MK-8189 Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003)
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: MK-8189; Placebo; Base Monotherapy
Intervention description: MK-8189, oral, 2 mg and/or 10 mg tablets, taken QD for a total daily dose of 2 mg, 4 mg, 8 mg, 10 mg, 12 mg, 14 mg, 16 mg, 20 mg, or 40 mg; Placebo matching oral 2 mg and/or 10 mg MK-8189 tablets, taken QD; For Part 2 only: participants need to be on monotherapy with an atypical antipsychotic medication (eg, Olanzapine, Quetiapine, Paliperidone, Asenapine, Iloperidone, Aripirprazole, Lurasidone, Risperidone [not to exceed daily dose of 6 mg], or Ziprasidone.) The participant should be on a stable and well tolerated treatment regimen for at least 2 months prior to screening. NOTE: Clozapine is not allowed.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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.
    

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