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

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

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.

Study Overview

• Status: Terminated
• Conditions: Narcolepsy
• Intervention / Treatment: Drug: MK-6552; Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves, Inc. ( Site 0008)
  • Florida
    • Brandon, Florida, United States, 33511
      • Teradan Clinical Trials, LLC ( Site 0005)
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research Inc ( Site 0006)
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consultants ( Site 0001)
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology ( Site 0004)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: MK-6552; Oral capsule; Drug: Placebo; Oral capsule matched to MK-6552
Experimental: Panel B; Panel B will assess the effects of repeated MK-6552 dosing across a range of doses compared with placebo.	Drug: MK-6552; Oral capsule; Drug: Placebo; Oral capsule matched to MK-6552

What is the study measuring?

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. Events are reported according to dose. The number of participants with ≥1 AE is reported.	Up to ~34 weeks
Number of Participants Discontinuing Study Intervention Due to 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. Events are reported according to dose. The number of participants that discontinued study intervention due to AE(s) is reported.	Up to ~34 weeks
Sleep Onset Latency Measured by the Maintenance of Wakefulness Test (MWT) Following 7 Days of MK-6554 Treatment	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.	1 hour after Dose 1 and Dose 2 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-∞)	The AUC0-∞ of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	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)	The AUC0-24 of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	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	The Cmax of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	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	The Tmax of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	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)	The C2h of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	Day 1 Dose 1: 2 hours postdose. Day 1 Dose 2: 2 hours postdose.
Concentration of MK-6522 at 6 Hours Postdose (C6h)	The C6h of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	Day 1 Dose 1: 6 hours postdose
Concentration of MK-6522 at 18 Hours Postdose (C18h)	The C18h of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	Day 1 Dose 2: 18 hours postdose
Apparent Oral Clearance (CL/F) of MK-6552	The CL/F of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	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	The Vz/F of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	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	The apparent t½ of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart.	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2024
• Primary Completion (Actual): October 23, 2024
• Study Completion (Actual): October 23, 2024

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Actual): December 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Disorders of Excessive Somnolence; Narcolepsy
• Other Study ID Numbers: 6552-004; MK-6554-004 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No