An Active-Controlled Early Phase Study of MK-8189 in Adults With Schizophrenia (MK-8189-005)
Condition: Schizophrenia, Acute Episode
MeSH terms: Schizophrenia
Intervention: MK-8189; Risperidone; Placebo matching MK-8189; Placebo matching risperidone
Intervention description: Oral CR tablets (4 mg) administered QD at the following dose strengths: 4 mg (1 tablet); 8 mg (2 tablets); 12 mg (3 tablets); Oral capsules (2 mg) administered QD at the following dose strengths: 2 mg (1 capsule); 4 mg (2 capsules); 6 mg (3 capsules); Oral placebo tablet(s) matching the MK-8189 tablet, administered QD.; Oral placebo capsule(s) matching the risperidone capsule, administered QD.
Intervention MeSH terms: Risperidone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomly assigned to one of three groups in parallel for the duration of the study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: A double-blind/masking technique will be used. MK-8189 and risperidone will be packaged identically relative to their respective matching placebo so that blinding/masking is maintained.
Enrollment: 224.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Schizophrenia, acute episode; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Summary:

      This will be a randomized, placebo-controlled, parallel-group, multi-site, double-blind trial
      of MK-8189 compared with placebo, using Risperidone as an active control. The participants
      will be adult subjects experiencing an acute episode of schizophrenia, according to the
      criteria specified in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed.
      (DSM-5). This study will be up to 7 weeks in duration, with up to 7 site visits for each
      participant. The study will consist of a Screening/tapering period (up to one week long), a
      4-week treatment period, and a 14-day follow-up period. The primary objective will be to
      assess symptoms of schizophrenia at 4 weeks, and to assess safety and tolerability during
      treatment and post-treatment follow-up. The secondary objective will be to assess the
      severity of schizophrenia at 4 weeks. The primary hypothesis is that MK-8189 is superior to
      placebo in reducing the overall symptoms of schizophrenia as assessed by the mean change from
      baseline in the Positive and Negative Syndrome Scale (PANSS) total score after 4 weeks of
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 to 50 years of age at Screening

          -  Male

          -  Female not of reproductive potential (e.g., postmenopausal or has had a hysterectomy),
             or agrees to practice abstinence or use acceptable contraception

          -  Meets the diagnostic criteria for schizophrenia according to the DSM-5 criteria, or
             has a past diagnosis of schizophrenia with the onset of the first episode being >=1
             year prior to study entry, and has illness duration of <=20 years

          -  Is confirmed to be experiencing an acute episode of schizophrenia

          -  Minimum PANSS score >= 80 at Screening

          -  Has a score of >=4 in 3 or more of the following items (delusions, conceptual
             disorganization, hallucinatory behavior, grandiosity, suspiciousness/persecution) in
             the positive subscale of the PANSS at Screening

          -  Has a CGI-S score >= 4 at Screening

          -  Is able to taper off psychotropic medications without significant destabilization or
             increased suicidality

          -  Has responded positively to an antipsychotic medication other than clozapine in a
             prior psychotic episode

          -  Has an identified responsible external contact person who has regular contact (no less
             than once per week) with the participant

        Exclusion Criteria:

          -  Is currently under involuntary commitment because he/she is considered a danger to
             himself/herself or others

          -  Is unwilling to remain hospitalized for the duration of trial treatment

          -  Is currently participating in or has participated in an interventional clinical
             research study <=6 months prior to Screening, or has participated in more than one
             interventional clinical trial research study within 12 months prior to Screening

          -  Is unwilling to allow audio/video taping of the Mini International Neuropsychiatric
             Interview for Schizophrenia and Psychotic Disorders (MINI) and/or PANSS interview at
             Screening and Baseline

          -  Is currently being treated with and benefiting from medications with a moderate or
             strong inhibiting or inducing effect on Cytochrome P450 (CYP) 3A and/or CYP2C9 and/or
             sensitive substrates of CYP2B6

          -  Has a history of malignancy <= 5 years except for adequately treated basal cell or
             squamous cell skin cancer or in situ cervical cancer

          -  Has a body mass index <18.5 or >40 kg/m˄2

          -  Has a history of treatment-resistant schizophrenia

          -  Has a prolactin laboratory value of >= 5 times the upper limit of normal at Screening

          -  Has a known history or clinical evidence of clinically significant hepatic,
             cardiovascular, or renal disease, or of untreated narrow-angle glaucoma- Has ever been
             diagnosed with epilepsy or had any seizure disorder beyond one childhood febrile
             seizure

          -  Has known serological evidence of human immunodeficiency virus (HIV) antibody

          -  Has a history of neuroleptic malignant syndrome

          -  Has a current diagnosis other than schizophrenia, or a comorbid diagnosis primarily
             responsible for current symptoms and functional impairment

          -  Has a known history of borderline personality disorder, antisocial personality
             disorder, or bipolar disorder

          -  Has a known history of traumatic brain injury, or Alzheimer's disease or another form
             of dementia

          -  Currently meets DSM-5 criteria for substance abuse or alcohol use disorder

          -  Is at imminent risk of self-harm or harm to others