A Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Sleep Latency Effects of MK-6552 in Participants With Narcolepsy Type 1
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 10
- 主要终点
- Number of participants experiencing an Adverse Event (AE)
研究概览
简要总结
The purpose of this study was to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-6552 in participants with Narcolepsy Type 1 (NT1). The effect of single MK-6552 doses were assessed initially under open-label conditions to evaluate the safety, tolerability, and PK of MK-6552. The effect of repeated MK-6552 doses (every 8 hours [q8h] for 7 days) were assessed under double-blind and placebo-controlled conditions.
详细描述
The study was terminated by the Sponsor on 15OCT2024 out of an abundance of caution regarding elevations in liver function tests in 3 participants (all cases were asymptomatic and none met Hy's law for drug-induced liver injury or SAE criteria).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a diagnosis of NT1, including a valid polysomnography within the previous 5 years and a current diagnosis of NT1 for at least 6 months based on criteria established by the International Classification of Sleep Disorders- Third Edition, or Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [American Psychiatric Association 2013]
- •Is positive for HLA-DQB1*06:02 allele supporting a diagnosis of NT1
- •Has a baseline history of unequivocal cataplexy prior to initiation of anti-cataplexy medications
- •Reports a total sleep time of > 6 hours on at least 4 out of 7 nights each week within the 4 weeks prior to screening visit
排除标准
- •Has history of or current hypertension
- •Has underlying cardiovascular or cerebrovascular conditions in which an acute rise in blood pressure would pose a clinical concern, including but nor limited to aneurysms or arteriovenous malformations
- •Has a history of renal or hepatic impairment
- •Has a history of cardiac ischemia or cerebral ischemia including but not limited to history of stroke, transient ischemic attack, or transient global amnesia
- •Based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale, is at imminent risk of self-harm or of harm to others in the opinion of the investigator
- •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
- •History of cancer (malignancy)
- •Has a history of any of the following sleep disorders: obstructive sleep apnea (OSA) defined as an Apnea Hypopnea Index > 15 per hour per the American Academy of Sleep Medicine alternate criteria, primary insomnia (within the past 6 months), circadian rhythm sleep disorder, shift work sleep disorder (within the past 6 months), clinically significant parasomnia at the discretion of the investigator
- •Has a history of seizure disorder, clinically significant head trauma, or past invasive intracranial surgery or clinically significant dementia
- •Positive test(s) for Hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus
研究组 & 干预措施
Panel A
Participants will receive single oral doses of MK-6552 in ascending fashion approximately 6 hours apart for a single day, based on safety and tolerability of the previous dose. Then, participants will receive multiple days of MK-6552 dosing (7 consecutive days) at the highest safe and well tolerated MK-6552 dose determined on an individual basis from Part 1.
干预措施: Placebo (Drug)
Panel B
Panel B will assess the effects of repeated MK-6552 dosing across a range of doses compared with placebo.
干预措施: Placebo (Drug)
Panel A
Participants will receive single oral doses of MK-6552 in ascending fashion approximately 6 hours apart for a single day, based on safety and tolerability of the previous dose. Then, participants will receive multiple days of MK-6552 dosing (7 consecutive days) at the highest safe and well tolerated MK-6552 dose determined on an individual basis from Part 1.
干预措施: MK-6552 (Drug)
Panel B
Panel B will assess the effects of repeated MK-6552 dosing across a range of doses compared with placebo.
干预措施: MK-6552 (Drug)
结局指标
主要结局
Number of participants experiencing an Adverse Event (AE)
时间窗: Up to approximately 9 weeks
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience an AE will be reported.
Number of participants discontinuing study intervention due to an Adverse Event (AE)
时间窗: Up to approximately 7 weeks
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants that discontinue study intervention due to an AE will be reported.
Sleep Onset Latency Measured by the Maintenance of Wakefulness Test (MWT)
时间窗: 1 hour after each dose on Day 7
The MWT is a daytime polysomnographic procedure that measures objectively the ability to remain awake during sleep-inducing circumstances. Sleep onset latency is defined as the first occurrence of sustained sleep (i.e. 3 consecutive 30 second epochs of N1 \[stage 1\] sleep or any single 30 second epoch of N2 \[stage 2\], N3 \[stage 3 and 4 combined\] or REM). The primary outcome measure of sleep onset latency measured by the MWT on Day 7 will be reported.
Number of Participants Experiencing an Adverse Event (AE)
时间窗: Up to ~34 weeks
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Events are reported according to dose. The number of participants with ≥1 AE is reported.
Number of Participants Discontinuing Study Intervention Due to AE
时间窗: Up to ~34 weeks
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Events are reported according to dose. The number of participants that discontinued study intervention due to AE(s) is reported.
Sleep Onset Latency Measured by the Maintenance of Wakefulness Test (MWT) Following 7 Days of MK-6554 Treatment
时间窗: 1 hour after Dose 1 and Dose 2 on Day 7
The MWT is a daytime polysomnographic procedure that measures objectively the ability to remain awake during sleep-inducing circumstances. Sleep onset latency is defined as the first occurrence of sustained sleep (i.e. 3 consecutive 30 second epochs of N1 \[stage 1\] sleep or any single 30 second epoch of N2 \[stage 2\], N3 \[stage 3 and 4 combined\] or REM). The primary outcome measure of sleep onset latency measured by the MWT on Day 7 of daily repeated MK-6552 treatment is reported.
次要结局
- Concentration of MK-6522 at 6 Hours Postdose (C6h)(Day 1: 6 hours post Dose 1)
- Area Under the Plasma Concentration-Time Curve of MK-6552 from Time Zero to infinity (AUC0-inf)(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Area Under the Plasma Concentration-Time Curve of MK-6552 from Time Zero to 24 hours postdose (AUC0-24)(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Time to Maximum Concentration (Tmax) of MK-6552(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Concentration of MK-6522 at 18 Hours Postdose (C18h)(18 hours post Day 1 Dose 2)
- Maximum Concentration (Cmax) of MK-6552(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Concentration of MK-6522 at 2 Hours Postdose (C2h)(Day 1: 2 hours postdose)
- Apparent Terminal Half-life (t½) of MK-6552(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Apparent Oral Clearance (CL/F) of MK-6552(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Apparent Volume of Distribution (Vz/F) of MK-6552(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Area Under the Plasma Concentration-Time Curve of MK-6552 From Time Zero to Infinity (AUC0-∞)(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Concentration of MK-6522 at 18 Hours Postdose (C18h)(Day 1 Dose 2: 18 hours postdose)
- Area Under the Plasma Concentration-Time Curve of MK-6552 From Time Zero to 24 Hours Postdose (AUC0-24)(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose 1. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 18 hours postdose)
- Maximum Concentration (Cmax) of MK-6552(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Time to Maximum Concentration (Tmax) of MK-6552(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)
- Concentration of MK-6522 at 2 Hours Postdose (C2h)(Day 1 Dose 1: 2 hours postdose. Day 1 Dose 2: 2 hours postdose.)
- Concentration of MK-6522 at 6 Hours Postdose (C6h)(Day 1 Dose 1: 6 hours postdose)
- Apparent Terminal Half-life (t½) of MK-6552(Day 1 Dose 1: Predose, 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose. Day 1 Dose 2: 0.25, 0.5, 1, 2, 3, 4, 6, 8, 18, 21 and 24 hours postdose)