Efficacy and Safety of Elpipodect (MK-8189) in Participants With an Acute Episode of Schizophrenia (MK-8189-008)

A Phase 2B Randomized, Double-Blind, Placebo- and Active-Controlled Trial of the Efficacy and Safety of MK-8189 in Participants Experiencing an Acute Episode of Schizophrenia

The purpose of this study was to evaluate the efficacy and safety of elpipodect at a range of doses (8 mg, 16 mg, and 24 mg once daily [QD]) in adult participants who have an acute episode of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria. The primary hypotheses were the following: (1) that elpipodect 24 mg is superior to placebo in reducing the Week 6 mean change from baseline in Positive and Negative Syndrome Scale (PANSS) total score, and (2) that elpipodect 16 mg is superior to placebo in reducing the Week 6 mean change from baseline in PANSS total score.

With Amendment 4, enrollment was changed to approximately 500 participants with removal of the elpipodect 8 mg treatment arm. Participants enrolled before Amendment 4 who were assigned to elpipodect 8 mg QD remained on that dose regimen per protocol.

Inclusion Criteria:

The main inclusion criteria include, but are not limited to the following:

• Meet the diagnostic criteria for schizophrenia according to the DSM-5
• Have an illness duration for schizophrenia of at least 1 year
• Be confirmed to be experiencing an acute episode of schizophrenia as evidenced by ALL of the following: (a) onset of the current acute episode is ≤6 weeks before screening (b) current symptoms represent a marked and substantial worsening compared with the participant's usual symptomatic state prior to the current acute episode, and are associated with diminished functional ability (c) in need of increased psychiatric attention to treat worsening acute episode symptoms
• Have a CGI-S score of ≥4 (moderately ill) at screening and baseline
• Have an identified responsible person referred to as the "external contact person" who has agreed to provide information about the participant's location if needed during outpatient portion of the study. The site personnel must consider this identified responsible person a reliable contact person, and the contact person must have regular contact with the participant (defined at screening as direct contact no fewer than 3 times per week), and with the expectation that this frequency of contact would continue (either in person or via other contact method), throughout duration of the study, including the follow-up period)

Exclusion Criteria:

The main exclusion criteria include, but are not limited to the following:

• Has a primary current diagnosis other than schizophrenia or a comorbid diagnosis that is primarily responsible for the current symptoms and functional impairment
• Meets criteria for moderate to severe substance use disorder within past 6 months prior to screening (excluding those related to caffeine or nicotine)
• Has a known history of the following: (a) borderline personality disorder, anti-social personality disorder, or bipolar disorder (b) traumatic brain injury causing ongoing cognitive difficulties, Alzheimer's Disease, or another form of dementia, or any chronic organic disease of the central nervous system (c) intellectual disability of a severity that would impact ability to participate in the study
• Has a current diagnosis of a psychotic disorder other than schizophrenia or a behavioral disturbance thought to be due to substance abuse
• Is or was under involuntary commitment for the acute episode, because the participant is considered a danger to themselves or others
• Has a history of treatment resistance exhibited by any of the following: (a) no or minimal response to at least 2 periods of treatment lasting 6 weeks or longer, with antipsychotic agents at the maximally tolerated dose. Participants who have responded to antipsychotics only when paired with clozapine are considered treatment-resistant (b) history of electroconvulsive therapy (ECT) treatment for treatment-resistant schizophrenia within the past 6 months (c) past or current use of clozapine as single or adjunctive therapy for schizophrenia within the past 3 months
• Is currently participating in or has participated in another clinical study and received an experimental or investigational drug agent within 3 months prior to screening visit of this current study and has participated in no more than 2 studies in the past 2 years