A Safety, Tolerability, and Pharmacokinetics Study of MK-8189 in Participants With Schizophrenia and in Healthy Participants (MK-8189-007).

Inclusion Criteria

Panels A and D (Healthy Participants)

- Is in good health based on medical history, physical examination, vital sign (VS)
measurements and 12-lead safety electrocardiograms (ECGs) performed prior to
randomization.

- Is in good health based on laboratory safety tests obtained at the screening visit.

- If participant is of Japanese descent, both biological parents and all biological
grandparents must be born in Japan.

Panel B (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy)

- Is able to discontinue the use of all antipsychotic medication at least 5 days prior to
the start of the treatment period and during the study period.

Panels B and C (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / Add-on
Therapy)

- Is in good health based on laboratory safety tests obtained at the screening visit.

- 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: a.) no clinically significant change in dose of
prescribed antipsychotic medication, or clinically significant change in antipsychotic
medication to treat symptoms of schizophrenia for 2 months prior to screening; b.) no
increase in level of psychiatric care due to worsening of symptoms of schizophrenia
for 3 months prior to screening.

- Has a history of receiving and tolerating antipsychotic medication within the usual
dose range employed for schizophrenia.

- Has a stable living situation in which the patient or a contact person can be reached
by the investigator if there is a need for follow up.

- Participants with hypothyroidism, diabetes, high blood pressure, chronic respiratory
conditions or other mild forms of these medical conditions could be considered as
candidates for study enrollment if their condition is stable and the prescribed dose
and regimen of medication is stable for at least 3 months prior to screening and there
are no expected changes in co-medication during the study.

- Has regular bowel movements and, in the opinion of the investigator, no clinically
significant diarrhea or constipation.

Panels A, B, C, and D

- Have a Body Mass Index (BMI) > 18.5 and ≤ 35 kg/m^2, inclusive, and total body weight
of > 50 kg (110 lbs) at the screening visit.

- Have no clinically significant abnormality on the 12-lead safety ECG performed at the
pre-trial (screening) visit and/or prior to randomization.

- Have a normal resting blood pressure and normal resting heart rate in the
semi-recumbent position at the pre-trial (screening) visit and/or prior to
randomization.

- If female: be postmenopausal; surgically sterile; or, if of reproductive potential, be
not pregnant at the prestudy (screening) visit and agree to use (and/or have their
partner use) 2 acceptable methods of birth control beginning at the prestudy
(screening) visit, throughout the study (including washout intervals between treatment
periods/panels) and until 2 weeks after the last dose of study drug in the last
treatment period.

Exclusion Criteria

Panels A and D (Healthy Participants)

- Has a history of clinically diagnosed depression, anxiety disorder, or any history of
psychiatric disorders having required drug treatment or hospitalization. Participants
who have had situational depression more than 5 years before the start of the study
may be enrolled in the study at the discretion of the investigator.

- Has a history of stroke, chronic seizures, or major neurological disorder.

- Has a history of dystonic reaction to antipsychotic, anti-emetic or related
medication.

- 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. Participants must be excluded if they report suicidal ideation
with intent, with or without a plan or method (e.g., positive response to item 4 or 5
in assessment of suicidal ideation on the C-SSRS) in the past 5 years or suicidal
behavior in their lifetime.

- Has a history of clinically significant endocrine, gastrointestinal, cardiovascular,
hematological, hepatic, immunological, renal, respiratory, genitourinary, or major
neurological (including stroke and chronic seizures) abnormalities or diseases.
Participants with a remote history of uncomplicated medical events may be enrolled in
the study at the discretion of the investigator.

- 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 the
discretion of the investigator.

- Is unable to refrain from or anticipates the use of any medication, including
prescription and nonprescription drugs or herbal remedies, beginning approximately 2
weeks (or 5 half-lives) prior to administration of the initial dose of study drug,
throughout the study (including washout intervals between treatment periods), until
the poststudy visit.

- Is a smoker and/or has used nicotine or nicotine-containing products (e.g., nicotine
patch and electronic cigarette) within 3 months of screening.

Panels B and C (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / Add-on
Therapy)

- 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 (TD).

- Has a substance-induced psychotic disorder or behavioral disturbance thought to be due
to substance abuse.

- Has a DSM-5 defined substance abuse or dependence disorder (excluding nicotine and
caffeine) within three 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, malignance, allergic disease or other
chronic and/or degenerative process at screening.

- Is at imminent risk of self-harm, based on clinical interview and responses on the
C-SSRS, 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
method (e.g., positive response to item 4 or 5 in assessment of suicidal ideation on
the C-SSRS) in the past 2 months or suicidal behavior in the past 6 months.

- Has received treatment with clozapine for schizophrenia or treatment with monoamine
oxidase inhibitors within 3 months of screening. For Panel C participants, has
received a total daily dose of risperidone > 6 mg.

- Is unable to refrain from the use of co-medication with a moderate or strong
inhibiting or inducing effect on cytochrome P450 (CYP) 3A (CYP3A) and/or 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 CYP2B6. There may be certain
medications that are permitted

- Has received a parenteral depot antipsychotic medication within 3 months of pre-trial
(screening).

- Has been in incarceration or imprisonment within 3 months prior to screening.

Panels A, B, C, and D

- Has any clinically significant abnormal laboratory, VS, physical examination, or
12-lead safety ECG findings at screening or changes from baseline that may interfere
with the interpretation of PK or safety parameters or, in the opinion of the
investigator, would make the participant inappropriate for entry into this study.

- Is a woman of childbearing potential (WOCBP) who has a positive serum pregnancy test
at the screening visit or a positive urine pregnancy test within 48 hours before the
first dose of study intervention. If the urine test is positive or cannot be confirmed
as negative, a serum pregnancy test will be required.

- Has a history of cancer (malignancy). Exceptions include: (1) Participants with
adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix
may participate in the study; (2) Participants with other malignancies which have been
successfully treated ≥10 years prior to the prestudy (screening) visit where, in the
judgment of both the investigator and treating physician, appropriate follow-up has
revealed no evidence of recurrence from the time of treatment through the time of the
prestudy (screening) visit (except those cancers identified at the beginning of this
exclusion criteria); or (3) Participants, who, in the opinion of the study
investigator, are highly unlikely to sustain a recurrence for the duration of the
study.

- 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.

- 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.

- Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex
allergy), or has had an anaphylactic reaction or significant intolerability (i.e.,
systemic allergic reaction) to prescription or non-prescription drugs or food.

- Has Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV) infection.

- Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4
weeks prior to the prestudy (screening) visit.

- Has participated in another investigational study within 4 weeks (or 5 half-lives,
whichever is greater) prior to the prestudy (screening) visit. The window will be
derived from the date of the last visit in the previous study.

- Has history or presence of risk factors for Torsade de Pointes (e.g., cardiac disease,
heart failure, hypokalaemia or hypomagnesaemia, hypertrophy, cardiomyopathy, or family
history of long QT syndrome). Plasma calcium must be within normal limits at screening
and serum calcium must be within normal limits prior to dosing.

- Is under the age of legal consent.

- 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 (1 serving is
approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks,
or other caffeinated beverages per day.

- Is a regular user of cannabis, any illicit drugs or has a history of drug (including
alcohol) abuse within approximately 3 years. Participants must have a negative urine
drug screen (UDS) prior to randomization.

- 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.