A Study to Characterize LY3314814 Pharmacokinetics as a Function of Dosing Duration and to Determine the Effect of LY3314814 on the Pharmacokinetics of CYP3A Substrates in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814
研究概览
简要总结
The purpose of this study is to study the effect of lanabecestat on how the body absorbs and processes 3 other medications, midazolam, simvastatin and donepezil and how these 3 medications affect lanabecestat when they are taken together. This study is in 2 cohorts, Cohort A is approximately 44 days long and Cohort B about 70 days only. The screening visit is required within 30 days prior to the start on the study
详细描述
Astra Zeneca (AZ) registered this trial as sponsor. In July, 2015, sponsorship changed to Eli Lilly and Company (Lilly). In August, 2015, AZ transferred this trial to Lilly's ClinicalTrials.gov account and Lilly updated the record. This trial is not an applicable trial under the Food and Drug Administration Amendments Act of 2007 (FDAAA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Overtly healthy and either sterile or, male and prepared to use an approved method of contraception
- •Have a body mass index (BMI) at screening of 19.0 to 32.0 kilogram per square meter (kg/m^2)
排除标准
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results, or may limit the subject's ability to participate in the study
- •History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
- •History of previous or ongoing psychiatric disease/condition
研究组 & 干预措施
Cohort A
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35;
20 mg simvastatin, single oral dose on Days 2 and 36;
250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37;
50 mg lanabecestat, single oral dose on Day 4;
50 mg lanabecestat, single oral dose, Days 10 to 37
干预措施: Lanabecestat (Drug)
Cohort A
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35;
20 mg simvastatin, single oral dose on Days 2 and 36;
250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37;
50 mg lanabecestat, single oral dose on Day 4;
50 mg lanabecestat, single oral dose, Days 10 to 37
干预措施: Simvastatin (Drug)
Cohort A
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35;
20 mg simvastatin, single oral dose on Days 2 and 36;
250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37;
50 mg lanabecestat, single oral dose on Day 4;
50 mg lanabecestat, single oral dose, Days 10 to 37
干预措施: Midazolam (Drug)
Cohort B
5 mg donepezil, single oral dose on Day 1, Period 1;
50 mg lanabecestat, single oral dose Days 1 to 43, Period 2;
5 mg donepezil, single oral dose on Day 28, Period 2
干预措施: Donepezil (Drug)
Cohort B
5 mg donepezil, single oral dose on Day 1, Period 1;
50 mg lanabecestat, single oral dose Days 1 to 43, Period 2;
5 mg donepezil, single oral dose on Day 28, Period 2
干预措施: Lanabecestat (Drug)
结局指标
主要结局
Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814
时间窗: Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
时间窗: Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A)
PK Profile for Donepezil: AUC(0-∞)
时间窗: Day 1 and 28: predose 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96,120, 216, 288, and 360 hours (Cohort B)
PK Profile for Simvastatin: AUC(0-∞)
时间窗: Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A)
次要结局
- Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration(Cohort A : Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70))
- Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)(Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70))