blood and plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- The time that Cmax was observed (tmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- t1/2 for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- tmax for GBT440 in whole blood and plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- AUC from time 0 to 24 hours (AUC0-24) (Days 4 and 7) for GBT440 in whole blood and plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- tmax, for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- Ratio of metabolite to parent AUCinf corrected for molecular weight (AUCinf M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)
- Ratio of metabolite to parent Cmax corrected for molecular weight (Cmax M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma(0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2)