A pilot, open-label, rater-blinded, randomized, parallel-group, multi-center study to evaluate the safety, tolerability and preliminary efficacy of three add-on fixed doses of Evenamide in patients with treatment-resistant schizophrenia (TRS).
- Conditions
- Schizophrenia not responding adequately to current antipsychotic treatmentMedDRA version: 20.0Level: LLTClassification code 10072913Term: Treatment-resistant schizophreniaSystem Organ Class: 100000004873Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2020-000437-41-IT
- Lead Sponsor
- EWRON PHARMACEUTICALS SPA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 150
1. Age - 18 years, or older.
2. Sex – male, or female not of childbearing potential, unless using adequate
contraception, as determined by their Health Care Provider.
3. Meets current DSM-5 criteria for schizophrenia. Other psychiatric disorders may be
present only as lifetime diagnoses if they are not relevant to the current episode of
schizophrenia. [see Exclusion criteria below]
4. Has been diagnosed with schizophrenia within the past 10 years.
5. Has shown treatment-resistance according to psychiatric history, with the last failed
treatment documented in the patient’s clinical records. Treatment-resistant
Schizophrenia” (TRS) is defined as a persistence of significant clinical symptoms
despite adequate doses of two standard antipsychotic medications (other than clozapine)
from two different chemical classes, including at least one atypical antipsychotic, for
at least 6 weeks of treatment each. The last failed treatment trial must be documented.
6. Has a Clinical Global Impression – Severity of disease (CGI-S) rating of moderately
ill to severely ill (score of 4 to 6 [scale 1-7]).
7. Has a PANSS total score = 70 at screening and baseline.
8. Has a score of 4 (moderate) or more on at least 2 of the following 4 PANSS symptoms
of psychosis: P2 (Conceptual Disorganization), P3 (Hallucinatory Behavior), P6
(Suspiciousness/Persecution) and G9 (Unusual Thought Content); and a total score of at
least 20 on the combined total of the PANSS symptom items: P1 (Delusions), P2
(Conceptual Disorganization), P3 (Hallucinatory Behavior), P4 (Excitement), P6
(Suspiciousness/Persecution), P7 (Hostility), and G9 (Unusual thought content).
9. Has a Global Assessment of Functioning (GAF) scale total score = 50.
10. Is in need of anti-psychotic treatment and is currently receiving mono-therapy at a
stable dose (minimally for 4 weeks prior to screening) at a minimal recommended
therapeutic or higher dose of one antipsychotic (atypical or typical, other than
clozapine). Current use of quetiapine at a dose of 150 mg or less at night as a
soporific will not be considered polypharmacy.
11. Current level of symptoms has been present for at least one month, but not exceeding
one year.
12. Patient is cooperative, able to take oral medication, able to understand the
instructions and willing to complete all aspects of the study, and is capable of doing
so.
13. Patient is residing with a caregiver at his/her home, or is either in a residential
care facility or residing alone, with a caregiver available to help ensure compliance
with dosing and scheduled office visits in either situation.
14. Patient has provided written informed consent prior to participating in the study.
15. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 143
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7
1. DSM-5 diagnosis of schizophreniform disorder, schizoaffective disorder, or other primary psychiatric diagnosis
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
3. Severity of current episode of psychosis requires that the patient be hospitalized
4. Has a PANSS total score > 90 or a CGI-S rating of 7
5. History or current diagnosis of other psychiatric or behavioral disorders
6. Known suicidal risk, or a suicide attempt within the past 2 years
7. History of neuroleptic malignant syndrome, priapism or moderate or severe tardive dyskinesia
8. An advanced, severe, or unstable disease of any type that may interfere with any of the study evaluations
9. Insulin-dependent diabetes mellitus
10. History or current diagnosis of any neurodegenerative illness, dementia, significant concomitant neurological disease, organic cerebral disease, cerebrovascular disease, focal neurological lesions or history of any trauma resulting in loss of consciousness (during the past 2 years)
11. History or current diagnosis of epilepsy or seizure disorder, or occurrence of a seizure within the past year, or repeated drug-induced seizures
12. Prior surgery or current medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug
13. Any clinically significant ECG abnormality, including a disorder of rate, rhythm, or conduction, or other morphological changes, or a QTcF interval prolongation
14. Vital signs outside the following ranges:
a.Systolic blood pressure < 90 or > 150 mmHg;
b.Diastolic blood pressure < 50 or > 95 mmHg;
c.Radial pulse (from vital signs) < 50 or > 100 bpm;
d.Orthostatic hypotension
15. History of hepatitis B and/or C, and/or positive serology results, which indicate the presence of hepatitis B and/or C
16. Positive results from the HIV serology
17. Positive results of the drug and alcohol tests at screening and/or baseline
18. History of or current treatment with clozapine for psychosis
19. Requires treatment with an anticholinergic drug, and the dose is not stable
20. Receiving benzodiazepine therapy, unless the dose has been stabilized for at least 2 months
21. Treatment with agents influencing dopamine, norepinephrine or serotonin neurotransmission
22. Treatment with drugs capable of inducing/inhibiting hepatic enzyme metabolism (e.g. barbiturates, carbamazepine, phenylbutazone, phenytoin, primidone, rifampicin) four weeks prior to baseline or during the study
23. Current treatment with sodium channel blockers or mood stabilizers; Valproic acid will be permitted, if used as maintenance treatment
24. Exposure to any investigational drug within 5 weeks or 5 half-lives prior to screening
25. A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to evenamide, or any components of the evenamide capsules
26. Electroconvulsive therapy (ECT) or treatment with a transcranial magnetic stimulation (TMS) device within 6 months prior to screening
27. Patient is female and of childbearing potential, pregnant or breastfeeding. For inclusion, female patients must be post-menopausal, surgically sterilized, or using adequate contraception
28. Patients with a reasonable likelihood of non-compliance with the protocol, or any other reason that, in the Investigat
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method