An Open-Label, Single-Dose Study to Investigate the Influence of Renal Impairment on the Pharmacokinetics of MK-6482
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to Infinity (AUC0-inf)
研究概览
简要总结
The primary purpose of this study is to compare the plasma pharmacokinetics (PK) of belzutifan (MK-6482) following a single oral 120 mg dose in participants with end stage renal disease (ESRD) before and after hemodialysis (HD) to each other and also to that of healthy matched control participants. This study will also evaluate the safety and tolerability of a single oral 120 mg dose of belzutifan in participants with ESRD and the extent of belzutifan removed by HD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Participants With Healthy Renal Function
- •Is in good health based on the opinion of the investigator.
- •Male participants agree to remain abstinent from heterosexual intercourse on a long-term basis or must agree to use contraception as instructed.
- •Female participants must be of nonchildbearing potential.
- •For Participants With end stage renal disease (ESRD)
- •With exception of the renal impairment, is in good health based on the opinion of the investigator.
- •Has ESRD maintained on stable regimen of at least 3 times per week hemodialysis (HD) for at least 3 months prior to the initial administration of the study intervention.
- •Male participants agree to remain abstinent from heterosexual intercourse on a long-term basis or must agree to use contraception as instructed.
- •Female participants must be of nonchildbearing potential.
排除标准
- •For Participants With Healthy Renal Function
- •Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases.
- •Has a history of cancer (malignancy).
- •Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV).
- •Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
- •Has received any non-live vaccine starting from 14 days prior to study intervention or is scheduled to receive any non-live vaccine through 30 days following study intervention (except coronavirus disease 2019 [COVID-19]).
- •Participants With ESRD
- •Has a history of cancer (malignancy).
- •Has required frequent emergent HD (≥3) within a year prior to the initial dose of study intervention.
- •Is positive for HBsAg, hepatitis C antibodies, or HIV.
- •Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
- •Has received any non-live vaccine starting from 14 days prior to study intervention or is scheduled to receive any non-live vaccine through 30 days following study intervention (except COVID-19)
研究组 & 干预措施
Belzutifan in Healthy Participants
In period 1, healthy participants will receive a single, oral dose of belzutifan 120 mg on Day 1 of a 4-day period.
干预措施: Belzutifan (Drug)
Belzutifan in Participants with ESRD
In period 1, participants with ESRD will receive a single, oral dose of belzutifan 120 mg on Day 1 after HD. In period 2, participants with ESRD will receive a single, oral dose of belzutifan 120 mg on Day 1 before HD. Each period is 4 days.
干预措施: Belzutifan (Drug)
结局指标
主要结局
Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to Infinity (AUC0-inf)
时间窗: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
AUC0-inf was defined as the area under the concentration-time curve of belzutifan from time zero to infinity. Blood samples collected predose and at multiple timepoints postdose were used to determine AUC0-inf of belzutifan in plasma.
Area Under the Plasma Concentration Time Curve of Belzutifan From Hour 0 to 24 (AUC0-24)
时间窗: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, and 24 hours postdose
AUC0-24 was defined as the area under the concentration-time curve of belzutifan from time zero to 24 hours postdose. Blood samples collected predose and at multiple timepoints postdose were used to determine AUC0-24 of belzutifan in plasma.
Maximum Plasma Concentration (Cmax) of Belzutifan
时间窗: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
Cmax is the maximum concentration of belzutifan observed in plasma. Blood samples collected predose and at multiple timepoints postdose were used to determine Cmax of belzutifan in plasma.
Time to Maximum Plasma Concentration (Tmax) of Belzutifan
时间窗: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
Tmax is the amount of time that belzutifan is present at the maximum concentration observed in plasma. Blood samples collected predose and at multiple timepoints postdose were used to determine Tmax of belzutifan in plasma.
Apparent Terminal Half-life (t½) of Plasma Belzutifan
时间窗: Predose, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, and 72 hours postdose
t1/2 is defined as the time required to divide plasma concentration of belzutifan by half. Blood samples collected predose and at multiple timepoints postdose were used to determine the apparent terminal t1/2 of belzutifan in plasma.
次要结局
- Dialysis Clearance of Belzutifan Based on Plasma (CLD, Plasma)(Pre-dialysis, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, and 4 hours post-dialysis on Day 1 of Period 2 (Study Day ~12))
- Percentage of Participants Who Experienced an Adverse Event (AE)(Up to 32 days)
- Percentage of Participants Who Discontinue Study Intervention Due to an AE(Up to 12 days)