A Phase II, Randomized, 4-Week, Double-Blind, Placebo-Controlled, Multiple-Dose Study, Designed to Determine the Safety, Tolerability, EEG Effects and Preliminary Efficacy of Fixed Oral Doses of 7.5 and 15 MG BID of Evenamide in Patients With Chronic Schizophrenia Who Are Symptomatic on Their Current Second-Generation Antipsychotic Medication
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Schizophrenia
- Sponsor
- Newron Pharmaceuticals SPA
- Enrollment
- 138
- Locations
- 14
- Primary Endpoint
- Safety and tolerability - incidence of Treatment-Emergent Adverse Events [TEAEs], Serious Adverse Events [AEs], and Adverse Events leading to discontinuation [ADOs]
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This 4-week study will evaluate the safety, tolerability and preliminary evidence of efficacy of evenamide (7.5,and 15 mg and placebo, bid) treatment in outpatients with chronic schizophrenia.
Detailed Description
This is a prospective, 4-week, randomized, double-blind, placebo-controlled, study designed to evaluate the safety, tolerability, EEG effects, and preliminary efficacy of two fixed oral doses of evenamide of 7.5 mg and 15 mg bid (15 and 30 mg/day) in outpatients with chronic schizophrenia who are receiving treatment at constant doses of one of the following atypical antipsychotics: aripiprazole, clozapine, quetiapine, olanzapine, paliperidone or risperidone. Approximately 120 patients will be randomized in a 1:1:1 ratio to receive either evenamide 7.5 or 15 mg, or placebo, given bid.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Demographics
- •Age - 18 years, or older
- •Sex - male, or non-childbearing potential female unless practicing adequate contraception
- •Psychiatric
- •Has a current diagnosis of schizophrenia in accordance with DSM-
- •Has been treated with antipsychotics for at least 2 years.
- •Has a total score on the PANSS \<
- •Has a Clinical Global Impression - Severity of disease (CGI-S) rating of mildly, moderately or moderately severely ill (score of 3, 4 or 5).
- •Needs antipsychotic treatment and is currently receiving a stable dose (minimally for 4 weeks prior to screening) of aripiprazole, clozapine, quetiapine, olanzapine, paliperidone, or risperidone (at least 2 mg risperidone dose-equivalent)
- •Current symptoms have been stably present for at least one month
Exclusion Criteria
- •Psychiatric
- •Severity of current episode of psychosis requires that the patient be hospitalized. Patients who are chronically hospitalized or in psychiatric day-care, whose hospitalization is for logistic reasons and not due to the severity of their illness, will be eligible for the study.
- •Severity of psychosis is rated severe or higher (CGI-S of 6 or greater).
- •Known suicidal risk. A "yes" response on the C-SSRS Suicidal Ideation Item 4 or Item 5, or a "yes" response on any of the five C-SSRS Suicidal Behavior items, at screening, or a suicide attempt within the past 6 months, excludes the patient from the study.
- •Patients with a diagnosis of Treatment resistance
- •History of neuroleptic malignant syndrome, priapism.
- •Current moderate or severe tardive dyskinesia.
- •Medical Status
- •Abnormal epileptiform phenomena (3 per second spike and slow wave discharges) observed on screening EEG. History or current diagnosis of epilepsy or seizure disorder (other than febrile seizures in childhood)
- •Insulin-dependent diabetes mellitus
Arms & Interventions
Placebo
Matching placebo capsules BID for a total of 28 dosing days
Intervention: Placebo
Evenamide 15 mg bid
Evenamide capsules 15.0 mg BID for a total of 28 dosing days
Intervention: Evenamide
Evenamide 7.5 mg bid
Evenamide capsules 7.5 mg BID for a total of 28 dosing days
Intervention: Evenamide
Outcomes
Primary Outcomes
Safety and tolerability - incidence of Treatment-Emergent Adverse Events [TEAEs], Serious Adverse Events [AEs], and Adverse Events leading to discontinuation [ADOs]
Time Frame: 4 Week study
Comparison will be made between the evenamide and placebo groups in the proportion of patients experiencing Serious Adverse Events \[SAEs\], Adverse Events leading to discontinuation \[ADOs\] and, Treatment-Emergent Adverse Events \[TEAEs\].
Change from baseline in Positive and Negative Syndrome Scale [PANSS] total score
Time Frame: 4 Week study
Efficacy measure of mean change from baseline to endpoint of Positive and Negative Syndrome Scale \[PANSS\] total score: this is 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).
Secondary Outcomes
- Key secondary - Change from baseline in clinical global impression severity of Illness [CGI-S] score(4 Week study)
- Efficacy - rating score of patient satisfaction with the study medication(4 Week study)
- Comparison of plasma drug concentrations over time for evenamide and its major metabolite, (3-butoxy-phenyl)-acetic acid between the dosing arms 7.5 mg BID and 15.0 mg BID(4 Week study)
- Rating at endpoint on the CGI - Change from baseline (CGI-C)(4 Week study)
- Evaluate plasma drug concentrations over time for evenamide and its major metabolite, (3-butoxy-phenyl)-acetic acid(4 Week study)
- Efficacy - changes in daily functioning(4 Week study)