A Phase 1, Randomized, Investigator- and Participant-Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Characterize the Safety, Tolerability, and Pharmacokinetics of LY4515100 in Healthy Participants and an Open-Label Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics, Safety, and Tolerability of LY4515100 and of LY4515100 on the Pharmacokinetics of CYP and Transporter Substrates in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 123
- 试验地点
- 1
- 主要终点
- Number of participants with one or more serious adverse event(s) (SAEs) of LY4515100 in Parts A and B
研究概览
简要总结
The main purpose of this study is to assess the safety and tolerability of LY4515100 when given orally to healthy participants. LY4515100 will be given by itself or with other medicines. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. The study will have 3 parts and will last about 50 days. For each participant in Part A, the study will include a stay in the Clinical Research Unit (CRU) lasting about 6 days. For each participant in Part B, the study will include a stay in the CRU lasting about 15 days. For each participant in Part C, the study will include up to 2 stays in the CRU each lasting between 7-28 days.
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 C is 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
- •Are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs, and cardiac monitoring.
- •Have a body mass index within the range of 18.5 to 32.0 kilograms per square meter (kg/m²) (inclusive).
- •Individuals not of childbearing potential (INOCBP) may participate in this trial.
排除标准
- •Have donated 500 milliliters (mL) of blood within 30 days prior to dosing.
- •Have participated within the last 30 days in a clinical study involving an investigational medicinal product. If the previous investigational product (IP) has a long half-life, 5 half-lives or 30 days (whichever is longer) should have passed.
- •Participants with hemoglobin outside of the local laboratory normal reference range for age and sex, which is judged to be clinically significant by the investigator.
- •Participants with an estimated glomerular filtration rate <90 mL/min/1.73 m².
- •Have a 12-lead Electrocardiogram (ECG) abnormality that, in the opinion of the investigator,
- •increases the risks associated with participating in the study
- •may confound ECG data analysis
- •Have used or intend to use over-the-counter or prescription medication including dietary or herbal medications within 7 days, or 14 days if the medication is a potential enzyme inducer, or 5 half-lives (whichever is longer), prior to dosing.
- •Smoke more than 10 cigarettes per day or the equivalent, including electronic cigarettes, and are unable to abide by investigative site smoking restrictions.
- •Have an average weekly alcohol intake that exceeds 14 units per week (males 65 years of age or younger) and 7 units per week (females and males greater than 65 years of age, if applicable)
- •Show evidence of
- •Human immunodeficiency virus (HIV) infection and/or positive human HIV antigen and/or antibodies
- •hepatitis C and/or positive hepatitis C antibody
- •hepatitis B and/or positive hepatitis B surface antigen.
- •Have liver disease.
- •Any clinical condition or procedure (for example, gastrointestinal obstruction, gastric bypass, or cholecystectomy) that may affect the absorption, distribution, or excretion of the study drug and confound pharmacokinetics (PK) assessment.
- •Part C Only:
- •Have history of neuropathy of any cause.
- •Have impaired hearing or a history of hearing problems.
- •Have any medical conditions, medical history, or are taking any medications that are contraindicated in the itraconazole prescribing information, such as prior history of hypersensitivity to itraconazole or other azoles.
- •Participants with any known history of thyroid disease
研究组 & 干预措施
LY4515100 and Transporter Substrates or Renal Marker of Part C
LY4515100 and Transporter Substrates or Renal Marker will be given either orally or intravenously (IV)
干预措施: Rosuvastatin (Drug)
Placebo Part A
Placebo will be given orally
干预措施: Placebo (Drug)
Placebo Part B
Placebo will be given orally
干预措施: Placebo (Drug)
LY4515100 and Itraconazole of Part C
LY4515100 and Itraconazole will be given orally
干预措施: LY4515100 (Drug)
LY4515100 and Metformin of Part C
LY4515100 and Metformin will be given orally
干预措施: LY4515100 (Drug)
LY4515100 and Transporter Substrates or Renal Marker of Part C
LY4515100 and Transporter Substrates or Renal Marker will be given either orally or intravenously (IV)
干预措施: LY4515100 (Drug)
LY4515100 and Metformin of Part C
LY4515100 and Metformin will be given orally
干预措施: Metformin (Drug)
LY4515100 and Transporter Substrates or Renal Marker of Part C
LY4515100 and Transporter Substrates or Renal Marker will be given either orally or intravenously (IV)
干预措施: Iohexol (Drug)
LY4515100 and Transporter Substrates or Renal Marker of Part C
LY4515100 and Transporter Substrates or Renal Marker will be given either orally or intravenously (IV)
干预措施: Digoxin (Drug)
LY4515100 and Transporter Substrates or Renal Marker of Part C
LY4515100 and Transporter Substrates or Renal Marker will be given either orally or intravenously (IV)
干预措施: Caffeine (Drug)
LY4515100 and Itraconazole of Part C
LY4515100 and Itraconazole will be given orally
干预措施: Itraconazole (Drug)
LY4515100 of Part A (SAD)
Single-ascending doses of LY4515100 will be given orally
干预措施: LY4515100 via SAD (Drug)
LY4515100 of Part B (MAD)
Multiple-ascending doses of LY4515100 will be given orally
干预措施: LY4515100 via MAD (Drug)
结局指标
主要结局
Number of participants with one or more serious adverse event(s) (SAEs) of LY4515100 in Parts A and B
时间窗: Day 1 up to Day 30
SAEs of LY4515100
Number of participants with one or more serious adverse event(s) (SAEs) of LY4515100
时间窗: Day 1 up to Day 30
SAEs of LY4515100
次要结局
- PK: Maximum Observed Drug Concentration (Cmax) of LY4515100(Day 1 through Day 11)
- PK: Geometric Means of Area Under the Concentration-Time Curve From 0 to Infinity [AUC(0-∞)] of LY4515100 in Combination with Itraconazole versus LY4515100 Alone(Day 1 through Day 50)
- PK: Geometric Means of Cmax of LY4515100 in Combination with Itraconazole versus LY4515100 Alone(Day 1 through Day 50)
- PK: Geometric Means of AUC(0-∞) of Substrate in Combination with LY4515100 versus Substrate Alone(Day 1 through Day 36)
- PK: Geometric Means of Cmax of Substrate in Combination with LY4515100 versus Substrate Alone(Day 1 through Day 36)
- Pharmacokinetics (PK): Area Under the Concentration versus Time Curve (AUC) of LY4515100(Day 1 through Day 11)
- PK: Maximum Observed Drug Concentration (Cmax) of LY4515100(Time Frame: Day 1 through Day 11)
- PK: Time of maximum observed drug concentration (tmax) of LY4515100(Day 1 through Day 11)