Study of MK-6552 in Participants With Narcolepsy Type 1 (MK-6552-004)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-6552 in participants with Narcolepsy Type 1 (NT1). Part 1 will evaluate safety, tolerability, and PK of MK-6552 after administration of ascending doses in a single day to support a dose level decision for Part 2. Part 2 will investigate the PD of MK-6552 after single-day and multiple-day administration. Participants who complete Part 1 and demonstrate that they are able to tolerate at least one dose level of MK-6552 will participate in Part 2.

Official Title
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A Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Sleep Latency Effects of MK-6552 in Participants With Narcolepsy Type 1

Conditions
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Narcolepsy

Intervention / Treatment
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* Drug: MK-6552
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Has history of or current hypertension 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-6552<br>In Part 1, 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. In Part 2, 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. | Drug: MK-6552<br>* Oral capsule administered according to allocation (Part 1)/randomization (Part 2).<br>|
| Placebo Comparator: Placebo<br>In Part 2, participants will receive multiple days of placebo dosing (7 consecutive days). | Drug: Placebo<br>* In Part 2, participants will receive multiple days of placebo dosing (7 consecutive days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing an Adverse Event (AE) | 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. | Up to approximately 7 weeks | 
| Number of participants discontinuing study intervention due to an Adverse Event (AE) | 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. | Up to approximately 5 weeks | 
| Sleep Onset Latency Measured by the Maintenance of Wakefulness Test (MWT) | 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. | 1 hour after each dose on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Curve of MK-6552 from Time Zero to infinity (AUC0-inf) | Blood samples will be collected at specified intervals for the determination of AUC0-inf. AUC0-inf is defined as the area under the concentration-time curve of MK-6552 from time zero to infinity and will be reported for participants in Part 1. | 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) | Blood samples will be collected at specified intervals for the determination of AUC0-24. AUC0-24 is defined as the area under the concentration-time curve of MK-6552 from time zero to 24 hours postdose and will be reported for participants in Part 1. | 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 | Blood samples will be collected at specified intervals for the determination of Tmax. Tmax is defined as the time to the maximum concentration of MK-6552 reached and will be reported for participants in Part 1. | 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 | 
| Maximum Concentration (Cmax) of MK-6552 | Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-6552 reached and will be reported for participants in Part 1. | 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) | Blood samples will be collected at specified intervals for the determination of C2h. C2h is defined as the concentration of MK-6552 reached at 2 hours postdose and will be reported for participants in Part 1. | Day 1: 2 hours postdose | 
| Concentration of MK-6522 at 6 Hours Postdose (C6h) | Blood samples will be collected at specified intervals for the determination of C6h. C6h is defined as the concentration of MK-6552 reached at 6 hours post Dose 1 and will be reported for participants in Part 1. | Day 1: 6 hours post Dose 1 | 
| Concentration of MK-6522 at 18 Hours Postdose (C18h) | Blood samples will be collected at specified intervals for the determination of C18h. C18h is defined as the concentration of MK-6552 reached at 18 hours post Dose 2 and will be reported for participants in Part 1. | 18 hours post Day 1 Dose 2 | 
| Apparent Oral Clearance (CL/F) of MK-6552 | Blood samples will be collected at specified intervals for the determination of CL/F. CL/F is defined as the rate at which MK-6552 is completely removed from plasma and will be reported for participants in Part 1. | 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 | Blood samples will be collected at specified intervals for the determination of Vz/F. Vz/F is defined as the theoretical volume that would be necessary to contain the total amount of administered MK-6522 at the same concentration that it is observed in the blood plasma, and will be reported for participants in Part 1. | 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 Terminal Half-life (t½) of MK-6552 | Blood samples will be collected at specified intervals for the determination of t½. t½ is defined as the time required to divide the MK-6552 plasma concentration by two after reaching pseudo-equilibrium, and will be reported for participants in Part 1. | 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 |