A Study To Evaluate The Effect Of A Supratherapeutic Dose Of MK-8189 On The QTc Interval In Participants With Schizophrenia (MK-8189-019)

Schizophrenia Clinical Trial

— TQT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05893862
• Other study ID #: 8189-019
• Secondary ID: MK-8189-019
• Status: Completed
• Phase: Phase 1
• Start date: June 26, 2023
• Est. completion date: February 22, 2024

Study information

• Verified date: March 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: February 22, 2024
• Est. primary completion date: February 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• MK-8189
Oral Tablet
• Moxifloxacin
Oral Tablet
• Placebo
Oral Tablet

Locations

Country	Name	City	State
United States	California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0003)	Glendale	California
United States	Velocity Clinical Research, Hallandale Beach ( Site 0002)	Hallandale Beach	Florida
United States	Hassman Research Institute Marlton Site ( Site 0001)	Marlton	New Jersey
United States	NRC Research Institute ( Site 0004)	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in QT interval corrected for heart rate (QTc) following MK-8189 treatment	Electrocardiogram data will be obtained using a digital Holter device and the Fridericia correction of the QT interval (QTcF) will be determined. The change from baseline in QTcF will be calculated by subtracting the QTcF value at the timepoint from the QTcF baseline value.	Baseline and up to 3 days
Primary	Number of participants with adverse events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to ~30 days
Primary	Number of participants who discontinue study drug due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to ~16 days
Secondary	Change from baseline in QT interval corrected for heart rate (QTc) following moxifloxacin treatment	Electrocardiogram data will be obtained using a digital Holter device and the Fridericia correction of the QT interval (QTcF) will be determined. The change from baseline in QTcF wil be calculated by subtracting the QTcF value at the timepoint from the QTcF baseline value.	Baseline and up to 3 days
Secondary	Area Under the Plasma Concentration-Time curve From Time 0 to 24 hours (AUC0-24) of MK-8189	AUC0-24 is defined as the area under concentration-time curve from 0 to 24 hours. Blood samples taken at pre-dose and up to 24 hours post-dose will be used to determine the AUC0-24 of MK-8189.	Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24 hours postdose
Secondary	Area Under the Plasma Concentration-Time Curve from Time 0 to last quantifiable concentration (AUC0-last) of MK-8189	AUC0-last is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. Blood samples taken at pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-last of MK-8189.	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose
Secondary	Maximum Concentration (Cmax) of MK-8189	Cmax is defined as the maximum concentration of MK-8189 observed in plasma. Blood samples taken at pre-dose and at multiple timepoints post-dose will be used to determine the Cmax of MK-8189.	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose
Secondary	Concentration of MK-8189 at 24 Hours (C24) post-dose	C24 is defined as the concentration of MK-8189 observed in plasma at 24 hours. Blood samples taken at 24 hours post-dose will be used to determine the C24 of MK-8189.	24 hours post-dose
Secondary	Time to maximum concentration (Tmax) of MK-8189	Tmax is defined as the time to maximum concentration of MK-8189 observed in plasma. Blood samples taken at pre-dose and at multiple timepoints post-dose will be used to determine the Tmax of MK-8189.	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose
Secondary	Apparent Terminal Half-life (t1/2) of MK-8189	t1/2 is defined as the time required to divide the plasma concentration of MK-8189 by half after reaching pseudo-equilibrium. Blood samples taken at pre-dose and at multiple timepoints post-dose will be used to determine the t1/2 of MK-8189.	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose

External Links

•   Merck Clinical Trials Information