A Study to Evaluate the Effect of Single and Multiple Doses of MK-1084 on the Single-Dose Pharmacokinetics of Midazolam and Digoxin in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- CL/F of Digoxin
研究概览
简要总结
The goal of the study is to see what happens to levels of midazolam and digoxin in a person's body over time (a pharmacokinetic or PK study). Researchers will compare what happens to midazolam and digoxin in the body when it is given with and without another medicine called calderasib. Researchers are testing if digoxin and midazolam levels in the body are different when digoxin and midazolam are given with or without calderasib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 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
- •The key inclusion criteria include but are not limited to the following:
- •Is medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vitals signs, and electrocardiograms (ECGs)
- •Has a body mass index (BMI) ≥18 and ≤32 kg/m^2, inclusive
排除标准
- •The key exclusion criteria include but are not limited to the following:
- •Has a medical history that may confound the results of the study or poses an additional risk to the participant in the study
- •Has a history or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds
研究组 & 干预措施
Period 1: Midazolam and Digoxin
Participants will receive a single oral dose of midazolam and a single oral dose of digoxin on Day 1.
干预措施: Midazolam (Drug)
Period 1: Midazolam and Digoxin
Participants will receive a single oral dose of midazolam and a single oral dose of digoxin on Day 1.
干预措施: Digoxin (Drug)
Period 2: Calderasib, Midazolam, and Digoxin
A washout period of at least 10 days will occur following midazolam and digoxin dosing in Period 1 and the first calderasib dosing in Period 2. Participants will receive calderasib once daily on Days 1 through Day 15 with a single oral dose of midazolam on Days 1, 6, and 14 and a single oral dose of digoxin on Days 1 and 11.
干预措施: Calderasib (Drug)
Period 2: Calderasib, Midazolam, and Digoxin
A washout period of at least 10 days will occur following midazolam and digoxin dosing in Period 1 and the first calderasib dosing in Period 2. Participants will receive calderasib once daily on Days 1 through Day 15 with a single oral dose of midazolam on Days 1, 6, and 14 and a single oral dose of digoxin on Days 1 and 11.
干预措施: Midazolam (Drug)
Period 2: Calderasib, Midazolam, and Digoxin
A washout period of at least 10 days will occur following midazolam and digoxin dosing in Period 1 and the first calderasib dosing in Period 2. Participants will receive calderasib once daily on Days 1 through Day 15 with a single oral dose of midazolam on Days 1, 6, and 14 and a single oral dose of digoxin on Days 1 and 11.
干预措施: Digoxin (Drug)
结局指标
主要结局
CL/F of Digoxin
时间窗: Predose and at designated timepoints up to 120 hours postdose
Blood samples will be collected to determine the CL/F of digoxin.
Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of Midazolam
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the AUC0-last of midazolam.
Maximum Plasma Concentration (Cmax) of Midazolam
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the Cmax of midazolam.
Area Under the Concentration-Time Curve from Time 0 to 24 hours (AUC0-24hr) of Midazolam
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the AUC0-24hr of midazolam.
Cmax of Digoxin
时间窗: Predose and at designated timepoints up to 120 hours postdose
Blood samples will be collected to determine the Cmax of digoxin.
Vz/F of Digoxin
时间窗: Predose and at designated timepoints up to 120 hours postdose
Blood samples will be collected to determine the Vz/F of digoxin.
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of Midazolam
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the AUC0-inf of midazolam.
t1/2 of Digoxin
时间窗: Predose and at designated timepoints up to 120 hours postdose
Blood samples will be collected to determine the t1/2 of digoxin.
Apparent Clearance (CL/F) of Midazolam
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the CL/F of midazolam.
Tmax of Digoxin
时间窗: Predose and at designated timepoints up to 120 hours postdose
Blood samples will be collected to determine the Tmax of digoxin.
Time to Maximum Plasma Concentration (Tmax) of Midazolam
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the Tmax of midazolam.
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Midazolam
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the Vz/F of midazolam.
AUC0-Last of Digoxin
时间窗: Predose and at designated timepoints up to 120 hours postdose
Blood samples will be collected to determine the AUC0-last of digoxin.
AUC0-24hr of Digoxin
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the AUC0-24hr of digoxin.
Apparent Terminal Half-life (t1/2) of Midazolam
时间窗: Predose and at designated timepoints up to 24 hours postdose
Blood samples will be collected to determine the t1/2 of midazolam.
AUC0-Inf of Digoxin
时间窗: Predose and at designated timepoints up to 120 hours postdose
Blood samples will be collected to determine the AUC0-inf of digoxin.
次要结局
- Number of Participants Who Experience an Adverse Event (AE)(Up to approximately 1 month)
- Fraction of Unchanged Digoxin in Urine (Fe)(Predose and at designated timepoints up to 120 hours postdose)
- Number of Participants Who Discontinue Study Due to an AE(Up to approximately 1 month)
- Amount of Drug Excreted in Urine from Time 1 to Time 2 (Aet1-t2) of Digoxin(Predose and at designated timepoints up to 120 hours postdose)
- Total Amount of Drug Excreted in Urine (Ae) of Digoxin(Predose and at designated timepoints up to 120 hours postdose)
- AUC0-24hr of Calderasib(Predose and at designated timepoints up to 24 hours postdose)
- AUC0-Last of Calderasib(Predose and at designated timepoints up to 24 hours postdose)
- Cmax of Calderasib(Predose and at designated timepoints up to 24 hours postdose)
- C24 of Calderasib(Predose and at designated timepoints up to 24 hours postdose)
- Tmax of Calderasib(Predose and at designated timepoints up to 24 hours postdose)
- t1/2 of Calderasib(Predose and at designated timepoints up to 24 hours postdose)
- Cmax Accumulation Ratio of Calderasib(Predose and at designated timepoints up to 24 hours postdose)
- AUC0-24 Accumulation Ratio of Calderasib(Predose and at designated timepoints up to 24 hours postdose)