A Study of MK-8189 in Participants With Schizophrenia (MK-8189-014)

Schizophrenia Clinical Trial

Official title:

A Multiple Ascending Dose Clinical Study to Evaluate the Safety, Tolerability, PK and the Effect of MK-8189 on QTc in Participants With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05406440
• Other study ID #: 8189-014
• Secondary ID: MK-8189-014
• Status: Completed
• Phase: Phase 1
• Start date: July 12, 2022
• Est. completion date: February 24, 2023

Study information

• Verified date: February 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to assess the safety and tolerability of multiple ascending doses of MK-8189 in participants with schizophrenia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: February 24, 2023
• Est. primary completion date: February 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria with the onset of the first episode being no less than 2 years prior to screening and monotherapy with antipsychotics for treatment should be indicated.
• Is in the non-acute phase of their illness and clinically stable for 3 months prior to screening as demonstrated by: 1) no clinically significant change in dose of prescribed antipsychotic medication, or clinically significant change in antipsychotic medication to treat symptoms of schizophrenia for two months prior to screening; 2) no increase in level of psychiatric care due to worsening of symptoms of schizophrenia for three months prior to screening.
• Has a history of receiving and tolerating antipsychotic medication within the usual dose range employed for schizophrenia.
• Is able to discontinue the use of all antipsychotic medication at least 5 days or 3 half-lives (whichever is longer) prior to Day -1 and during the study period.

Exclusion Criteria:

• Is at imminent risk of self-harm.
• Has a history of cancer (malignancy). Exceptions: 1) adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix; 2) malignancies which have been successfully treated =10 years prior to the prestudy (screening) visit; 3) highly unlikely to sustain a recurrence for the duration of the study.
• Has evidence or history of a primary DSM-5 axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria within one month of screening.
• Has evidence or history of mental retardation, borderline personality disorder, anxiety disorder, or organic brain syndrome.
• Has a history of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia.
• Has a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse.
• Has a DSM-5 defined substance use disorder (excluding nicotine and caffeine) within 3 months of screening.
• Has a history of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures.
• Has a clinically significant history or presence of sick sinus syndrome, first, second, or third degree atrioventricular (AV) block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged corrected QT (QTc) interval, or conduction abnormalities.
• Meets any of the following cardiac parameters: a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), uncorrected hypokalemia or hypomagnesemia, or is taking concomitant medications that prolong the QT/QTc interval.
• Has history of repeated or frequent syncope, vasovagal episodes, or epileptic seizures.
• Has a family history of cardiac sudden death.
• Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
• Has received or is currently receiving treatment with clozapine for schizophrenia for any length of time or treatment with monoamine oxidase inhibitors within 3 months of screening or cariprazine within 2 months of screening.
• Has received a parenteral depot antipsychotic medication within 3 months of screening.
• Has received any nonlive vaccine starting from 14 days prior to study intervention or is scheduled to receive any nonlive vaccine through 30 days following study intervention.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• MK-8189
MK-8189 4 mg and/or 12 mg tablet(s) will be administered orally QD for a total daily dose of 48 mg, 60 mg, 80 mg.
• Placebo
MK-8189 dose-matching placebo tablets will be administered orally QD.

Locations

Country	Name	City	State
United States	Collaborative Neuroscience Research, LLC ( Site 0004)	Garden Grove	California
United States	California Clinical Trials Medical Group managed by PAREXEL ( Site 0002)	Glendale	California
United States	Hassman Research Institute Marlton Site ( Site 0003)	Marlton	New Jersey

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	Number of participants experiencing an Adverse Event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.	Up to 17 days
Primary	Number of participants discontinuing study treatment 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE will be reported.	Up to 3 days