MK-8189 Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003)

This 3-part dose titration study will assess MK-8189 safety, tolerability, pharmacokinetics (PK), and central nervous system activity. Part 1 (Panels A and B) will assess MK-8189 administered as monotherapy in participants with schizophrenia. Part 2 (Panel C) will assess MK-8189 administered as add-on to atypical antipsychotic treatment in participants with schizophrenia. Part 3 (Panel D) will assess monotherapy with MK-8189 in healthy participants, including those of Japanese descent. The primary hypothesis is that there is at least one dose of MK-8189 that is generally safe and well-tolerated which will have the desired PK parameters in participants with schizophrenia.

As specified by Phase 1 protocol-flexible language in the protocol, modifications to the dose or dosing regimen can be made to achieve the scientific goals of the trial objectives and/or ensure appropriate safety of the trial participants. The proposed doses for each Part may be adjusted downward based on evaluation of safety, tolerability, and pharmacokinetic data observed in previous panels.

Eligibility Criteria:
Inclusion Criteria:

INCLUSION CRITERIA FOR SCHIZOPHRENIA PARTICIPANTS

* Male or non-pregnant and non-breast feeding female. If participant is male with a female partner of child-bearing potential, participant must agree to use a medically acceptable method of contraception during the trial and for 120 days after the last dose of trial drug. If their partner is pregnant, males must agree to use a condom
* Body Mass Index (BMI) ≥ 18.5 and ≤ 40 kg/m\^2
* Meet diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria with the onset of the first episode being no less than 2 years prior to study entry
* Be in the non-acute phase of illness and clinically stable for 3 months prior to screening
* History of receiving and tolerating antipsychotic medication within the usual dose range employed for schizophrenia
* 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 comedication during the study
* Has a negative urinary drug screen at screening

INCLUSION CRITERIA FOR HEALTHY PARTICIPANTS

* Male, or non-pregnant and non-breast feeding female of Japanese or non-Japanese descent. If participant is male with a female partner of child-bearing potential, participant must agree to use a medically acceptable method of contraception during the trial and for 120 days after the last dose of trial drug. If their partner is pregnant, males must agree to use a condom
* Body Mass Index (BMI) ≥ 18.5 and ≤ 35 kg/m\^2
* In good health
* Nonsmoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months
* Has a negative urinary drug screen at screening

Exclusion Criteria:

EXCLUSION CRITERIA FOR SCHIZOPHRENIA PARTICIPANTS

* DSM-IV axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder within one month of screening
* Has evidence or history of mental retardation, borderline personality disorder, anxiety disorder, or organic brain syndrome
* History of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia
* 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
* Has a history of cancer (malignancy) with certain exceptions
* Treatment with clozapine for schizophrenia or treatment with monoamine oxidase inhibitors within 3 months of screening
* Received a parenteral depot antipsychotic medication within 3 months of screening
* Participated in another investigational study within 4 weeks, prior to screening

EXCLUSION CRITERIA FOR HEALTHY PARTICIPANTS

* History of clinically significant endocrine, gastrointestinal, cardiovascular (including hypertension, angina, coronary artery disease, valvular disease, heart rate or rhythm abnormalities), hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
* Mentally or legally incapacitated
* History of clinically diagnosed depression, anxiety disorder, or any history of psychiatric disorders having required drug treatment or hospitalization
* History of cancer (malignancy)
* Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies throughout the trial
* Participated in another investigational study within 4 weeks, prior to screening