Conditions: Schizophrenia
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 55
Healthy volunteers: yes

Brief 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.

Detailed description:
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.

Arms:
arm 1: Participants with schizophrenia will receive monotherapy of MK-8189 in escalating doses starting at 2 mg once daily (QD) up to 40 mg QD, depending on safety and tolerability arm 2: Participants with schizophrenia will receive add-on therapy of MK-8189 in escalating doses starting at 2 mg QD up to 20 mg QD, depending on safety and tolerability arm 3: Participants with schizophrenia will receive add-on therapy of MK-8189 in escalating doses starting at 4 mg QD up to 20 mg QD, depending on safety and tolerability arm 4: Healthy participants will receive monotherapy of MK-8189 in escalating doses starting at 2 mg QD up to 16 mg QD, depending on safety and tolerability arm 5: Participants with schizophrenia will receive dose-matched placebo to MK-8189 monotherapy arm 6: Participants with schizophrenia will receive dose-matched placebo to MK-8189 add-on therapy arm 7: Healthy participants will receive dose-matched placebo to MK-8189 monotherapy

Interventions: intervention 1: MK-8189 intervention 2: Placebo intervention 3: Base Monotherapy
Intervention descriptions: intervention 1: 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 intervention 2: Placebo matching oral 2 mg and/or 10 mg MK-8189 tablets, taken QD intervention 3: 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.

Protocol document: