Evenamide, a Glutamate Release Modulator, as Add-On to Standard of Care in Subjects With Documented Treatment-Resistant Schizophrenia

A Phase III, 12-week, Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center Study to Determine the Efficacy, Safety, and Tolerability of a Dose of 15 mg Bid of Evenamide as add-on in Patients With Documented Treatment-resistant Schizophrenia, Which is Not Adequately Controlled by a Stable Therapeutic Dose of the Patient's Current Antipsychotic Medication(s)

This is a prospective, 12-week, randomized, double-blind, placebo-controlled study, designed to evaluate the efficacy, safety, and tolerability of a dose of evenamide of 15 mg bid, compared to placebo, as add-on treatment in patients with documented treatment-resistant schizophrenia (TRS) who have prospectively demonstrated inadequate response to their current stable therapeutic dose of an antipsychotic(s). Approximately 400 patients will be randomized equally (1:1) to each of the two treatment groups in this study.

Key Inclusion Criteria:

• Age - 18 years, or older.
• If female, the subject has a negative pregnancy test at the screening visit and at baseline, is not lactating, and agrees to use adequate contraception, unless not of childbearing potential.
• Meets current DSM-5-TR criteria for schizophrenia.
• Has shown treatment-resistance to antipsychotics as per TRRIP working group definition (Howes et al., 2017).
• Currently receiving "standard of care" therapy of a minimal recommended therapeutic dose of one or more antipsychotic(s).
• Has a Clinical Global Impression - Severity of disease (CGI-S) rating of "mildly ill" to "among the most extremly ill" at baseline.
• Has a BPRS total score ≥ 45 at screening and baseline.
• Has a PANSS total score ≥ 70 at baseline.
• Has a Global Assessment of Functioning (GAF) scale total score ≤ 50.
• Adherence to prescribed antipsychotic treatment.
• Patient has provided written informed consent prior to participating in the study.

Key Exclusion Criteria:

• Current DSM-5-TR diagnosis of schizophreniform disorder, schizoaffective disorder, or other primary psychiatric diagnosis, such as bipolar disorder or major depressive disorder
• History (within three months of study entry) or current diagnosis of "Substance Use Disorder" as defined by the DSM-5-TR criteria.
• Severity of current episode of psychosis requires that the patient be hospitalized to stabilize the severity of his/her psychotic symptoms. However, these patients may qualify for the study provided their antipsychotic dose has been stable for 6 weeks prior to screening.
• History or current diagnosis of other psychiatric or behavioral disorders.
• Known suicidal risk, or a suicide attempt within the past 2 years.
• History of neuroleptic malignant syndrome or priapism.
• Disease/medical condition of any type that may impact the patient's safety or interfere with any of the study evaluations.
• History or current diagnosis of epilepsy or seizure disorder, or occurrence of a seizure within the past year, or repeated drug-induced seizures.