An Open-Label, Single-Dose Clinical Study to Evaluate the Pharmacokinetics of MK-0616 in Participants With Varying Degrees of Renal Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 5
- 主要终点
- Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate
研究概览
简要总结
The primary objective of the study is to compare the plasma pharmacokinetics (PK) of enlicitide decanoate following a single 20 mg dose in participants on a background of statin therapy with varying degrees of renal impairment (moderate, severe, end stage renal disease [ESRD]) to those of healthy mean matched control participants on a background of statin therapy. There is no formal hypothesis.
详细描述
Panel C included participants with ESRD. No urine samples could be obtained on Panel C participants and hence no pharmacokinetic (PK) analysis could be performed for Panel C participants as pre-specified in the protocol.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Be in good health with the exception of renal impairment (RI) and hypercholesterolemia for participants in Panels A, B, and C. Participants with RI that have stable, chronic medical or psychiatric conditions, including but not limited to hypertension, hypercholesterolemia, diabetes mellitus, hyper- or hypothyroidism, gout, and chronic anxiety or depression may be included at the discretion of the investigator
- •Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 40 kg/m^2, inclusive
- •Be on a stable dose of any statin therapy defined as: no changes to dose or type of statin therapy for at least 2 months prior to Screening and participant anticipates no changes to statin therapy throughout the study until the poststudy visit
排除标准
- •History or presence of renal artery stenosis
- •Had a functioning renal transplant in the past 5 years and is taking transplant medication
- •Participants in panels A, B and D: Has rapidly fluctuating renal function as determined by historical measurements
- •Has a history gastrointestinal disease which might affect food and drug absorption, as determined by the investigator, or has had gastric bypass or similar surgery
- •History of cancer (malignancy)
- •History of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
- •Has received an anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) small molecule treatment, monoclonal antibody, or short interfering RNA (siRNA) or RNA interference (ie, Inclisiran) within 12 months prior to Screening
- •Participants with RI (Panels A, B, and C): Taking medications to treat chronic medical conditions and/or conditions associated with renal disease, if participant has not been on a stable regimen for at least 1 month (other than statins, which require a stable dose for at least 2 months) prior to administration of the initial dose of study intervention, and/or is unable to withhold the use of the medication(s) within 4 hours prior to and 4 hours after administration of study intervention
- •Participated in another investigational study within 4 weeks prior to the prestudy (screening) visit
- •Consumes greater than 3 servings of alcoholic beverages per day
- •Consumes excessive amounts, defined as greater than 6 servings of caffeinated beverages per day
研究组 & 干预措施
Panel A: Moderate Renal Impairment (RI)
Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1
干预措施: Enlicitide Decanoate (Drug)
Panel B: Severe RI
Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1
干预措施: Enlicitide Decanoate (Drug)
Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD)
Participants receive Enlicitide Decanoate 20 mg tablet orally on Day 1 and Day 16.
干预措施: Enlicitide Decanoate (Drug)
Panel D: Healthy Controls
Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1.
干预措施: Enlicitide Decanoate (Drug)
结局指标
主要结局
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate
时间窗: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
AUC0-inf was a measure of the total amount of drug in the plasma from the dose administration extrapolated to infinity. Blood for plasma samples was collected at pre-specified timepoints to determine the AUC0-inf of enlicitide decanoate for Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C ESRD - enlicitide decanoate pre-hemodialysis and Panel C ESRD - enlicitide decanoate post-hemodialysis to report AUC0-inf. Per protocol, mean AUC0-inf was reported.
AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate
时间窗: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
AUClast was defined as the area under the concentration-time curve of enlicitide decanoate from time zero to last measurable concentration. Blood for plasma samples was collected at pre-specified timepoints to determine the AUClast of enlicitide decanoate in Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C ESRD - enlicitide decanoate pre-hemodialysis and Panel C ESRD - enlicitide decanoate post-hemodialysis to report AUClast. Per protocol, mean AUClast was reported.
Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate
时间窗: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Cmax was defined as the maximum or peak concentration of enlicitide decanoate observed after its administration. Blood for plasma samples was collected at pre-specified time points to determine the Cmax of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Cmax. Per protocol, mean Cmax was reported.
Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate
时间窗: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Tmax was defined as the time required for a study drug to reach maximum concentration in plasma. Blood for plasma samples was collected at pre-specified time points to determine the Tmax of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Tmax. Per protocol, mean Tmax was reported.
Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate
时间窗: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Half-life (t1/2) was defined as the time required for plasma drug concentration of enclitide decanoate to decrease by 50% from peak. Blood for plasma samples was collected at pre-specified time points to determine the t1/2 of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report t1/2. Per protocol, mean t1/2 was reported.
Apparent Clearance (CL/F) of Enlicitide Decanoate
时间窗: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
CL/F was the apparent total clearance of enlicitide decanoate in plasma over time. Blood for plasma samples was collected at pre-specified timepoints to determine the CL/F of enlicitide decanoate for Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report CL/F. Per protocol, mean CL/F was reported.
Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate
时间窗: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Vz/F was the apparent volume of distribution of enlicitide decanoate between the plasma and the rest of the body, after dose, assessed as the total volume of enlicitide decanoate that would need to be uniformly distributed to achieve the desired plasma drug concentration. Blood for plasma samples was collected at pre-specified time points to determine the Vz/F of Enlicitide Decanoate in Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Vz/F. Per protocol, mean Vz/F was reported.
次要结局
- Panel C: Dialysate Clearance (CLd) of Enlicitide Decanoate(Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose)
- Panel C: Dialysate Concentration (Cd) of Enlicitide Decanoate(Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose)
- Panel C: Amount of Enlicitide Decanoate Excreted (AEd) in Dialysate(Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose)
- Panel C: Percentage of Dose (%Dose) of Enlicitide Decanoate Excreted in Dialysate(Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose)
- Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate(Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours postdose)
- Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe)(Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose)
- Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE(Up to approximately 30 days)
- Renal Clearance (CLr) of Enlicitide Decanoate(Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose)
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 30 days)
- Panel C: Number of Participants Who Discontinued From the Study Treatment Due to an AE(Up to approximately 30 days)