Safety, Tolerability, and Pharmacokinetics Study of MK-8189 in Participants With Schizophrenia and Healthy Participants (MK-8189-011)

Exclusion Criteria

• •Is a WOCBP who has a positive urine pregnancy test within 48 hours before the first dose of study intervention
• •Participants with schizophrenia only: 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 1 month of screening
• •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 1 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 within 3 months of screening
• •Has a history of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures
• •Has an untreated or uncompensated clinically significant renal, endocrine, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cardiovascular, hematological, immunological or cerebrovascular disease, malignancy, allergic disease or other chronic and/or degenerative process at screening
• •Has any clinically significant abnormal laboratory, vital sign (VS), physical examination, or 12-lead safety ECG findings at screening or changes from baseline parameters or, in the opinion of the investigator, would make the participant inappropriate for entry into this study
• •Has a history of cancer with following exceptions: 1) Adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; 2) Other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study, in the opinion of the investigator and with agreement of the Sponsor
• •Has a clinically significant history or presence of sick sinus syndrome, first, second, or third-degree AV block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged corrected QT (QTc) interval, or conduction abnormalities
• •Has history of repeated or frequent syncope, vasovagal episodes, or epileptic seizures
• •Has a family history of sudden death
• •Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study
• •For Part 2 participants only: Participant has an estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 based on the modification of diet in renal disease (MDRD). Participants who have an eGFR or measured creatinine clearance of up to10% below of either 60 milliliter/minute \[mL/min\] (for creatinine clearance) or 60 mL/min/1.73m2 (for eGFR) may be enrolled in the study at the discretion of the investigator
• •Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• •Is positive for Hepatitis B surface antigen, Hepatitis C antibodies or HIV
• •Had major surgery, donated or lost 1 unit of blood within 4 weeks prior to the prestudy (screening) visit
• •Healthy participants only: Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years (participants who have had situational depression may be enrolled in the study at investigator's discretion)
• •Participants with schizophrenia only: Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator
• •Healthy participants only: Is at imminent risk of self-harm, based on clinical interview and responses on the CSSRS, or of harm to others in the opinion of the investigator. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or in the past 5 years or suicidal behavior in their lifetime
• •Has received treatment with clozapine for schizophrenia 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
• •Is unable to refrain from the use of co-medication with a moderate or strong inhibiting or inducing effect on cytochrome (CYP3A) and/or cytochrome (CYP2C9) beginning approximately 2 weeks or 5 half-lives, whichever is longer, prior to administration of the initial dose of trial drug and throughout the trial or is unable to refrain from the use of sensitive substrates of cytochrome (CYP2B6)
• •Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit
• •Has been in incarceration or imprisonment within three months prior to screening
• •Is a current smoker (healthy participants only) or is a smoker (participants with schizophrenia only) that does not agree to follow the smoking restrictions as defined by the clinical research unit (CRU)
• •Consumes greater than 3 glasses of alcoholic beverages per day. Participants who consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator
• •Consumes excessive amounts, defined as greater than 6 servings of caffeinated beverages per day
• •Is a regular user of cannabis, any illicit drugs or has a history of drug abuse within approximately 3 years
• •Presents any concern by the investigator regarding safe participation in the study or for any other reason the investigator considers the participant inappropriate for participation in the study
• •Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study