Clinical trial NCT06179407: Study of MK-6552 in Participants With Narcolepsy Type 1 (MK-6552-004)
Official title: A Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Sleep Latency Effects of MK-6552 in Participants With Narcolepsy Type 1
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Narcolepsy
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-12-21
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants experiencing an Adverse Event (AE)
timeFrame: Up to approximately 9 weeks
measure: Number of participants discontinuing study intervention due to an Adverse Event (AE)
timeFrame: Up to approximately 7 weeks
measure: Sleep Onset Latency Measured by the Maintenance of Wakefulness Test (MWT)
timeFrame: 1 hour after each dose on Day 7
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve of MK-6552 from Time Zero to infinity (AUC0-inf)
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve of MK-6552 from Time Zero to 24 hours postdose (AUC0-24)
timeFrame: 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
measure: Time to Maximum Concentration (Tmax) of MK-6552
timeFrame: 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
measure: Maximum Concentration (Cmax) of MK-6552
timeFrame: 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
measure: Concentration of MK-6522 at 2 Hours Postdose (C2h)
timeFrame: Day 1: 2 hours postdose
measure: Concentration of MK-6522 at 6 Hours Postdose (C6h)
timeFrame: Day 1: 6 hours post Dose 1
measure: Concentration of MK-6522 at 18 Hours Postdose (C18h)
timeFrame: 18 hours post Day 1 Dose 2
measure: Apparent Oral Clearance (CL/F) of MK-6552
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of MK-6552
timeFrame: 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
measure: Apparent Terminal Half-life (t½) of MK-6552
timeFrame: 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
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Delta Waves, Inc. ( Site 0008)
state: Colorado
city: Brandon
country: United States
facility: Teradan Clinical Trials, LLC ( Site 0005)
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc ( Site 0006)
state: Georgia
city: Columbia
country: United States
facility: Bogan Sleep Consultants ( Site 0001)
state: South Carolina
city: Austin
country: United States
facility: FutureSearch Trials of Neurology ( Site 0004)
state: Texas
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: