A clinical study to determine safety, tolerability and efficacy of drug called Evenamide which is taken orally, in patients with long standing schizophrenia getting inadequate benefit from their current antipsychotic medication.
- Conditions
- Health Condition 1: F20-F29- Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders
- Registration Number
- CTRI/2021/04/032772
- Lead Sponsor
- ewron Pharmaceuticals SpA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 112
Demographics
2. Female subjects must have a negative pregnancy test at the screening visit and at baseline and must not be lactating.
- If of childbearing potential, the subject must use a highly effective method of contraception (i.e., a method that can achieve a failure rate of less than 1percent per year when used consistently and correctly) during the trial, from at least 28 days before the first dose until the final follow-up visit. Highly effective methods of contraception include-
- A woman is considered to be of non-childbearing potential if she meets one of the following criteria:
-is post-menopausal (the last menstrual period was at least 12 months ago, and FSH at screening confirms post-menopausal status),
-has no uterus, ovaries or fallopian tubes.
- Women who are taking hormone replacement therapy (HRT) must use contraception (as described above) during the trial.
- Sexual abstinence is not an acceptable method of contraception.
3. Male subjects who are not sterilized must agree to not have sex without using a condom, if their partner is a woman of childbearing potential, during the trial (from the first dose until the final follow-up visit). Male subjects must also agree not to attempt to father a child and must not donate sperm from the first dose until the final follow-up visit.
4. Body mass index (BMI) of at least 17.5 and less than 35.
Psychiatric
5. Has a current diagnosis of schizophrenia in accordance with DSM-5. Other Axis-I disorders may be present only as lifetime diagnoses if they are not relevant to the current episode of schizophrenia.
6. Has been treated with antipsychotics for at least 2 years.
7. Has a total score on the PANSS more than equal to 70 and less than equal to 85.
8. Has a Clinical Global Impression – Severity of disease (CGI-S) rating of moderately, moderately severely, or severely ill (score of 4, 5 or 6).
9. 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).
10. Current symptoms have been stably present for at least one month.
Patients must be symptomatic enough to benefit from addition of another antipsychotic while on their current antipsychotic; in general, these patients will have PANSS scores between 70 and 85 and a CGI-S of 4, 5 or 6.
Procedural
11. Patient has provided written informed consent prior to participating in the study.
12. Patient is able to take oral medication and is willing to complete all protocol-defined aspects of the study.
13. Patient resides at home or in a residential care facility with a caregiver who is available to ensure compliance with dosing and scheduled office visits. For US only: Caregiver is defined as someone who has at least 5 contacts with the patient each week, of which at least 2 are face-to-face.
14. Patient agrees to be hospitalized overnight if required for trial purposes or if the investigator deems it necessary to ensure the safety of the patient.
15. If taking clozapine, patient agrees to blood monitoring (venipuncture for measuring ANC) weekly during their first 6 months of clozapine treatment, every 2 weeks from 6 to 12 months, and every 4 weeks after 12 months of treatment. <
Psychiatric
1. DSM-5 diagnosis of schizophreniform disorder (295.40), schizoaffective disorder (295.70), or other primary psychiatric diagnosis, such as bipolar disorder or major depressive disorder. (Comorbid depression will be assessed at screening and baseline using the Calgary Depression Scale for Schizophrenia [CDSS]. A score of 7 or higher will be exclusionary.)
2. History (within three months of study entry) or current diagnosis of Substance Use Disorder as defined by the DSM-5 criteria, with a severity of ‘moderate’ or ‘severe’, or patient is currently abusing drugs or alcohol or has done so in the past year. A history of nicotine or caffeine dependence is acceptable
3. 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.
4. Severity of psychosis is rated very severe (CGI-S of 7).
5. History or current diagnosis of other psychiatric (Axis I diagnosis) or behavioral disorders that may interfere with the conduct or interpretation of the study.
6. Known suicidal risk. Patients who have exhibited suicidal behavior within the past 6 months, as indicated by an actual attempt, interrupted attempt, aborted attempt, or preparatory acts will be excluded from participating in the trial.
7. Treatment resistant ? defined significant persistent symptoms of schizophrenia after adequate doses of two standard antipsychotic medications (from two different chemical classes, including at least one atypical antipsychotic) following 6 weeks of treatment with each at adequate doses. Treatment resistant patients on clozapine for at least 6 months will be permitted if they have shown minimal improvement in the Investigator’s judgement.
8. Patient is currently in remission and/or experiencing transient mild breakthrough symptoms for which additional adjunctive treatment would not likely provide benefit.
9. History of neuroleptic malignant syndrome, priapism.
10. History of severe tardive dyskinesia; or current moderate or severe tardive dyskinesia.
Medical Status
11. Abnormal epileptiform phenomena (3 per second spike and slow wave discharges) observed on screening EEG.
12. An advanced, severe, or unstable disease of any type that may interfere with any of the study evaluations, including any medical condition that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical or mental status of the patient to a significant degree or put the patient at special risk (e.g., respiratory, liver or kidney disease; malignancy).
13. A disability that may prevent the subject from completing all study requirements (e.g., blindness, deafness, severe language difficulty).
14. Insulin-dependent diabetes mellitus. Patients with non-insulin-dependent diabetes will be eligible if the following criteria are satisfied:
a. HbA1c < 7.0% at screening,
b. Diabetes is considered well controlled, with no changes in treatment regimen for at least 4 weeks prior to screening,
c. Diabetes is not newly diagnosed at screening.
15. History or current diagnosis of any neurodegenerative illness, dementia or significant concomitant neurological dise
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety: To evaluate safety and tolerability of evenamide (30mg bid), achieved with 15 mg bid, compared to placebo, in patients with schizophrenia who are being treated with stable doses aripiprazole, clozapine, quetiapine, olanzapine, paliperidone or risperidone. <br/ ><br>Efficacy: To evaluate efficacy of evenamide at 30 mg bid, achieved with 15 mg bid, compared to placebo, based on improvements in symptoms of schizophrenia, as assessed by the PANSS total score.Timepoint: 28 Days
- Secondary Outcome Measures
Name Time Method To evaluate the efficacy of 30mg bid of evenamide, achieved after a 1-week titration starting with 15 mg bid, compared to placebo, based on improvements in symptoms of schizophrenia, as assessed by the Clinical Global Impression - Severity of illness (CGI-S).Timepoint: 28 days