Effects of Potent Inhibition of CYP2C8, CYP2J2, and CYP3A4, Using Gemfibrozil, Ketoconazole, and Clarithromycin as Probes, on the Pharmacokinetics of LY2409021 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021
研究概览
简要总结
The purpose of this study is to examine the effect of gemfibrozil, ketoconazole, and clarithromycin on how much LY2409021 is found in the bloodstream and how long the body takes to get rid of it. The study is split into two parts, Part A and Part B. Participants in Part A are divided into two cohorts (groups). Each cohort will participate in two study periods. Period 1 involves a single dose of LY2409021. Period 2 involves either gemfibrozil or ketoconazole given daily for 21 days with LY2409021 given once on Day 4. Part A will last for 51 days and will also involve screening within 27 days of the start of the study. Part B is only open to participants who successfully completed Part A of the study. Participants in Part B will receive clarithromycin given daily for 21 days with LY2409021 given once on Day 4. Part B will last for 29 days and will also involve screening within 27 days of the start of the study.
详细描述
Part B was added to the trial in August 2013, per protocol amendment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants are overtly healthy males or females, as determined by medical history and physical examination
- •Participants have a body mass index (BMI) of 18.0 to 32.0 kilograms per meter squared (kg/m^2), inclusive, at screening
- •Participants have a fasting blood glucose of 54 to 110 milligrams per deciliter (mg/dL) (3.0 to 6.1 micromoles per liter [mmol/L])
排除标准
- •Participants that have a contraindication to use of clarithromycin
- •Participants that have a personal or family history of long QT syndrome
- •Participants with a family history of sudden unexplained death or cardiac death in an immediate family member under 60 years of age
- •Participants with a personal history of unexplained syncope within the last year
- •Participants who have taken drugs or substances known to be an inducer or inhibitor of cytochrome P450 (CYP)3A4 or CYP2C8 or CYP2J2 (for example, St. John's wort, rifampin, ketoconazole, trimethoprim) within 30 days prior to the first dose
研究组 & 干预措施
LY2409021 Only (Part A, Cohort 1)
Part A, Period 1. Participants will receive a single 20-milligram (mg) oral dose of LY2409021 on Day 1.
干预措施: LY2409021 (Drug)
LY2409021+Gemfibrozil (Part A, Cohort 1)
Part A, Period 2. Participants will receive a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants will also receive a single 20-mg oral dose of LY2409021 on Day 4.
干预措施: LY2409021 (Drug)
LY2409021+Gemfibrozil (Part A, Cohort 1)
Part A, Period 2. Participants will receive a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants will also receive a single 20-mg oral dose of LY2409021 on Day 4.
干预措施: Gemfibrozil (Drug)
LY2409021 Only (Part A, Cohort 2)
Part A, Period 1. Participants will receive a single 20-mg oral dose of LY2409021 on Day 1.
干预措施: LY2409021 (Drug)
LY2409021+Ketoconazole (Part A, Cohort 2)
Part A, Period 2. Participants will receive a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
干预措施: LY2409021 (Drug)
LY2409021+Ketoconazole (Part A, Cohort 2)
Part A, Period 2. Participants will receive a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
干预措施: Ketoconazole (Drug)
LY2409021+Clarithromycin (Part B)
Part B. Participants will receive a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
干预措施: LY2409021 (Drug)
LY2409021+Clarithromycin (Part B)
Part B. Participants will receive a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
干预措施: Clarithromycin (Drug)
结局指标
主要结局
Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021
时间窗: Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)
Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021
时间窗: Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)
次要结局
未报告次要终点