An Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3866 When Administered to Subjects With Moderate and Severe Hepatic Impairment

Merck Sharp & Dohme LLC2 个研究点分布在 1 个国家目标入组 9 人开始时间: 2017年12月19日最近更新: 2019年11月13日

适应症

干预措施

试验速览

阶段: 1 期
状态: 终止
发起方: Merck Sharp & Dohme LLC
入组人数: 9
试验地点: 2
主要终点: Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is an open-label, single-dose, Phase 1 study to evaluate the pharmacokinetics (PK) of intravenous (IV) MK-3866 in participants with moderate and severe hepatic impairment (HI) compared to that of matched healthy participants. The primary purpose of this study is to understand the effect of HI on the plasma PK of MK-3866 in order to guide dosing recommendations for participants with HI. This study will also evaluate the safety and tolerability of MK-3866 in participants with moderate and severe HI.

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

•Body mass index ≥19 & ≤40 kg/m^2
•Continuous non-smoker prior to screening & enrollment
•HI Participants: Baseline health judged to be stable based on medical history (except for the HI condition), physical examination, vital signs, electrocardiograms, & laboratory safety tests
•Healthy control participants: Is medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms
•HI Participants: Diagnosis of chronic (>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) HI with features of cirrhosis
•HI Participants - Panel A (moderate HI) only: score on the Child-Pugh scale from 7 to 9 (moderate HI). At least 3 participants must have a score of 2 or higher on at least one of the laboratory parameters (i.e., albumin, international normalized ratio, and/or bilirubin) on the Child-Pugh scale
•HI Participants - Panel B (severe HI) only: Score on the Child-Pugh scale from 10 to 15 (severe HI)
•Is completely informed of the unknown risks of pregnancy & agrees not to become pregnant or father a child during time in study
•For a female of childbearing potential: is either sexually inactive (abstinent) for 14 days prior to dosing & throughout the study or is using an acceptable birth control method
•Non-vasectomized male: Participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing

排除标准

•Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
•Has a history or presence of clinically significant medical or psychiatric condition or disease (other than HI - Panels A & B) that might confound the results of the study or poses an additional risk to the participant. Remote history of cholecystectomy that is not an active issue may be included.
•Panels A & B: Has a clinically significant history of cancer. Remote history with full cure or limited disease with complete resection (cure) may be included
•Has a history of drug/alcohol abuse within the past 6 months prior to dosing (Panels A & B) or within the past 2 years prior to dosing (Panel C [Healthy controls])
•Panels A & B: Consumes more than 3 glasses of alcoholic beverages (1 glass approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day, within 6 months of screening. Participants that consume 4 glasses of alcoholic beverages/day may be enrolled
•Panels A & B: Consumes excessive amounts, defined as more than 6 servings (1 serving approximately equivalent to 120 mg of caffeine), of coffee, tea, cola, energy-drinks, or other caffeinated beverages/day
•Panels A & B: Has a history of a liver transplant
•Has a history or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds
•Has moderate or severe renal insufficiency (estimated glomerular filtration rate of ≤60 mL/min/1.73 m2 for moderate HI or healthy control participants or ≤50 mL/min/1.73 m2 for severe HI participants)
•Panel C: Has positive macroscopic urine protein at screening (trace protein by dipstick allowed)
•Is a female participant who is pregnant or lactating
•Has positive results for the urine or breath alcohol screen and/or urine drug screen at screening
•Has positive results at screening for human immunodeficiency virus (HIV) (Panels A & B) or for HIV, HBsAg, or hepatitis C virus (HCV) (Panel C)
•Panels A & B: Participants with active HCV infection or hepatitis B virus (HBV) infection. Participants with prior/inactive HCV infection or past HBV infection may be enrolled.
•Is unable to refrain from or anticipates use of any medication or substance prohibited in study
•Has taken amiodarone at any time in their life

研究组 & 干预措施

Moderate Hepatic Impairment (Panel A)

Experimental

Participants with moderate HI (estimated glomerular filtration rate [eGFR] of ≤60mL/min/1.73m^2) receive a single IV dose of MK-3866 (150 mg) on Day 1.

干预措施: MK-3866 (Drug)

Severe Hepatic Impairment (Panel B)

Experimental

Participants with severe HI (eGFR of ≤50 mL/min/1.73m^2) receive a single IV dose of MK-3866 (150 mg) on Day 1.

干预措施: MK-3866 (Drug)

Healthy Matched Controls (Panel C)

Experimental

Healthy participants receive a single IV dose of MK-3866 (150 mg) on Day 1.

干预措施: MK-3866 (Drug)

结局指标

主要结局

Area Under the Concentration-time Curve of MK-3866 From Time 0 to 24 Hours (AUC0-24hr)

时间窗: Predose, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours postdose

AUC0-24 is determined for the period up to 24 hours post-single dose. AUC0-24 is an estimate of total daily plasma exposure from dosing to 24 hours postdose.

Area Under the Concentration-time Curve of MK-3866 From Time 0 to Infinity (AUC0-∞)