A Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of LY3127760 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
The main purposes of this study are to evaluate the safety and how well the body handles single and multiple doses of increasing strength of study drug, LY3127760. This study includes three parts. Part 3 may be initiated at sponsor's discretion, based on data from Part 2. Participants will only enroll in 1 of the 3 study parts. This study will last approximately 7 to 13 weeks, depending on part. Screening must be completed within 28 days prior to enrollment.
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
- •Overtly healthy males or females as determined by medical history and physical examination
- •Male participants agree to use a reliable method of birth control during the study and 3 months following the last dose of the investigational product
- •Female participants not of child-bearing potential
- •Have a body mass index of 18.5 to 32 kilograms per square meter (kg/m^2) inclusive
- •Are normotensive (defined as supine systolic blood pressure [BP] less than 140 millimeters of mercury [mm Hg] and diastolic BP less than 90 mm Hg) without use of any antihypertensives
排除标准
- •Have known allergies to LY3127760, related compounds or any components of the formulation, celecoxib or sulfonamides, or history of significant atopy. Participants with known aspirin allergy or allergic reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) should also be excluded
- •Have any current or prior history of a significant gastrointestinal illness such as peptic ulcer disease, gastrointestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease or chronic diarrhea
- •Have evidence of other chronic liver disease, including but not limited to chronic alcoholic disease, nonalcoholic steatohepatitis, recent history (within 3 months of screening) of acute viral hepatitis or chronic autoimmune hepatitis
- •Have used any NSAIDs, celecoxib, aspirin or acetaminophen (at doses greater than 1 gram per day), anticoagulants or antiplatelet agents within 14 days of admission
- •Part 2 and Part 3 only
- •Have 1 plus pretrial pitting edema or 2 plus ankle or pedal edema
研究组 & 干预措施
LY3127760 (Single)
Single oral dose of up to 900 milligram (mg) LY3127760 administered in up to 3 of 3 study periods.
干预措施: LY3127760 (Drug)
LY3127760 (Single)
Single oral dose of up to 900 milligram (mg) LY3127760 administered in up to 3 of 3 study periods.
干预措施: Placebo (Drug)
Placebo (Single)
Single oral dose of placebo administered in up to 2 of 3 study periods. Placebo matches LY3127760 in appearance.
干预措施: LY3127760 (Drug)
Placebo (Single)
Single oral dose of placebo administered in up to 2 of 3 study periods. Placebo matches LY3127760 in appearance.
干预措施: Placebo (Drug)
LY3127760 (Multiple)
Multiple ascending oral doses of up to 900 mg LY3127760 administered once or twice daily (QD or BID) for 28 days.
干预措施: LY3127760 (Drug)
LY3127760 (Multiple)
Multiple ascending oral doses of up to 900 mg LY3127760 administered once or twice daily (QD or BID) for 28 days.
干预措施: Placebo (Drug)
Placebo (Multiple)
Multiple oral doses of placebo administered QD or BID for 28 days. Placebo matches LY3127760 in appearance.
干预措施: LY3127760 (Drug)
Placebo (Multiple)
Multiple oral doses of placebo administered QD or BID for 28 days. Placebo matches LY3127760 in appearance.
干预措施: Placebo (Drug)
Celecoxib (Multiple)
Multiple oral doses of 400 mg celecoxib administered QD for 28 days.
干预措施: LY3127760 (Drug)
Celecoxib (Multiple)
Multiple oral doses of 400 mg celecoxib administered QD for 28 days.
干预措施: Celecoxib (Drug)
Celecoxib (Multiple)
Multiple oral doses of 400 mg celecoxib administered QD for 28 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline to Study Completion (Up To Day 42)
Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.
次要结局
- PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC-tau (τ)] of Multiple Doses LY3127760(Day 28: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 Hours)
- PK: Time of Maximum Observed Concentration (Tmax) of Single Dose LY3127760(Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours)
- Pharmacokinetics (PK): Area Under the Concentration Curve Versus Time Curve From Zero to Infinity (AUC 0-∞) of Single Dose LY3127760(Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours)
- PK: Maximum Observed Concentration (Cmax) of Single Dose LY3127760(Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours)
- PK: Tmax of Multiple Doses LY3127760(Post-last dose on Day 28: 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 72, and 168 Hours)
- PK: Cmax of Multiple Doses LY3127760(Post last dose on Day 28: 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 72, and 168 Hours)