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.
Scientific Title of Study
A Phase II, prospective, multi-center, 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 (NW-3509) in patients with chronic schizophrenia who are symptomatic on their current second-generation antipsychotic (aripiprazole, clozapine, quetiapine, olanzapine, paliperidone, or risperidone) medication.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
104.708
Other
NW-3509/008/II/2019 Amendment 2, 23 December 2019
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Shiv Issar
Designation
Head, Clinical and RA
Affiliation
CliniRx Research Pvt Ltd
Address
Patriot House, 4th Floor
3 BSZ Marg, New Delhi Patriot House, 4th Floor
3 BSZ Marg, New Delhi Central DELHI 110002 India
Phone
9868167119
Fax
Email
shiv.issar@clinirx.com
Details of Contact Person Scientific Query
Name
Shiv Issar
Designation
Head, Clinical and RA
Affiliation
CliniRx Research Pvt Ltd
Address
Patriot House, 4th Floor
3 BSZ Marg, New Delhi Patriot House, 4th Floor
3 BSZ Marg, New Delhi Central DELHI 110002 India
Phone
9868167119
Fax
Email
shiv.issar@clinirx.com
Details of Contact Person Public Query
Name
Shiv Issar
Designation
Head, Clinical and RA
Affiliation
CliniRx Research Pvt Ltd
Address
Patriot House, 4th Floor
3 BSZ Marg, New Delhi Patriot House, 4th Floor
3 BSZ Marg, New Delhi Central DELHI 110002 India
Phone
9868167119
Fax
Email
shiv.issar@clinirx.com
Source of Monetary or Material Support
Newron Pharmaceuticals SpA
Via Ludovico Ariosto 21
20091 Bresso (Milano)
Italy
Primary Sponsor
Name
Newron Pharmaceuticals SpA
Address
Via Ludovico Ariosto 21
20091 Bresso (Milano)
Italy
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
CliniRx Research Pvt Ltd
Patriot House, 4th Floor, 3 BSZ Marg, New Delhi-110002
Department of Psychiatry, No. 11, Subburam Street, Gandhi Nagar, Madurai-625020 Madurai TAMIL NADU
9443772233
vikhram@ahanahospitals.in
Dr Gundugurti Prasad Rao
Asha Hospital
Department of Psychiatry, Road No.14, Banjara Hills, Hyderabad-500034 Hyderabad TELANGANA
9985900005
Prasad40@gmail.com
Dr Ranjive Mahajan
Dayanand Medical College & Hospital
Department of Psychiatry, Research & Development Centre,
Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines - 141001 Ludhiana PUNJAB
9872655006
ranjive@yahoo.com
Dr Sanjay Phadke
Deenanath Mangeshkar Hospital Research Center
Department of Psychiatry,
Near Mhatre Briddge, Erandwane, -411004 Pune MAHARASHTRA
9823262786
sanjay_phadke@hotmail.com
Dr Radhika Reddy
Help Hospitals Private Limited
Department of Psychiatry, Help Hospitals Private Limited., D. No: 27-29-23, Behind Victoria Museum, Governorpet, Vijayawada, Andhra Pradesh, India. Pincode-520002 Vizianagaram ANDHRA PRADESH
9848229798
rrvemireddy@yahoo.com
Dr PN Suresh Kumar
IQRAA Psychiatric Care and Rehabilitation Centre
Department of Psychiatry, IQRAA International Hospital and Research center, Near Vyapar Bhavan, Civil Station (PO), Eranhipalam-673020 Kozhikode KERALA
9447218825
drpnsuresh@gmail.com
Dr Supriya Hegde
Mangala Hospital and Mangala Kidney Foundation
Department of Psychiatry, Mangala Hospital and Mangala Kidney Foundation, Vajra Hills, Kadri Road -575003 Mangalore Mysore KARNATAKA
9845338287
aroor.supriya@gmail.com
Dr Vijay Kumar KG
National Institute of Mental Health and Neurosciences
Department of Psychiatry, Hosur Road, Wilson Garden,Bengaluru-560029, India Bangalore KARNATAKA
9985900005
vkkg24@gmail.com
Dr Sandeep Grover
Post Graduate Institute of Medical Education and Research
Department of Psychiatry, Nehru Hospital, Department of Psychiatry, Cobalt Block, PGIMER, 160012-Chandigarh Patiala PUNJAB
9316138997
drsandeepg2002@yahoo.com
Dr Sanjeev Saoji
Saoji Tupkari Hospital
Department of Psychiatry
4, Vijay Nagar, Garkheda Road, -431005 Aurangabad MAHARASHTRA
9822957746
sanjeev.saoji@gmail.com
Dr Ramanathan Sathianathan
Sri Ramachandra Hospital
Department of Psychiatry, Sri Ramachandra University,
No:1 Ramachandra Nagar, Porur – 600116 Chennai TAMIL NADU
9841019910
sathianathen6@yahoo.com
Dr Johnson Pradeep
St Johns Medical College hospital, Department of Psychiatry
Department of Psychiatry, St Johns Medical College & Hospital, St Johns National Academy of health Science, Sarjapur Main Road, 560034 Bangalore KARNATAKA
9632175933
drjohnsonpradeep@gmail.com
Dr Umesh Nagapurkar
Sujata Birla Hospital and Medical Research Centre
Department of Psychiatry, Opposite Bytco College, Nashik Road Nashik MAHARASHTRA
Drug Trial Ethics Committee, Dayanand Medical College and Hospital
Approved
Ethics Committee - Help Hospitals Private Limited, D. No: 27-29-23, Behind Victoria Museum, Governorpet, Vijayawada, Andhra Pradesh, India. ECR/1356/Inst/TN/2020
Approved
Ethics committee Asha Hospital,
Approved
Ethics committee, Radianz Healthcare and Research
Approved
Institute Ethics Committee, PGIMER
Approved
Institutional Ethics Committee, Deenanath Mangeshkar Hospital and Research Centre
Approved
Institutional ethics committee, IQRAA International Hospital and Research center
Approved
Institutional Ethics Committee, Sri Ramachandra Medical College and Research Institute
Approved
Institutional Ethics Committee, St. John’s Medical College Hospital,
Approved
Mangala Institutional Ethics Committee, Mangala Hospital and Mangala Kidney Foundation
Approved
NIMHANS Ethics Committee, Administrative Block, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, Karnataka-560029, India
Submittted/Under Review
Saoji Tupkari Hospital Ethics Committee
Approved
Yash Society’s Sujata Birla Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: F208||Other schizophrenia,
Intervention / Comparator Agent
Type
Name
Details
Intervention
NW3509
Fixed oral doses of 7.5 and 15 mg BID orally for 28 days therapy of NW-3509 (Evenamide)
Comparator Agent
Placebo
Placebo BID orally for 28 days therapy of NW-3509 (Evenamide)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Psychiatric
4. 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. [see Exclusion criteria below]
5. Has been treated with antipsychotics for at least 2 years.
6. Has a total score on the PANSS < 80.
7. Has a Clinical Global Impression – Severity of disease (CGI-S) rating of mildly, moderately or moderately severely ill (score of 3, 4 or 5).
8. 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).
9. Current symptoms have been stably present for at least one month.
Procedural
10. Patient has provided written informed consent prior to participating in the study.
11. Patient is able to take oral medication and is willing to complete all protocol-defined aspects of the study.
12. 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.
13. 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.
14. 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.
ExclusionCriteria
Details
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 severe or higher (CGI-S of 6 or greater).
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. 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.
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. History of neuroleptic malignant syndrome, priapism.
9. History of severe tardive dyskinesia; or current moderate or severe tardive dyskinesia.
Medical Status
10. Abnormal epileptiform phenomena (3 per second spike and slow wave discharges) observed on screening EEG.
11. 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);
12. A disability that may prevent the subject from completing all study requirements (e.g., blindness, deafness, severe language difficulty);
13. Insulin-dependent diabetes mellitus. Patients with non-insulin-dependent diabetes will be eligible if the following criteria are satisfied:
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
To evaluate the safety and tolerability (including EEG and ECG effects) of two fixed oral doses of evenamide (7.5 and 15 mg bid [15 and 30 mg/day]), compared to placebo, in patients with schizophrenia who are being treated with stable doses of antipsychotic medication (aripiprazole, clozapine, quetiapine, olanzapine, paliperidone or risperidone).
28 Days
Secondary Outcome
Outcome
TimePoints
To evaluate evidence for efficacy of evenamide in a range from 7.5 to 15 mg bid, compared to placebo, based on improvements in symptoms of schizophrenia, as assessed by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression - Change from baseline (CGI-C) and Severity of illness (CGI-S)
4 Weeks
Target Sample Size
Total Sample Size="120" Sample Size from India="100" Final Enrollment numbers achieved (Total)= "138" Final Enrollment numbers achieved (India)="111"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a prospective, 4-week, randomized, double-blind, placebo-controlled, study designed to evaluate the safety, tolerability, including effects on EEG recordings, and preliminary efficacy of two fixed oral doses of evenamide of 7.5 mg and 15 mg bid (15 and 30 mg/day) in patients 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. Immediately following completion of the 4-week double-blind phase, participants may enter a 48-week open-label extension study (Study NW-3509/009/II/2019) in which all patients will receive treatment with evenamide.