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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Schizophrenia

Treatments: Drug: MK-8189; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05406440

8189-014

MK-8189-014 (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 53 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

53 participants in 4 patient groups, including a placebo group

MK-8189 Panel A

Experimental group

Description:

Participants will receive MK-8189 starting at 48 mg on Day 1 and 60 mg on Day 2.

Treatment:

Drug: MK-8189

MK-8189 Panel A-1

Experimental group

Description:

Participants will receive MK-8189 48 mg on Day 1 and 80 mg on Day 2.

Treatment:

Drug: MK-8189

MK-8189 Panel C

Experimental group

Description:

Participants will receive MK-8189 48 mg on Days 1-2 and 80 mg on Day 3 based on safety and tolerability.

Treatment:

Drug: MK-8189

Placebo

Placebo Comparator group

Description:

Participants will receive MK-8189-matching placebo.

Treatment:

Drug: Placebo