Clinical trial NCT04461119: Study to Determine the Safety, Tolerability, and Efficacy of Evenamide in Patients With Chronic Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: Newron Pharmaceuticals SPA
Sponsor class: INDUSTRY
First posted: 2020-07-08
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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-5.
* Has been treated with antipsychotics for at least 2 years.
* Has a total score on the PANSS \< 80.
* 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

Procedural

* Patient resides at home or in a residential care facility
* If taking clozapine, patient agrees to blood monitoring

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
* History or current diagnosis of any neurodegenerative illnesses
* Loss of 500 ml or more of blood during the 3-month period before study enrollment, e.g. as a donor

Cardiovascular

* A current diagnosis of severe or unstable cardiovascular disease
* Any clinically significant ECG abnormality
* Abnormal vital signs

Laboratory abnormalities

* Clinically significant abnormalities in routine laboratory examinations
* History and/or presence of hepatitis B and/or C
* Positive results from the HIV serology.
* Positive results of the drug and alcohol tests
* Clinically significant or unstable hypothyroidism or hyperthyroidism

Concomitant therapy

* Treatment with SSRIs that are moderate/potent inhibitors of CYP2D6 (e.g. fluoxetine)
* Treatment with drugs capable of inducing/inhibiting hepatic enzyme metabolism
* Current treatment with sodium channel blockers
* Exposure to any investigational drug within 5 weeks or 5 half-lives (whichever is longer) prior to screening
* A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to evenamide (e.g. lamotrigine, carbamazepine, oxcarbazepine, topiramate, etc.), or any components of the evenamide or matching placebo capsules
* Treatment with a drug or treatment known to cause major organ system toxicity, e.g. tamoxifen, within 4 weeks, or received radiation therapy or a drug with cytotoxic potential, e.g. chemotherapy, during the past year
* Electroconvulsive therapy (ECT) or treatment with a transcranial magnetic stimulation (TMS) device within 6 months prior to screening

Primary outcomes:
measure: Safety and tolerability - incidence of Treatment-Emergent Adverse Events [TEAEs], Serious Adverse Events [AEs], and Adverse Events leading to discontinuation [ADOs]
timeFrame: 4 Week study
measure: Change from baseline in Positive and Negative Syndrome Scale [PANSS] total score
timeFrame: 4 Week study
Secondary outcomes:
measure: Key secondary - Change from baseline in clinical global impression severity of Illness [CGI-S] score
timeFrame: 4 Week study
measure: Rating at endpoint on the CGI - Change from baseline (CGI-C)
timeFrame: 4 Week study
measure: Evaluate plasma drug concentrations over time for evenamide and its major metabolite, (3-butoxy-phenyl)-acetic acid
timeFrame: 4 Week study
measure: 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
timeFrame: 4 Week study
measure: Efficacy - changes in daily functioning
timeFrame: 4 Week study
measure: Efficacy - rating score of patient satisfaction with the study medication
timeFrame: 4 Week study
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Behavioral Research Specialists, LLC
state: California
city: Gaithersburg
country: United States
facility: CBH Health, LLC
state: Maryland
city: Austin
country: United States
facility: Community Clinical Research CCR
state: Texas
city: Vijayawada
country: India
facility: Help Hospitals Clinical Research Department
state: Andhra Pradesh
city: Koramangala
country: India
facility: St. John's Medical College Hospital
state: Karnataka
city: Mangalore
country: India
facility: Mangala Hospital and Mangala Kidney Foundation, Department of Psychiatry
state: Karnataka
city: Kozhikode
country: India
facility: IQRAA Psychiatry Care and Rehabilitation Centre
state: Kerala
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital Research Center
state: Maharashtra
city: Pune
country: India
facility: Sujata Birla Hospital
state: Maharashtra
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research
state: Punjab
city: Ludhiana
country: India
facility: Dayanand Medical College & Hospital
state: Punjab
city: Chennai
country: India
facility: Sri Ramachandra Medical College, Department of Psychiatry
state: Tamil Nadu
city: Madurai
country: India
facility: Ahana Hospital LLP
state: TamilNadu
city: Hyderabad
country: India
facility: Asha Hospital
state: Telangana
Study officials:
affiliation: Newron Pharmaceuticals
name: Ravi Anand, MD
role: STUDY_DIRECTOR
References: