Single- and Multiple-Ascending Dose Study to Evaluate the Safety and Pharmacokinetics of LY3839840 Following Oral Dosing in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and 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 purpose of this first-in-human study to investigate the safety of LY3839840 in single and multiple doses, and how it's processed in the body when given in different amounts.
详细描述
The study will be conducted in five parts (A, B, C, D, and E) and each enrolled participant will receive a single dose (Parts A and C) or multiple dose (Parts B, C and D) of either LY3839840 or placebo. Part E will study midazolam alone and with LY3839840. The study will last up to approximately 7 weeks for parts A, C (single dose cohort), 8 weeks for parts B, D and C (multiple dose cohort), and up to 3 weeks for Part E.
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
- Double (Participant, Investigator)
盲法说明
Part E is non-randomized and open-label
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 men and women. Women may only be included if they are of nonchildbearing potential
- •For Part C:
- •Part C of the study includes Chinese participants only. To qualify, the participants must be considered as native Chinese, defined as all the participant's biological grandparents being of Chinese origin
- •For Part D:
- •Part D of the study includes Japanese participants only. To qualify, the participants must be first-generation Japanese, defined as the participant's biological parents, and all the participant's biological grandparents, being of exclusive Japanese descent, and being born in Japan
- •Participants who are healthy as determined through medical evaluation including medical history, physical examination, laboratory tests, vital signs, and 12-lead (electrocardiogram ECG)
- •Have a body mass index (BMI) of greater than or equal to 18 to less than or equal to 35 kilograms per square meter (kg/m²). For Parts C and D: BMI greater than or equal to 18 to less than or equal to 29 kilograms per square meter (kg/m²)
- •Participants who have laboratory tests within the normal reference range for the population or CRU or have results with acceptable deviations that are judged by the investigator not to be clinically significant
- •Have venous access sufficient to allow for blood sampling
排除标准
- •Have known allergies to LY3839840, related compounds, or any components of the formulation
- •Have a history or presence of multiple or severe allergies, anaphylactic reaction to prescription or nonprescription drugs, or history of significant atopy
- •Have a significant history of or current rheumatologic, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (such as Cushing syndrome, hyperthyroidism, hyperaldosteronism), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational medicinal product; or of interfering with the interpretation of data
- •Have had any significant infections within 3 months prior to the screening visit, or develop any of these infections before the randomization visit.
- •Have received ≥1 live vaccine within 28 days of screening, or intend to during the study, or ≤28 days after the study
- •Had any surgical procedure (except for minor surgery requiring local or no anesthesia and without any complications or sequelae) within 12 weeks prior to screening, or intend to during the study, or ≤28 days after the study
- •Had any malignancy within the past 5 years. Exceptions: successfully treated basal cell skin carcinoma or squamous cell skin carcinoma with no evidence of recurrence or metastatic disease within the past 3 years
- •Have a history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection that, in the opinion of the sponsor or investigator, poses an unacceptable risk to the participant
- •Have used, or intend to use, prescription or nonprescription medication within 14 days prior to dosing (or 5 half-lives - whichever is longer)
- •Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
- •Have participated in a clinical study involving an investigational product within the last 30 days of the final drug administration (or 5 half-lives - whichever is longer)
- •Show evidence of active or latent TB
- •Are females who are lactating or have a positive pregnancy test at screening or Day -1
- •Blood donation of ≥450 mL, or participation in a clinical study that required a blood volume of ≥400 mL since the last study visit within the past 120 days
研究组 & 干预措施
LY3839840 (Part A)
Single ascending dose of LY3839840 administered orally.
干预措施: LY3839840 (Drug)
LY3839840 (Part B) Cohort 1-3
Multiple ascending dose of LY3839840 administered orally.
干预措施: LY3839840 (Drug)
LY3839840 (Part B) Cohort 4
Multiple ascending dose of LY3839840 administered orally.
干预措施: LY3839840 (Drug)
LY3839840 (Part B) Optional Cohort 5
Multiple ascending dose of LY3839840 administered orally pending data from Cohort 4
干预措施: LY3839840 (Drug)
LY3839840 (Part C)
Single and multiple dose of LY3839840 administered orally in Chinese participants.
干预措施: LY3839840 (Drug)
LY3839840 (Part D)
Multiple ascending dose of LY3839840 administered orally in Japanese participants.
干预措施: LY3839840 (Drug)
Placebo (Parts A-D)
Placebo administered orally.
干预措施: Placebo (Drug)
Midazolam (Part E)
Midazolam substrate alone or with LY3839840 administered orally
干预措施: LY3839840 (Drug)
Midazolam (Part E)
Midazolam substrate alone or with LY3839840 administered orally
干预措施: Midazolam (Drug)
结局指标
主要结局
Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration
时间窗: Baseline up to Week 8
A summary of AEs, TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module
次要结局
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3839840(Predose on day 1 up to 14 days post dose)
- PK: Area Under the Concentration Versus Time Curve (AUC) of LY3839840(Predose on day 1 up to 14 days post dose)
- PK: AUC of Midazolam(Predose on day 1 up to 19 days post-dose)
- PK: Cmax of Midazolam(Predose on day 1 up to 19 days post-dose)