A Pharmacokinetic, Pharmacodynamic, and Drug-Drug Interaction Study of Evacetrapib With Selected Statins in Healthy Chinese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Pharmacokinetics (PK): Area Under Curve (AUC 0-inf) of Evacetrapib
研究概览
简要总结
The main purpose of this study is to investigate how the body responds to evacetrapib and to evaluate the safety and the effect of evacetrapib, alone and in combination with selected statins, in healthy Chinese participants. The study has 2 parts. Part one will last up to 4 weeks and part two will last up to 5 weeks, not including screening. Participants may only enroll in one part.
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
- •Are native Chinese and living in China.
- •Are overtly healthy males or females as determined by medical history and physical examination.
- •Female participants:
- •Women not of child-bearing potential
- •Women of child-bearing potential must correctly use 2 forms of reliable contraception to avoid getting pregnant during the study and for 3 months after the study is completed.
- •Body Mass Index: 19.0 to 24.0 kilogram per square meter (kg/m^2)
- •BP and pulse rate at both supine and standing positions of approximately a systolic BP ≤ 140 millimeter of mercury (mm Hg), and diastolic BP ≤ 90 mm Hg
- •Participants with untreated hypercholesterolemia may be included if not on an herbal or other traditional Chinese medicines (TCM)
- •Have no known liver disease
- •Have given written informed consent
排除标准
- •Are currently enrolled in a clinical trial involving an investigational product (IP) or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
- •Have known allergies to evacetrapib, simvastatin, or atorvastatin, related compounds or any components of the formulation
- •Have previously completed or withdrawn from this study or any other study investigating evacetrapib, and have previously received the IP within 3 months.
- •Have a history within the last year or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurologic disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.
- •Show evidence of significant active neuropsychiatric disease.
- •Regularly use known drugs of abuse
- •Are women with a positive pregnancy test or women who are lactating.
- •Have used or intend to use over-the-counter or prescription medications (including vitamins/mineral supplements) or TCM 14 days prior to the first dose and during the study.
- •Hormonal contraceptives are permitted.
- •Use of any drugs or substances that are known to be substrates, inducers, or inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1), or of any other transporters involved in simvastatin or atorvastatin disposition, or of any drugs or substances that are known to be strong inducers or inhibitors of cytochrome P450 3A (CYP3A) within 30 days prior to the first dose and throughout the study.
- •Donated blood of >400 mL within the last month.
- •Drink alcoholic beverages with intake that exceeds 28 units per week (males) and 21 units per week (females), or are unwilling to stop alcohol consumption 48 hours prior to dosing until discharge from the clinical research unit (CRU) (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
- •Are unwilling to comply with the dietary requirements/restrictions during the study
研究组 & 干预措施
Evacetrapib Single
Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib.
干预措施: Evacetrapib (Drug)
Evacetrapib Multiple
Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib for 14 days.
干预措施: Evacetrapib (Drug)
Simvastatin
Part 2, Cohorts B, Participants will receive simvastatin orally, once daily on Days 1 - 4.
干预措施: Simvastatin (Drug)
Evacetrapib and Simvastatin
Part 2, Cohorts B, Participants will receive evacetrapib orally once daily on Days 5 - 14 and simvastatin orally, once daily on Days 15 - 22.
干预措施: Evacetrapib (Drug)
Evacetrapib and Simvastatin
Part 2, Cohorts B, Participants will receive evacetrapib orally once daily on Days 5 - 14 and simvastatin orally, once daily on Days 15 - 22.
干预措施: Simvastatin (Drug)
Atorvastatin
Part 2, Cohorts C, Participants will receive atorvastatin orally, once daily on Days 1 - 4.
干预措施: Atorvastatin (Drug)
Evacetrapib and Atorvastatin
Part 2, Cohorts C, Participants will receive evacetrapib orally once daily on Days 5 - 14 and atorvastatin orally, once daily on Days 15 - 22.
干预措施: Evacetrapib (Drug)
Evacetrapib and Atorvastatin
Part 2, Cohorts C, Participants will receive evacetrapib orally once daily on Days 5 - 14 and atorvastatin orally, once daily on Days 15 - 22.
干预措施: Atorvastatin (Drug)
结局指标
主要结局
Pharmacokinetics (PK): Area Under Curve (AUC 0-inf) of Evacetrapib
时间窗: Part 1: Day 1 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 hours Postdose
Pharmacokinetic (PK) parameter estimates from evacetrapib concentrations following single dose and daily dose of 130 mg evacetrapib.
PK: Maximum Concentration (Cmax) of Evacetrapib
时间窗: Part 1: Day 1 and Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14: Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours Postdose
Pharmacokinetic parameter estimates from evacetrapib following single dose and daily doses of 130 mg.
PK: Time to Maximum Concentration (Tmax) of Evacetrapib
时间窗: Part 1: Day 1 Predose on Day 1 or Day 14 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours postdose. Part 2: Predose on Day 14 at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose.
Pharmacokinetic parameter estimates of evacetrapib following single and daily doses of 130 mg evacetrapib.
PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin
时间窗: Part 2: Day 14 and 22 Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours Postdose
Pharmacokinetic parameter estimates of evacetrapib following 130 mg evacetrapib daily alone or with 40 mg simvastatin or 20 mg atorvastatin daily AUC (0-24).
PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin
时间窗: Part 2: Day 14 and 22 Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours Postdose.
Pharmacokinetic parameter estimates of evacetrapib following 130 mg evacetrapib daily alone or with 40 mg simvastatin or 20 mg atorvastatin daily.
PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin
时间窗: Part 2: Predose on Day 14 and 22 and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose.
Pharmacokinetic parameter estimates of Tmax of evacetrapib following 130 mg daily dose alone or with 40 mg Simvastatin or 20 mg Atorvastatin. Tmax of simvastatin and atorvastatin.
次要结局
- Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG)(Single Dose Day 2 and Multiple Dose Day 22)