A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3502970 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 133
- 试验地点
- 1
- 主要终点
- Parts A and B: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug
研究概览
简要总结
The main purposes of this study are to determine:
- The safety of LY3502970 and any side effects that might be associated with it.
- How much LY3502970 gets into the bloodstream and how long it takes the body to get rid of it.
This study has 5 parts (A, B, C, D, and E). Parts A and D involve a single dose of LY3502970 and will last about 15 days. Part B and E involve multiple doses of LY3502970 and will last about 4 weeks. Part C involves two single doses of LY3502970 and will last about 29 days. Each participant will enroll in only one part. Screening must be completed within 28 days before study start. This study is for research purposes only, and is not intended to treat any medical condition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
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
- •Healthy male or females, as determined by medical history
- •Have safety laboratory results within normal reference ranges
排除标准
- •Have known allergies to LY3502970, glucagon-like peptide-1 (GLP-1) analogs, related compounds
- •Abnormal electrocardiogram (ECG) at screening
- •Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neurological disorders.
研究组 & 干预措施
Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort J)
Participants received oral doses of LY3502970 once daily for 4 weeks, where 2 mg was given on first week, 5 mg on second week, 12 mg on third week and 24 mg on fourth week. On day 27, midazolam 200 microgram (mcg) was coadministered with 24 mg LY3502970, and 40 mg atorvastatin administered 4 hours after midazolam.
干预措施: Atorvastatin (Drug)
Part B: 2 / 4 / 8 / 16 mg LY3502970 (Cohort I)
Participants received oral doses of LY3502970 once daily for 4 weeks where 2 mg was given for first week, 4 mg for second week, 8 mg for third week and 16 mg for fourth week.
干预措施: LY3502970 (Drug)
Part A 3 mg LY3502970
Participants received a single oral dose of 3 mg LY3502970.
干预措施: LY3502970 (Drug)
Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort K)
Participants received oral doses of LY3502970 once daily for 4 weeks, where 2 mg was given on first week, 5 mg on second week, 12 mg on third week and 24 mg on fourth week. On day 27, 20 mg simvastatin was coadministered with 24 mg LY3502970.
干预措施: Simvastatin (Drug)
Part C: 3 mg LY3502970 (Fed/Fasted)
Part C of the study is exploratory, conducted to study exploratory objectives.
Participants received a single oral dose of 3 mg LY3502970 in treatment period1 (fed condition), followed by administration in treatment period 2 (fasted condition), with a washout period of at least 5 days between periods.
干预措施: LY3502970 (Drug)
Part A 6 mg LY3502970
Participants received a single oral dose of 6 mg LY3502970.
干预措施: LY3502970 (Drug)
Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort K)
Participants received oral doses of LY3502970 once daily for 4 weeks, where 2 mg was given on first week, 5 mg on second week, 12 mg on third week and 24 mg on fourth week. On day 27, 20 mg simvastatin was coadministered with 24 mg LY3502970.
干预措施: LY3502970 (Drug)
Part B Placebo
Participants received oral doses of placebo once daily for 4 weeks.
干预措施: Placebo (Drug)
Part A Placebo
Participants received a single oral dose of Placebo.
干预措施: Placebo (Drug)
Part D: Placebo Prototype Formulation
Part D of the study is exploratory, conducted to study exploratory objectives.
Participants received a single oral dose of placebo in a controlled-release prototype formulation.
干预措施: Placebo (Drug)
Part B: 2 mg LY3502970 (Cohort G)
Participants received oral doses of 2 mg LY3502970 once daily for 4 weeks.
干预措施: LY3502970 (Drug)
Part B: 2 / 4 / 6 mg LY3502970 (Cohort H)
Participants received oral doses of LY3502970 once daily for 4 weeks where 2 mg was given for first week, 4 mg for second week followed by 6 mg on the third and fourth week.
干预措施: LY3502970 (Drug)
Part A 0.3 mg LY3502970
Participants received a single oral dose of 0.3 milligram (mg) LY3502970.
干预措施: LY3502970 (Drug)
Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort J)
Participants received oral doses of LY3502970 once daily for 4 weeks, where 2 mg was given on first week, 5 mg on second week, 12 mg on third week and 24 mg on fourth week. On day 27, midazolam 200 microgram (mcg) was coadministered with 24 mg LY3502970, and 40 mg atorvastatin administered 4 hours after midazolam.
干预措施: LY3502970 (Drug)
Part B: 2 / 5 / 12 / 24 mg LY3502970 (Cohort J)
Participants received oral doses of LY3502970 once daily for 4 weeks, where 2 mg was given on first week, 5 mg on second week, 12 mg on third week and 24 mg on fourth week. On day 27, midazolam 200 microgram (mcg) was coadministered with 24 mg LY3502970, and 40 mg atorvastatin administered 4 hours after midazolam.
干预措施: Midazolam (Drug)
Part E: 2 / 5 / 12 / 24 mg LY3502970 (24 mg as Formulation 1)
Part E of the study is exploratory, conducted to study exploratory objectives.
Participants received oral doses of LY3502970 once daily for 4 weeks where 2 mg was given for first week, 5 mg for second week, 12 mg for third week and 24 mg as formulation 1 for the fourth week.
干预措施: LY3502970 (Drug)
Part A 1 mg LY3502970
Participants received a single oral dose of 1 mg LY3502970.
干预措施: LY3502970 (Drug)
Part D: 3 mg LY3502970 Prototype Formulation
Part D of the study is exploratory, conducted to study exploratory objectives.
Participants received a single oral dose of 3 mg LY3502970 in a controlled-release prototype formulation.
干预措施: LY3502970 (Drug)
Part C: 3 mg LY3502970 (Fasted/Fed)
Part C of the study is exploratory, conducted to study exploratory objectives.
Participants received a single oral dose of 3 mg LY3502970 in treatment period 1 (fasted condition), followed by administration in treatment period 2 (fed condition), with a washout period of at least 5 days between periods.
干预措施: LY3502970 (Drug)
Part E: 2 / 5 / 12 / 24 mg LY3502970 (24 mg as Formulation 2)
Part E of the study is exploratory, conducted to study exploratory objectives.
Participants received oral doses of LY3502970 once daily for 4 weeks where 2 mg was given for first week, 5 mg for second week, 12 mg for third week and 24 mg as formulation 2 for the fourth week.
干预措施: LY3502970 (Drug)
结局指标
主要结局
Parts A and B: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug
时间窗: Baseline through Follow-up (up to Day 42)
An SAE is any adverse event from this study that results in 1 of the following: Death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent 1 of the other outcomes listed in the definition above. The number of participants with one or more SAEs considered by the investigator to be related to study drug administration is reported. An overall summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.
次要结局
- Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3502970(Pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post-dose)
- Part A: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-tlast]) of LY3502970(Pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post-dose)
- Part A: PK: Time of Maximum Observed Concentration (Tmax) of LY3502970(Pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post-dose)
- Part B: PK: Maximum Observed Concentration (Cmax) of LY3502970 on Day 1(Day 1 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24 hours post-dose))
- Part B: PK: Maximum Observed Concentration (Cmax) of LY3502970 on Day 28(Day 28 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 96, 168, 336 hours post-dose))
- Part B: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-tlast]) of LY3502970 on Day 1(Day 1 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24 hours post-dose))
- Part B: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC[0-tlast]) of LY3502970 on Day 28(Day 28 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 96, 168, 336 hours post-dose))
- Part B: PK: Time of Maximum Observed Concentration (Tmax) of LY3502970 on Day 1(Day 1 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24 hours post-dose))
- Part B: PK: Time of Maximum Observed Concentration (Tmax) of LY3502970 on Day 28(Day 28 (pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 96, 168, 336 hours post-dose))