A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Subjects With Impaired Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 主要终点
- Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®
研究概览
简要总结
This is a 2-part study of the pharmacokinetics (PK) of MK-7655. In Part I, the PK of a single 125 mg dose of MK-7655 given in combination with 250 mg of PRIMAXIN® (imipenem + cilastatin) will be determined in participants with impaired renal function and matched control participants. In Part II, the potential for renal insufficiency to affect non-renal clearance mechanisms will be investigated.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Panel A Mild Renal Impairment
Participants with an eGFR of >50 to <80 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
干预措施: MK-7655 (Drug)
Panel A Mild Renal Impairment
Participants with an eGFR of >50 to <80 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
干预措施: Imipenem + Cilastatin (Drug)
Panel B Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel A and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
干预措施: MK-7655 (Drug)
Panel B Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel A and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
干预措施: Imipenem + Cilastatin (Drug)
Panel C Moderate Renal Impairment
Participants with an eGFR of 30 to 50 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
干预措施: MK-7655 (Drug)
Panel C Moderate Renal Impairment
Participants with an eGFR of 30 to 50 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
干预措施: Imipenem + Cilastatin (Drug)
Panel D Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel C and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
干预措施: MK-7655 (Drug)
Panel D Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel C and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1.
干预措施: Imipenem + Cilastatin (Drug)
Panel E Severe Renal Impairment
Participants with an eGFR <30 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: MK-7655 (Drug)
Panel E Severe Renal Impairment
Participants with an eGFR <30 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Imipenem + Cilastatin (Drug)
Panel E Severe Renal Impairment
Participants with an eGFR <30 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Caffeine (Drug)
Panel E Severe Renal Impairment
Participants with an eGFR <30 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Midazolam (Drug)
Panel E Severe Renal Impairment
Participants with an eGFR <30 mL/min/1.73 m^2 receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Omeprazole (Drug)
Panel F Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel E and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: MK-7655 (Drug)
Panel F Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel E and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Imipenem + Cilastatin (Drug)
Panel F Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel E and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Caffeine (Drug)
Panel F Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel E and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Midazolam (Drug)
Panel F Healthy Participants
A subset of healthy control participants were matched specifically to participants in Panel E and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Omeprazole (Drug)
Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD)
Participants with ESRD/HD receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV postdialysis (Part 1, Period 1) and predialysis (Part 1, Period 2). In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg predialysis (Part 2, Period 1) and postdialysis (Part 2, Period 2).
干预措施: MK-7655 (Drug)
Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD)
Participants with ESRD/HD receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV postdialysis (Part 1, Period 1) and predialysis (Part 1, Period 2). In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg predialysis (Part 2, Period 1) and postdialysis (Part 2, Period 2).
干预措施: Imipenem + Cilastatin (Drug)
Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD)
Participants with ESRD/HD receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV postdialysis (Part 1, Period 1) and predialysis (Part 1, Period 2). In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg predialysis (Part 2, Period 1) and postdialysis (Part 2, Period 2).
干预措施: Caffeine (Drug)
Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD)
Participants with ESRD/HD receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV postdialysis (Part 1, Period 1) and predialysis (Part 1, Period 2). In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg predialysis (Part 2, Period 1) and postdialysis (Part 2, Period 2).
干预措施: Midazolam (Drug)
Panel G End Stage Renal Disease with Hemodialysis (ESRD/HD)
Participants with ESRD/HD receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV postdialysis (Part 1, Period 1) and predialysis (Part 1, Period 2). In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg predialysis (Part 2, Period 1) and postdialysis (Part 2, Period 2).
干预措施: Omeprazole (Drug)
Panel H Healthy Volunteers
A subset of healthy control participants were matched specifically to participants in Panel G and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: MK-7655 (Drug)
Panel H Healthy Volunteers
A subset of healthy control participants were matched specifically to participants in Panel G and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Imipenem + Cilastatin (Drug)
Panel H Healthy Volunteers
A subset of healthy control participants were matched specifically to participants in Panel G and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Caffeine (Drug)
Panel H Healthy Volunteers
A subset of healthy control participants were matched specifically to participants in Panel G and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Midazolam (Drug)
Panel H Healthy Volunteers
A subset of healthy control participants were matched specifically to participants in Panel G and receive a single dose of MK-7655 125 mg + PRIMAXIN® 250 mg IV in Part 1. In Part 2, participants receive an oral cocktail containing caffeine 200 mg, midazolam 2 mg, and omeprazole 40 mg.
干预措施: Omeprazole (Drug)
结局指标
主要结局
Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®
时间窗: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose
AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity.
Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
时间窗: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose
The extraction coefficient of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating extraction coefficient was: Extraction Coefficient = ABS\[100\*(post-dialyzer concentration - pre-dialyzer concentration) / pre-dialyzer concentration\].
Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
时间窗: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose
The CLD of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating CLD was: CLd = (1-Hct)\*QB\*\[(pre-dialyzer concentration - post-dialyzer concentration) / (pre-dialyzer concentration)\] where QB=350 mL/min and Hct=hematocrit.
次要结局
- Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN®(At 0.5 hours postdose)
- Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN®(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: Ceoi of Imipenem in Combination With MK-7655(At 0.5 hours postdose)
- Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN®(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: Tmax of Imipenem in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: VZpred of Cilastin in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4(Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose)
- Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN®(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN®(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: AUC0-inf of Imipenem in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: CLpred of Imipenem in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: VZpred of Imipenem in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: Apparent t½ of Imipenem in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: AUC0-inf of Cilastin in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: Ceoi of Cilastin in Combination With MK-7655(At 0.5 hours postdose)
- Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2(Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose)
- Part 1: CLpred of Cilastin in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: CLR of Cilastin in Urine(Predose to 24 hours postdose)
- Part 1: Apparent t½ of Cilastin in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs)(Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks))
- Part 1: Tmax of Cilastin in Combination With MK-7655(Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose)
- Part 1: Renal Clearance (CLR) of MK-7655 in Urine(Predose to 24 hours postdose)
- Part 1: CLR of Imipenem in Urine(Predose to 24 hours postdose)
- Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19(Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose)