Treatment Resistant Schizophrenia
Conditions
Interventions
1. Study settings: • Colombo North Teaching Hospital • National Hospital Galle
2. Recruitment: Only patients who are determined to be suitable for enrolment in the trial by the Principal Investigato
Sponsors
Newron Pharmaceuticals S.p.A.
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age – 18 years, or older, at screening. The suitability of elderly patients (e.g., >80 years of age) for enrolment in the study should be discussed with the Medical Monitor. 2. If female, the subject has a negative pregnancy test at the screening visit and at baseline and is not lactating. 3. If female and of childbearing potential, the subject agrees to use adequate contraception, as determined by her Health Care Provider or according to local guidelines. Sexual abstinence is not an acceptable method of contraception. A woman is considered not to be of childbearing potential if she meets one of the following criteria: a. is post-menopausal (the last menstrual period was at least 12 months ago, and FSH at screening confirms post-menopausal status) b. has had a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Women who are taking hormone replacement therapy (HRT) must use adequate contraception (as described above) during the trial. 4. Body mass index (BMI) of at least 17.5 and less than 35. Patients with a BMI of less than 17.5, or 35 or higher, may be considered for enrolment on a case-by-case basis if, in the Investigator’s opinion, this does not put the patient at any additional risk for participating in the trial. These cases should be discussed with the Medical Monitor and documented in the source records. 5. Currently meets DSM-5-TR (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision) diagnostic criteria for schizophrenia, as confirmed by the Mini International Neuropsychiatric Interview (MINI) for Psychotic Disorders Studies 7.0.2. Other psychiatric disorders may be present as lifetime diagnoses if the current episode of schizophrenia is confirmed by the principal investigator (PI). [see Exclusion criteria below] 6. Confirmation of treatment resistance, according to the consensus guidelines from the Treatment Response and Resistance in Psychosis (TRRIP) working group, by documentation in the medical records that the patient has had no, or inadequate symptomatic relief in response to at least two antipsychotics, including one second-generation antipsychotic (SGA), despite treatment for at least 6 weeks at adequate doses as specified in the product label. 7. Requires antipsychotic treatment and is currently receiving “standard of care”, consisting of one or more oral (given for at least 6 weeks prior to screening) or depot (given for at least 2 cycles) antipsychotic(s) at a stable therapeutic dose(s), in accordance with the package insert (country specific). Only second-generation antipsychotics (Appendix 5, available on request) will be permitted as the primary antipsychotic. Other second-generation antipsychotics not on the list, as well as first-generation antipsychotics, will be allowed as secondary antipsychotics. The patient’s current antipsychotic(s) may be the same as one of the two antipsychotics the patient did not benefit from previously. If the minimum therapeutic dose of the primary antipsychotic is not tolerated, the maximum tolerated dose may be used. a. The plasma level of the concomitant primary antipsychotic measured at screening must be equivalent to or greater than the minimum plasma concentration that would correspond to a therapeutic dose of the drug (based on the manufacturer’s recommendation – a list of therapeutic plasma concentration ranges for the allowed second-generation antipsychotics will be provi
Exclusion criteria
Exclusion criteria: Psychiatric 1. Current DSM-5-TR diagnosis of schizophreniform disorder (295.40), schizoaffective disorder (295.70), or other primary psychiatric diagnosis, such as bipolar disorder or major depressive disorder (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-TR 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. Patients testing positive for THC on the urine drug screen will not be excluded from the study unless there is evidence of toxic psychosis. 3. Has been 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. Patients who are chronically hospitalized, or in psychiatric daycare, whose hospitalization is for logistic reasons and not due to the severity of their illness, will be eligible for the study. 4. Brief Psychiatric Rating Scale (BPRS) total score has improved by more than 20% from screening to baseline. 5. Clinical Global Impression–Severity (CGI-S) scale has improved by 1 point or more from screening to baseline. 6. Has a CGI-S rating of 7 (among the most extremely ill patients). 7. Has a history or current diagnosis of other psychiatric or behavioural disorders that may interfere with the conduct or interpretation of the study. 8. Has known suicidal risk. Patients who have exhibited suicidal behaviour 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. In making the assessment of suicidal risk, the Investigator should take into account the ratings on the Columbia-Suicide Severity Rating Scale (C-SSRS) (based on the past 1 month), with a ‘YES’ response on the Suicidal Ideation Item 4 or Item 5, or a ‘YES’ response on any of the five C-SSRS Suicidal Behaviour items being exclusionary. 9. Has a history of neuroleptic malignant syndrome or priapism. Medical 10. Has 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 significantly bias the assessment of the clinical or mental status of the patient or put the patient at special risk (e.g., liver or kidney disease, severe uncontrolled asthma, malignancy). 11. Has a disability that may prevent the subject from completing all study requirements (e.g., blindness, deafness, severe language difficulty). 12. Has 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. 13. Has a history or current diagnosis of any neurodegenerative illness, dementia, significant concomitant neurological disease, org
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Positive and Negative Syndrome Scale (PANSS) total change from baseline will be tested for the 15 mg and 30 mg bid dose groups versus placebo [Week 12 ] Safety and tolerability of fixed doses of evenamide of 15 mg bid and 30 mg bid : incidence of treatment-emergent adverse events (TEAEs), AEs leading to discontinuation (ADOs), and serious AEs (SAEs). [ Throughout the entire duration of the treatment ] | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in Clinical Global Impression–Severity (CGI-S) scale for the 15 mg and 30 mg bid dose groups versus placebo [Week 12] Change from baseline in Clinical Global Impression (CGI-C) scale for the 15 mg and 30 mg bid dose groups versus placebo [Week 12] Change in Positive Symptoms sub-scale score of the PANSS for the 15 mg and 30 mg bid dose groups versus placebo [Week 12] Change in PSP (Personal and Social Performance) scale will be tested for the 15 mg and 30 mg bid dose groups versus placebo [Week 12] Change in Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form) scale for the 15 mg and 30 mg bid dose groups versus placebo [Week 12] | — |
Countries
Argentina,Brazil,Bulgaria,Canada,Colombia,Croatia,Czech Republic,France,Germany,Hungary,India,Italy,Korea, Republic of,Malaysia,Mexico,Poland,Singapore,Spain,Sri Lanka,United Kingdom
Contacts
Public ContactProf. Shehan Williams
Principal Investigator
Outcome results
None listed