An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of LOXO-292 on the Single Dose Pharmacokinetics of Repaglinide in Healthy Adult 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
- PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide
研究概览
简要总结
The main purpose of this study is to assess the effect of selpercatinib on how fast repaglinide gets into the blood stream and how long it takes the body to remove it when administered in healthy participants. Information about safety and tolerability will be collected. The study will last up to 12 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
- •Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²) and had a minimum weight of at least 50 kg at screening
- •Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study
- •Hemoglobin (Hb) A1c value < 6.5 % at screening and fasting glucose ≤ 126 mg/dL.
- •Males who are capable of fathering a child must agree to use one of the following methods of contraception from the time of the dose administration through 6 months after the last dose
- •Female of non-childbearing potential only or must have undergone sterilization procedures at least 6months prior to the first dosing
排除标准
- •History or presence of diabetes or history of prior episode(s) of hypoglycemia.
- •Estimated creatinine clearance <90 mL/min at Screening or Check-in (Day -1, Period 1)
- •Unable to refrain from or anticipates the use of any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements for 14 days prior to the first dosing and through EOT or ET. After first dosing, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the PI or designee
研究组 & 干预措施
Period 1: Repaglinide
- Day 1: Participants received single dose of 0.5 mg repaglinide tablet.
干预措施: Repaglinide (Drug)
Period 2: Selpercatinib + Repaglinide
- Day 1 to Day 9: Participants received 160 mg Selpercatinib capsule twice daily (BID).
- Day 10: Participant received 160 mg Selpercatinib capsules BID co-administered with a single oral dose of 0.5 mg Repaglinide tablet on the morning of Day 10.
干预措施: Repaglinide (Drug)
Period 2: Selpercatinib + Repaglinide
- Day 1 to Day 9: Participants received 160 mg Selpercatinib capsule twice daily (BID).
- Day 10: Participant received 160 mg Selpercatinib capsules BID co-administered with a single oral dose of 0.5 mg Repaglinide tablet on the morning of Day 10.
干预措施: Selpercatinib (Drug)
结局指标
主要结局
PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
PK: Maximum Observed Concentration (Cmax) of Repaglinide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Repaglinide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
PK: Time to Reach Maximum Observed Concentration (Tmax) of Repaglinide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
PK: Apparent Terminal Elimination Rate Constant (Kel) of Repaglindide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
PK: Apparent First-order Terminal Elimination Half-life (t½) of Repaglinide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Repaglinide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
PK: CL/F of Repaglinide
PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Repaglinide
时间窗: Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 hours post dose)
次要结局
- PK: Area Under the Concentration-time Curve, From Time 0 to the 12 Hour (AUC0-12) of Selpercatinib(Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib(Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Maximum Observed Concentration (Cmax) of Selpercatinib(Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Time to Reach Maximum Observed Concentration (Tmax) of Selpercatinib(Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Area Under the Concentration-time Curve During a Dosing Interval (Tau) at Steady State (AUCtau) of Selpercatinib(Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Maximum Observed Concentration at Steady-state (Cmax,ss) of Selpertcatinib(Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib(Period 2: Predose at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9)
- PK: Time to Reach Maximum Observed Concentration at Steady-state (Tmax,ss) of Selpercatinib(Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))
- PK: Apparent Total Plasma Clearance at Steady State After Oral/Extravascular Administration (CL,ss/F) of Selpercatinib(Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose))