A Phase I, Open-label, Fixed-sequence, Drug Interaction Study to Investigate the Effect of Multiple Oral Doses of Pirtobrutinib (LOXO-305) on the Pharmacokinetics of Repaglinide (CYP2C8 Substrate) in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide
研究概览
简要总结
The main purpose of this study is to evaluate the effect of pirtobrutinib (LOXO-305) on single oral dose of repaglinide (CYP2C8 substrate) when administered as multiple doses by conducting the blood tests to measure how much pirtobrutinib (LOXO-305) is in the bloodstream and how the body handles and eliminates pirtobrutinib (LOXO-305) in adult healthy participants. The study will also evaluate the safety and tolerability of pirtobrutinib (LOXO-305). The study is conducted in two periods. Participants will stay in this study for up to 54 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive
- •Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator
- •Female participants of non-childbearing potential and male participants who follow standard contraceptive methods
- •Must have comply with all study procedures, including the 16-night stay at the Clinical Research Unit (CRU) and follow-up phone call
排除标准
- •History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor
- •Known ongoing alcohol and/or drug abuse within 2 years prior to Screening
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee)
研究组 & 干预措施
Period 2: 200 mg Pirtobrutinib QD
Participants received oral doses of 200 mg pirtobrutinib tablets, once daily (QD) in the morning from Day 2 to Day 11.
干预措施: Pirtobrutinib (Drug)
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
干预措施: Repaglinide (Drug)
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide
Participants received oral doses of 200 mg pirtobrutinib QD and 0.5 mg repaglinide tablets, in the morning on Day 12.
干预措施: Pirtobrutinib (Drug)
Period 1: 0.5 mg Repaglinide
Participants received a single oral dose of 0.5 milligrams (mg) repaglinide tablet, in the morning on Day 1.
干预措施: Repaglinide (Drug)
结局指标
主要结局
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: AUC(0-t) of repaglinide was reported.
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: AUC(0-inf) of repaglinide was reported.
PK: Maximum Observed Concentration (Cmax) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: Cmax of repaglinide was reported.
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: AUC-inf (%extrap) of repaglinide was reported.
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: Tmax of repaglinide was reported.
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: Lambda Z of repaglinide was reported.
PK: Apparent Systemic Clearance (CL/F) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: CL/F of repaglinide was reported.
PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: t½ of repaglinide was reported.
PK: Apparent Volume of Distribution (Vz/F) of Repaglinide
时间窗: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
PK: Vz/F of repaglinide was reported.
PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib
时间窗: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
PK: AUC0-t of pirtobrutinib was reported.
PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib
时间窗: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
PK: AUCtau of pirtobrutinib was reported.
PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib
时间窗: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
PK: Cmax of pirtobrutinib was reported.
PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib
时间窗: Period 2: 24-hour post-dose on Day 12
PK: Ctrough of pirtobrutinib was reported.
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
时间窗: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
PK: Tmax of pirtobrutinib was reported.
PK: Apparent Systemic Clearance (CL/F) at Steady State of Pirtobrutinib
时间窗: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
PK: CL/F at steady state of pirtobrutinib was reported.
次要结局
未报告次要终点