Home » Trials » SLCTR/2020/024


An open-label, multi-center, extension study to evaluate the long-term safety, tolerability and preliminary efficacy of evenamide as add-on treatment in patients with treatment-resistant schizophrenia (TRS) not responding adequately to their current antipsychotic medication

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SLCTR Registration Number

SLCTR/2020/024


Date of Registration

16 Nov 2020

The date of last modification

Nov 17, 2020



Application Summary


Scientific Title of Trial

An open-label, multi-center, extension study to evaluate the long-term safety, tolerability and preliminary efficacy of evenamide as add-on treatment in patients with treatment-resistant schizophrenia (TRS) not responding adequately to their current antipsychotic medication


Public Title of Trial

A long-term clinical study using Evenamide (orally taken new drug without masking its strength) to determine its safety, tolerability and efficacy in patients with treatment resistant schizophrenia, not befitting adequately from their current antipsychotic medication


Disease or Health Condition(s) Studied

Schizophrenia


Scientific Acronym

N/A


Public Acronym

N/A


Brief title

A long term clinical study to determine safety, tolerability and efficacy of drug called Evenamide which is taken orally, by patients with treatment resistant schizophrenia having inadequate benefit from their current antipsychotic medication


Universal Trial Number

U1111-1260-8404


Any other number(s) assigned to the trial and issuing authority

2020-000439-32 - EudraCT CTRI -CTRI/2020/09/027959


Trial Details


What is the research question being addressed?

What is the long-term safety, tolerability and preliminary efficacy of Evenamide as add-on treatment in patients with treatment-resistant schizophrenia (TRS) not responding adequately to their current antipsychotic medication


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Masking not used


Control

Dose comparison


Assignment

Parallel


Purpose

Treatment


Study Phase

Phase 2


Intervention(s) planned

•Study setting: Colombo North Teaching Hospital This is a 46-week, open-label, multi-center, extension to study NW-3509/014/II/2019 designed to evaluate the long-term safety, tolerability and preliminary efficacy of evenamide as add-on treatment in patients with treatment resistant schizophrenia on a stable therapeutic dose of an antipsychotic. In Study 014, 50 patients are to be randomized equally (1:1) to the 7.5 mg bid and 15 mg bid doses (approximately 25 in each group), and key safety data from these patients will be reviewed by an Independent Safety Monitoring Board (ISMB). If this review of the data indicates there are no safety issues, the 30 mg bid dose group will be initiated, and randomization will continue, with a total of approximately 50 patients being enrolled in each of the three treatment groups. If the 30 mg bid group is not added, the 150 patients will be randomly assigned (1:1) to the 7.5 and 15 mg bid treatment groups (approximately 75 in each group). Intervention NW3509 Fixed oral doses of 30 mg BID orally for 46 weeks therapy of NW-3509 (Evenamide)


Inclusion criteria

  1. Patient completed 6 weeks of treatment in Study NW-3509/014/II/2019
  2. Patient has provided written informed consent for this extension study.
  3. If female, patient is not of childbearing potential, pregnant or breastfeeding. For inclusion, female patients must be post-menopausal (age 50 or older with confirmed amenorrhea for >12 months), surgically sterilized, or protected with adequate contraception (barrier method or hormonal contraceptive).

Exclusion criteria

1) Protocol violation during 014 study. 2) Worsening of suicidal risk during 014 study 3) Moderate/severe neurological side effects during 014 study 4) Worsening of schizophrenia symptoms during study 014 5) Non compliance with dosing of study medication during 014



Primary outcome(s)

1.

Safety Evaluation: Safety will be assessed by the following: • Adverse events (AEs) • Vital signs systolic/diastolic blood pressure, pulse, body temperature, respiratory rate, body weight, BMI, waist circumference) • Laboratory evaluations - Haematology: Hematocrit, hemoglobin, RBC count, WBC count, differential WBC count, platelets

  • Blood Chemistry Sodium, Potassium, Chloride, Bicarbonate, Calcium, Glucose, BUN, Creatinine, total bilirubin, Albumin triglycerides, AST, ALT, alkaline phosphatase, GGT, LDH, total cholesterol, HDL, LDL, VLDL, CPK, total protein

  • Urinalysis pH, specific gravity, Protein, glucose, ketones, RBC, WBC, casts, Nitrites, bilirubin, hemoglobin

  • Serum prolactin

• ECG • Special Diagnostic Tests (evaluated at Screening and/or Baseline) Thyroid function: TSH, free triiodothyronine (T3), and free thyroxine (T4) (Screening) - Virology: Hepatitis B and C; HIV (Screening) - Urine drug screen (Screening, Baseline and final visit) - Alcohol breath test (Baseline) - Serum prolactin (Baseline and final visit) - Serum/urine pregnancy test (Screening, Baseline and final visit)

• Physical Examination

General appearance, skin, neck (including thyroid), eyes and ears, nose, mouth, throat, lungs, heart, abdomen, back, lymph nodes, extremities

• Neurological Examination: Evaluation of the mental status, cranial nerves, muscle strength and tone, reflexes, the sensory system, coordination and gait

• A standard eye examination Visual acuity (Snellen chart), visual field, eye muscles, pupillary response, fundus, tonometry, eyelids, cornea, conjunctiva, sclera and iris will be performed. The examination should be performed by a physician at the site who has the appropriate experience and training. If a clinically significant abnormality is noted that requires expert follow-up, an Ophthalmologist or Optometrist should be consulted.

• Seizure checklist

• Extrapyramidal Symptom Rating Scale - Abbreviated version (ESRS-A)

• Calgary Depression Scale for Schizophrenia (CDSS).

[

46 weeks

]

Secondary outcome(s)

1.

Preliminary Efficacy Evaluations

Preliminary Efficacy will be assessed by the following measures: • Positive and Negative Syndrome Scale (PANSS) total score - mean change from baseline to endpoint • Clinical Global Impression Severity of illness (CGI-S ) – mean change from baseline to endpoint

• Clinical Global Impression Change (CGI-C )– proportion of patients with improvement from baseline to endpoint (score of 1, 2 or 3), and mean score at endpoint

• PANSS – Positive Symptoms total score – mean change from baseline to endpoint

• PANSS – General Psychopathology total score – mean change from baseline to endpoint

• Level of Functioning (LOF) – mean change from baseline to endpoint

• PANSS – Negative Symptoms total score – mean change from baseline to endpoint.

[

46 weeks

]

Target number/sample size

Globally 100, Locally 21


Countries of recruitment

India, Italy, Malaysia, Sri Lanka


Anticipated start date

2021-03-01


Anticipated end date

2022-04-01


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Newron Pharmaceuticals S.p.A.


Regulatory approvals

Pending, Conditional approval received from NMRA



State of Ethics Review Approval


Status

Approved


Date of Approval

2020-08-06


Approval number

P/25/05/2020


Details of Ethics Review Committee

Name: University of Kelaniya
Institutional Address:Ethics- Review Committee, Faculty of Medicine, University of Kelaniya
Telephone:011-2961267
Email: ercmed@kln.ac.lk

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Prof Shehan Williams
Consultant Psychiatrist
Colombo North Teaching Hospital, Ragama

+94774301303

shehan@kln.ac.lk

Contact Person for Public Queries

Prof Shehan Williams
Consultant Psychiatrist
Colombo North Teaching Hospital, Ragama

+94774301303

shehan@kln.ac.lk


Primary study sponsor/organization

Dr Ravi Anand/Newron Pharmaceuticals S.p.A
Chief Medical Officer
Via Ludovico Ariosto 21, 20091 Bresso (Milano), Italy
+39-02-6103461

ravi@anand.ch

Secondary study sponsor (If any)







Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

No


IPD sharing plan description


Study protocol available

Yes


Protocol version and date

Protocol No. NW-3509/015/II/2019 Amendment 1, 13 February 2020


Protocol URL


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results