A Clinical Trial to Study the Effect of a Single Dose of Islatravir (MK-8591) on the Pharmacokinetics of Methadone
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone
研究概览
简要总结
The present study is designed to determine the effect of islatravir (ISL) [MK-8591] on methadone pharmacokinetics (PK). The primary objective is to assess whether ISL impacts the area under the plasma concentration time curve from dosing to 24 hours postdose (AUC0-24) of S-methadone and R-methadone in participants on oral methadone therapy. It is hypothesized that the plasma AUC0-24hr for S- and R-methadone will be similar after methadone alone compared to methadone and ISL 60 mg coadministration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Has a body mass index (BMI) > 18 and ≤ 35 kg/m^2
- •Is in good health based on laboratory safety tests obtained at the screening visit and prior to administration of study drug
- •Is in good health based on medical history, physical examination, vital sign measurements, and electrocardiograms (ECGs) performed prior to randomization.
- •Has a negative human immunodeficiency virus (HIV) antigen/antibody test at screening
- •For male participants, follows contraception guidance consistent with local regulations
- •For female participants:
- •Is not a woman of childbearing potential (WOCBP) or
- •Is a WOCBP and using acceptable contraception or is abstinent
- •Is reliably participating in a methadone maintenance program for at least two (2) months prior to Day 1
- •Agrees to not change their current maintenance methadone dose of 20-200 mg administered as a single daily dose
排除标准
- •Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
- •Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years
- •Has a history of cancer (malignancy)
- •Has a history of significant multiple and/or severe allergies (eg, food, drug, latex) or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or non-prescription drugs or food
- •Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the screening visit
- •With the exception of methadone, is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to the first dose of the 14-day methadone maintenance run-in phase prior to Day 1, throughout the trial, until the AE follow-up call (Day 16)
- •Has participated in another investigational study within 4 weeks (or 5 half-lives) prior to the prestudy (screening) visit.
- •Has a QTc interval >450 msec (males) or >470 msec (females), has a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), has uncorrected hypokalemia or hypomagnesemia, is taking concomitant medications that prolong the QT/QTc interval other than methadone
- •Does not limit smoking to no more than 10 cigarettes per day while in the clinical research unit (CRU)
- •Consumes greater than 3 glasses of alcoholic beverages per day
- •Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
- •With the exception of tetrahydrocannabinol (THC), has a positive screen for drugs with a high potential for abuse such as cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines (with the exception noted in exclusion criteria 7), or opiates/opioids on Day -1
- •Presents any concern by the investigator regarding safe participation in the study or for any other reason the investigator considers the participant inappropriate for participation in the study
研究组 & 干预措施
Methadone + ISL
Methadone-maintained participants (20 to 200 mg [locally-provided] once daily [QD] from Day -14 to Day -1 and Day 10 to Day 15) receive methadone 20 to 200 mg QD on Day 1 to Day 9; ISL 60 mg is co-administered with methadone on Day 2.
干预措施: Islatravir (Drug)
结局指标
主要结局
Dose-Normalized Area Under the Plasma Concentration Time Curve From 0-24 Hours Postdose (AUC0-24) of R-Methadone
时间窗: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
The AUC0-24 of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Dose-Normalized AUC0-24 of S-Methadone
时间窗: Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose
The AUC0-24hr of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
次要结局
- Dose-Normalized Plasma Concentration 24 Hours Postdose (C24) of R-Methadone(Days 1 and 2: 24 hours postdose)
- Dose-Normalized C24 of S-Methadone(Days 1 and 2: 24 hours postdose)
- Dose-Normalized C24 of Total Methadone(Days 1 and 2: 24 hours postdose)
- Time to Maximum Plasma Concentration (Tmax) of R-Methadone(Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose)
- Dose-Normalized Cmax of Total Methadone(Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose)
- Tmax of Total Methadone(Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose)
- Dose-Normalized Maximum Plasma Concentration (Cmax) of R-Methadone(Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose)
- Dose-Normalized Cmax of S-Methadone(Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose)
- Tmax of S-Methadone(Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose)
- Number of Participants With Adverse Events (AEs) Following Methadone + ISL Coadministration(Up to 16 days)
- Dose-Normalized AUC0-24 of Total Methadone(Days 1 and 2: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 16, and 24 hours postdose)
- Number of Participants Discontinuing Study Therapy Due to AEs Following Coadministration of Methadone and ISL(Up to 15 days)