Clinical trial NCT05893862: A Study To Evaluate The Effect Of A Supratherapeutic Dose Of MK-8189 On The QTc Interval In Participants With Schizophrenia (MK-8189-019)
Official title: A Double-Blind, Cross-Over Placebo-Controlled and Active-Controlled Trial To Evaluate The Effect Of A Supratherapeutic Dose Of MK-8189 On The QTc Interval In Participants With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-06-08
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study to evaluate the effect of a supratherapeutic dose of 80 mg MK-8189 on the QT interval corrected for heart rate (QTc interval) and to assess the safety and tolerability of multiple once-daily doses of MK-8189 in participants with schizophrenia. The effects of 3 treatment sequences 1) MK-8189 (48 mg \[Day 1\] and 80 mg \[Day2\]); 2) standard image placebo (Day 1) and moxifloxacin 400 mg (Day 2); and 3) MK-8189 placebo (Day 1 and Day 2) were assessed with 5-day washout intervening sequence. Participants received all treatments in a counter-balanced order according to 1 of 6 possible treatment sequences.

The primary hypothesis is that the administration of an 80 mg MK-8189 dose on Day 2 does not prolong the QTc interval to a clinically significant degree. Specifically, the true mean difference (MK-8189 - placebo) in QTc change from baseline is less than 10 milliseconds (msec).


Eligibility criteria: Inclusion Criteria:

* Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria.
* Is in the non-acute phase of their illness.
* Has a history of receiving and tolerating antipsychotics medication within the usual dose range employed for schizophrenia.
* Participants with hypothyroidism, diabetes, high blood pressure, chronic respiratory conditions or other medical conditions could be considered if their condition is stable.

Exclusion Criteria:

* History of a primary DSM-5 axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria.
* History of intellectual disability, borderline personality disorder, anxiety disorder, or organic brain syndrome.
* History of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia (TD).
* History of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures.
* History of cancer.
* History or presence of sick sinus syndrome, atrioventricular (AV) block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QTc interval, or conduction abnormalities.
* History of risk factors for Torsades de Pointes (e.g., heart failure/cardiomyopathy or family history of long QT syndrome).
* History of frequent syncope, vasovagal episodes, or epileptic seizures.
* Family history of sudden cardiac death.
* Has a positive test(s) for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV).
* Had major surgery, donated, or lost 1 unit of blood within 4 weeks prior to the pre-study visit.

Primary outcomes:
measure: Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following MK-8189 Treatment
timeFrame: Day 1 (MK-8189 48 mg and placebo) and Day 2 (MK-8189 80 mg and placebo)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to ~30 days after each dose
measure: Number of Participants Discontinuing Study Therapy Due to AE
timeFrame: Up to ~30 days after each dose
Secondary outcomes:
measure: Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following Moxifloxacin Treatment
timeFrame: Day 2
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of MK-8189
timeFrame: Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24 hours postdose
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-8189
timeFrame: Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, and 72 hours postdose
measure: Maximum Concentration (Cmax) of MK-8189
timeFrame: Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose
measure: Concentration of MK-8189 at 24 Hours (C24) Post-dose
timeFrame: Day 1 and Day 2: 24 hours postdose
measure: Apparent Terminal Half-life (t½) of MK-8189
timeFrame: Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose
measure: Time to Maximum Concentration (Tmax) of MK-8189
timeFrame: Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, and 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, and 72 hours postdose
Other outcomes:
Locations:
city: Glendale
country: United States
facility: California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0003)
state: California
city: Orange
country: United States
facility: NRC Research Institute ( Site 0004)
state: California
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach ( Site 0002)
state: Florida
city: Marlton
country: United States
facility: Hassman Research Institute Marlton Site ( Site 0001)
state: New Jersey
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: