Evenamide added to standard antipsychotic treatment for 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)

Phase 3 Interventional Newron Pharmaceuticals SPA · NCT07184619

This 12-week randomized, double-blind test will see if adding evenamide (15 mg twice daily) to a patient’s current antipsychotic helps adults with treatment-resistant schizophrenia improve symptoms compared with placebo.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment400 (estimated)
Ages18 Years and up
SexAll
SponsorNewron Pharmaceuticals SPA Industry-sponsored
Locations5 sites (Los Angeles, California and 4 other locations)
Trial IDNCT07184619 on ClinicalTrials.gov

What this trial studies

In this phase 3, double-blind, placebo-controlled trial, about 400 adults with documented treatment-resistant schizophrenia who remain symptomatic on stable antipsychotic therapy are randomized 1:1 to receive evenamide 15 mg twice daily or placebo for 12 weeks as an add-on. The study measures symptom change, safety, and tolerability using standardized scales and clinician ratings. Key enrollment requirements include DSM-5-TR schizophrenia, prior inadequate response per the TRRIP definition, and minimum baseline thresholds on PANSS and BPRS. Participants must remain on their prescribed antipsychotic regimen and provide informed consent.

Who should consider this trial

Good fit: Adults aged 18 or older with documented treatment-resistant schizophrenia who remain symptomatic despite an adequate, stable antipsychotic regimen and who meet the study’s baseline severity and assessment criteria are the ideal candidates.

Not a fit: Patients who are not adherent to their antipsychotic treatment, who do not meet the trial’s TRS or symptom-severity criteria, who are pregnant or lactating, or who have contraindications to the study drug are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, evenamide could provide an additional medication option to reduce symptoms and improve functioning for people with treatment-resistant schizophrenia.

How similar studies have performed: Earlier-phase and smaller trials of evenamide and similar glutamate-modulating approaches have shown preliminary positive signals, but confirmatory large-scale evidence remains limited.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Los Angeles, California and 4 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Treatment-resistant Schizophreniaevenamidetreatment-resistant schizophreniaantipsychoticschizophreniaTRSadd-on treatment
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.