An Active-Controlled Early Phase Study of Elpipodect (MK-8189) in Adults With Schizophrenia (MK-8189-005)

A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the Efficacy and Safety of MK-8189 Using Risperidone as an Active Control in Subjects Experiencing an Acute Episode of Schizophrenia

This will be a randomized, placebo-controlled, parallel-group, multi-site, double-blind trial of elpipodect 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 elpipodect 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.

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