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

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

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: MK-8189; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Research, LLC ( Site 0004)
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group managed by PAREXEL ( Site 0002)
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute Marlton Site ( Site 0003)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-8189 Panel A; Participants will receive MK-8189 starting at 48 mg on Day 1 and 60 mg on Day 2.	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.
Experimental: MK-8189 Panel A-1; Participants will receive MK-8189 48 mg on Day 1 and 80 mg on Day 2.	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.
Experimental: MK-8189 Panel C; Participants will receive MK-8189 48 mg on Days 1-2 and 80 mg on Day 3 based on safety and tolerability.	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 Comparator: Placebo; Participants will receive MK-8189-matching placebo.	Drug: Placebo; MK-8189 dose-matching placebo tablets will be administered orally QD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Actual): February 24, 2023
• Study Completion (Actual): February 24, 2023

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Actual): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 8189-014; MK-8189-014 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No