CTRI/2021/04/032772已完成2 期
A Phase II, prospective, multi-center, randomized, 4-week, double-blind, placebo-controlled study, designed to determine the safety, tolerability, EEG effects and efficacy of oral doses of 30 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.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 15
- 主要终点
- 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.
研究概览
简要总结
17.8 Study Documentation and Publication of Study Results
Study Documentation
All unpublished documentation (including the protocol, Case Report Form and Investigator’s Brochure) given to the Investigator is strictly confidential. All recipients must agree not to disclose the information herein contained to any person not connected with the study without the prior written authorization of Newron Pharmaceuticals. The submission of these documents to the IRB/IEC is expressly permitted. The involved parties agree that the results of this study will be used in their original form and/or in a global report for submission to governmental and regulatory authorities of any country.
All information communicated to the investigator(s) by Newron is the exclusive property of Newron Pharmaceuticals S.p.A. The Principal Investigator will ensure this information shall be kept strictly confidential by him/her or any other person connected with the study and shall not be disclosed to any third party without the prior written consent of Newron.
Publication of Results
Any formal presentation or publication of the data from this trial will be considered as a joint publication by the Investigator(s) and Newron. Authorship will be determined by a Publication Committee consisting of the lead investigator(s) from the trial, representatives from Newron, and an external consultant with expertise in the field. For multi-center studies, it is mandatory that the first publication is based on data from all centers, analyzed as stipulated in the protocol by a statistician designated by Newron. Investigators participating in this study agree not to present or publish data gathered from a single center or sub-group of centers before the full initial publication, unless agreed to by all other investigators and Newron. Authorship of any publications resulting from pooled data will include members of each of the contributing centers, as well as Newron personnel.
Newron will form a study publication committee to coordinate and develop a publication policy and help in its implementation. The publication committee will be comprised of the Principal Investigator(s), a representative of Newron and an external consultant. Members of the publication committee cannot serve as first authors of more than one primary publication.
Any publication, abstract, or paper of any information or material relating to or arising out of the present clinical study shall be sent to Newron for review at least sixty (60) days before presentation at any congress, or publication of the final form(s) by any journal. Newron will inform the Investigator of any changes or deletions necessary to preserve Newron’s confidential and proprietary technical information. All rights and interests worldwide in any inventions, know-how or other intellectual or industrial property rights, which arise during the course and/or as a result of the present clinical study or which arise from the information or materials supplied under this Agreement, shall be assigned to, vest in and remain the property of Newron Pharmaceuticals S.p.A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Demographics
- •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.
- •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.
- •Body mass index (BMI) of at least 17.5 and less than
- •Psychiatric
- •Has a current diagnosis of schizophrenia in accordance with DSM-
- •Other Axis-I disorders may be present only as lifetime diagnoses if they are not relevant to the current episode of schizophrenia.
- •Has been treated with antipsychotics for at least 2 years.
- •Has a total score on the PANSS more than equal to 70 and less than equal to
- •Has a Clinical Global Impression – Severity of disease (CGI-S) rating of moderately, moderately severely, or severely ill (score of 4, 5 or 6).
- •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).
- •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
- •Patient has provided written informed consent prior to participating in the study.
- •Patient is able to take oral medication and is willing to complete all protocol-defined aspects of the study.
- •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.
- •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.
- •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.
排除标准
- •Psychiatric
- •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.)
- •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
- •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.
- •Severity of psychosis is rated very severe (CGI-S of 7).
- •History or current diagnosis of other psychiatric (Axis I diagnosis) or behavioral disorders that may interfere with the conduct or interpretation of the study.
- •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.
- •â€œTreatment 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.
- •Patient is currently in remission and/or experiencing transient mild breakthrough symptoms for which additional adjunctive treatment would not likely provide benefit.
- •History of neuroleptic malignant syndrome, priapism.
- •History of severe tardive dyskinesia; or current moderate or severe tardive dyskinesia.
- •Medical Status
- •Abnormal epileptiform phenomena (3 per second spike and slow wave discharges) observed on screening EEG.
- •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).
- •A disability that may prevent the subject from completing all study requirements (e.g., blindness, deafness, severe language difficulty).
- •Insulin-dependent diabetes mellitus.
- •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.
- •History or current diagnosis of any neurodegenerative illness, dementia or 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).
- •Loss of 500 ml or more of blood during the 3-month period before study enrollment, e.g. as a donor.
- •Prior surgery or current medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug, e.g. gastric or intestinal surgery, impaired renal or hepatic function, cardiovascular abnormalities, inflammatory bowel disease, chronic symptoms of pronounced constipation or diarrhea, or conditions associated with total or partial obstruction of the urinary tract.
- •Cardiovascular
- •A current diagnosis of severe or unstable cardiovascular disease, including ischemic heart disease; vasovagal syncope, sick-sinus syndrome, arrhythmia, conduction deficits [e.g., sino-atrial block, second or third degree atrio-ventricular block (PR >0.20)], congestive heart failure, myocardial infarction, coronary artery bypass surgery, or percutaneous transluminal coronary angioplasty.
- •Any clinically significant ECG abnormality, including a disorder of rate, rhythm, or conduction, or other morphological changes, or a QTcF interval prolongation (Fridericia’s correction formula) on the ECG (>450 msec for males; >470 msec for females).
- •Vital signs (supine) outside the following ranges (measured after 5 minutes supine): a.
- •Systolic blood pressure below 100 or above 150 mmHg; b.
- •Radial pulse (from vital signs) below 50 or above 100 bpm; d.
- •Orthostatic hypotension (decrease in SBP/DBP from supine to standing position exceeding 30 mmHg);
- •History of myocardial infarction, coronary artery bypass surgery, or percutaneous transluminal coronary angioplasty.
- •Laboratory abnormalities
- •Clinically significant abnormalities in routine laboratory examinations (hematology; blood chemistry, including electrolytes and liver and kidney function tests; urinalysis), as determined by the Principal Investigator in consultation with the Medical Monitor, at the screening evaluation.
- •Tables of clinically notable values for laboratory parameters in Appendix 2 should be used as a guide in making this determination.
- •History of hepatitis B and/or C, and/or positive serology results, which indicate the presence of hepatitis B and/or C (Hepatitis B surface antigen and/or antibody to Hepatitis C); as identified by any of the following: a.
- •Hepatitis B: hepatitis B surface antigen (HBsAg) or with isolated anti-HBc (HBsAg negative, anti-HBc positive, and anti-HBs negative); b.
- •Hepatitis C: antibody to hepatitis C positive and HCV RNA positive.
- •Positive results from the HIV serology.
- •Positive results of the drug and alcohol tests at screening and/or baseline.
- •Patients who test positive for drugs of abuse at screening, but have negative test results at baseline, may be eligible, depending on the type of drug and the likelihood of continued abuse during the study.
- •Clinically significant hypothyroidism or hyperthyroidism, unless stabilized by medication for at least 3 months before screening.
- •Concomitant therapy
- •Patients treated with anticholinergic drugs whose dose is not stable at baseline.
- •The lowest dose possible should be used.
- •Occasional prn use is permitted.
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结局指标
主要结局
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.
时间窗: 28 Days
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.
时间窗: 28 Days
次要结局
- 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).(28 days)
研究者
研究点 (15)
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