Treatment-resistant Schizophrenia
Conditions
Keywords
evenamide, treatment-resistant schizophrenia, antipsychotic, schizophrenia, TRS, add-on treatment
Brief summary
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.
Interventions
DRUGEvenamide 15 mg bid
Evenamide capsules 15 mg bid for a total of 12 weeks of add-on treatment
DRUGPlacebo
Matching placebo capsules bid for a total of 12 weeks of add-on treatment
Sponsors
Newron Pharmaceuticals SPA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to endpoint (Week 12) on the total score of the Positive and Negative Syndrome Scale (PANSS). | From Baseline to Week 12 | Efficacy measured by the mean change from baseline to endpoint of Positive and Negative Syndrome Scale \[PANSS\] total score: a 30-item scale that was designed to assess various symptoms of schizophrenia each rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). |
| Incidence of treatment-emergent adverse events (TEAEs), AEs leading to discontinuation (ADOs), and serious AEs (SAEs). | From Baseline to 30-day Safety Follow up (12 Weeks of treament + 30-day safety follow up) | Safety and tolerability of a dose of evenamide of 15 mg bid, compared to placebo. The assessment of safety and tolerability will be based primarily on the incidence of treatment-emergent adverse events (TEAEs), AEs leading to discontinuation (ADOs), and serious AEs (SAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to endpoint (Week 12) on the Clinical Global Impression - Severity of illness (CGI-S) score. | From Baseline to Week 12 | Efficacy measured by the mean change from baseline to endpoint on the Clinical Global Impression Severity of Illness (CGI-S) scale: a 7-point scale ranging from 1 (no symptoms) to 7 (very severe) to assess the severity of a subject's condition. |
| Proportion of patients rated as 'improved' on the CGI-C at endpoint (Week 12). | Week 12 | Efficacy measured by Clinical Global Impression of Change \[CGI-C\]: a 7-point scale, ranging from 1 (very much improved) to 7 (very much worse), with a score of 4 indicating "no change". Patients with ratings of 1,2 or 3 are considered as 'improved'. |
| Change from baseline to endpoint (Week 12) on the Positive Symptoms sub-scale score of the PANSS. | From Baseline to Week 12 | Efficacy measured by the mean change from baseline to endpoint on the Positive subscale score of the PANSS: a 7-item subscale designed to assess positive symptoms of schizophrenia each rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). |
| Change from baseline to endpoint (Week 12) on the Personal and Social Performance (PSP) scale. | From Baseline to Week 12 | Efficacy measured by the mean change from baseline to endpoint on the PSP scale: a 100-point single-item rating scale subdivided into 10 equal intervals that designed to assess the routine social functioning of patients with psychiatric disorders. |
| Change from baseline to endpoint (Week 12) on the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form scale (Q-LES-Q-SF). | From Baseline to Week 12 | Efficacy measured by the mean change from baseline to endpoint on the total score of the Quality of Life Enjoyment and Satisfaction Questionnaire: a 16-item scale, each rated from 1 (very poor) to 5 (very good). |
Countries
Argentina, India, Malaysia, United States
Contacts
CONTACTNewron Pharmaceuticals
STUDY_DIRECTORRavi Anand, MD
Newron Pharmaceuticals
Outcome results
None listed