Narcolepsy
Conditions
Brief summary
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.
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).
Interventions
DRUGMK-6552
Oral capsule
DRUGPlacebo
Oral capsule matched to MK-6552
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing an Adverse Event (AE) | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | The AUC0-∞ of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| 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 | The AUC0-24 of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| 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 | The Cmax of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| 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 | The Tmax of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| Concentration of MK-6522 at 2 Hours Postdose (C2h) | Day 1 Dose 1: 2 hours postdose. Day 1 Dose 2: 2 hours postdose. | The C2h of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| Concentration of MK-6522 at 6 Hours Postdose (C6h) | Day 1 Dose 1: 6 hours postdose | The C6h of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| Concentration of MK-6522 at 18 Hours Postdose (C18h) | Day 1 Dose 2: 18 hours postdose | The C18h of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| 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 | The CL/F of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| 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 | The Vz/F of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
| 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 | The apparent t½ of MK-6554 was determined for arms receiving 2 oral doses spaced 6 hours apart. |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Adult participants with narcolepsy type 1 were enrolled at 5 study sites in the United States.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.7 years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 9 | 2 / 8 | 1 / 7 | 1 / 7 | 2 / 6 | 0 / 1 | 1 / 7 |
| other Total, other adverse events | 3 / 9 | 2 / 8 | 1 / 7 | 1 / 7 | 2 / 6 | 0 / 1 | 1 / 7 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 1 | 0 / 7 |
Outcome results
None listed