CTRI/2017/06/008857进行中（未招募）不适用
A randomized, multi center,openlabel,two-treatment, wo-period, two-sequence,multiple dose,crossover,steadystatebioequivalence study of Clozapinetablets25 mg ofChangzhou Pharmaceutical Factory,Chinavs.Clozaril@ 25mg Tablets, Distributed by:NovartisPharmaCorporation EastHanover,NJ 07936in adultschizophrenic patientsalreadyreceivingstable dailydoseof Clozapine 25mgtabletwicedailyunderfasting condition
适应症
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- To demonstrate the bioequivalence at steady state of Clozapine tablets 25 mg of Changzhou Pharmaceutical Factory, China vs. Clozaril® 25 mg Tablets, distributed by: Novartis Pharma Corporation East Hanover, NJ 07936 in adult schizophrenic patients already receiving stable daily dose of Clozapine 25 mg tablet twice daily under fasting conditions.
研究概览
简要总结
The therapeutic efficasy of clozapine in Schizophrenia is modified through antagonism of the dopamine type 2 (D2) and the serotonin type 2A (5-HT2A) receptors. Clozapine also acts as an antagonist at adreneric,cholinergic,histaminergi and other dopaminergic and serotonergic receptors. The study will carried out on adult Schizophrenic patients already receiving stable daily dose of clozapine 25 mg tablet twice daily under fasting conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Men and women aged 18-65 years (both inclusive) having clinical diagnosis of schizophrenia (DSM IV-TR).
- •2.Patients have a diagnosis of treatment-resistant schizophrenia {Treatment resistance is defined as an inadequate response to at least two antipsychotic drugs at the maximally tolerated dose within the recommended therapeutic range in treatment lasting six weeks or more.
- •Termination of a medication due to adverse events before reaching the appropriate dose and duration should not be regarded as a failed treatment due to non response to the medication.
- •3.Schizophrenic patients who are on stable dose of Clozapine 25 mg for at least 3 months prior to randomization and receiving Clozapine 25 mg twice daily.
- •4.Patients should be otherwise healthy as determined by physical examination, medical history, and routine hematologic and biochemical tests.
- •6.Females of childbearing potential (sexually active women who have not completed 1 year after menopause & have not gone through hysterectomy or bilateral tubal ligation) must have a negative pregnancy test (at screening and prior to check-in in Period I) as well as must be non-lactating at screening and must agree to use an effective contraceptive method during study.
- •7.No participation in any clinical study within the past 90 days.
排除标准
- •1.A history of allergic reactions to Clozapine / any of the component of study drug or other chemically related psychotropic drugs 2.Concurrent primary psychiatric disorder other than schizophrenia or neurological diagnosis, including organic mental disorder, neuroleptic malignant syndrome, severe tardive dyskinesia, or idiopathic Parkinson’s disease and dementia related psychosis, a history of epilepsy or other predisposing risk factors for seizures, history of multiple syncopal attacks or any other clinically significant CNS disorder.
- •3.Patients with the following cardiac conditions: •Recent myocardial infarction (<12 months) •QTc prolongation (screening electrocardiogram with QTc >450 msec for men, QTc >470 msec for women) •History of QTc prolongation or using concomitant medications which prolong QTc interval.
- •â€¢Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia •Uncompensated congestive heart failure, myocarditis, cardiomyopathy •Complete left bundle branch block •First-degree heart block with PR interval > 0.22 seconds 4.Patients with significant renal or hepatic impairment in which dose reduction is necessary as per the clinical evaluation of the patient by the Investigator.
- •5.Patients with narrow-angle glaucoma, concomitant anticholinergic medications, prostatic hypertrophy, or other conditions in which anticholinergic medications are required for the treatment, paralytic ileus, intestinal obstruction etc.
- •6.Patients with known history of CYP2D6 poor metabolizers.
- •7.A history of granulocytopenia/ agranulocytosis or myeloproliferative disorders (drug-induced or idiopathic) 8.Patient with the history or presence of orthostatic hypotension (i.e., a drop in systolic blood pressure of 30 mm Hg or more and/or a drop in diastolic blood pressure of 20 mm Hg or more on standing) at the time of screening.
- •9.Concurrent use of antihypertensive medication or any medication that might pre¬dispose to orthostatic hypotension 10.A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of Clozapine 11.Any of the following hematological abnormality at screening •Total white blood cell count < 4000/c.mm •Absolute neutrophil count < 2000/c.mm •Absolute eosinophil count > 700 / c.mm •Patients with poor glycemic control as defined by HbA1c ≥7% and/or fasting blood glucose >160 mg/dL at screening •Patients with total cholesterol >300 mg/dL and triglycerides level > 300 mg/dL at screening 12.Concurrent use of other drugs known to suppress bone marrow function 13.Expected changes in concomitant medications during the period of study.
- •14.Positive tests for drug or alcohol abuse at screening or baseline.
- •15.A history of alcohol or drug dependence by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria during the 6-month period immediately prior to study entry.
- •16.History of multiple syncopal episodes.
- •17.Patients have a history of narrow-angle glaucoma 18.Use of any of the following medications within14 days or at least five half lives have not been passed between last dose of the previous medication and first dose of the study medication, preceding enrolment including but not limited to: •Strong CYP1A2 Inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin etc.).
- •â€¢CYP2D6 and CYP3A4 Inhibitors(e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline etc).
- •â€¢CYP1A2 and CYP3A4 Inducers (e.g. carbamazepine, phenytoin, St. John’s wort, and rifampin etc) •Medications known to prolong the QTc interval (e.g. specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, thioridazine, mesoridazine, droperidol, and pimozide), specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class IIIantiarrhythmics (e.g., amiodarone, sotalol), and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus) •Substances known to have a substantial potential for causing agranulocytosis and lowering the seizure threshold •Lithium •Anticholinergic drugs Note: Any drug which induces or inhibits CYP 1A2, 2D6 or 3A4 should be restricted medication.
- •This list is as per the drugs which affect the metabolism of the test product and may affect the primary objective of the trial.
- •This is not an exhaustive list but guidance.
- •If other drug therapy is required prior to or during the study, decisions shall be taken by the Investigator to continue or discontinue the patient based on the following: a)The pharmacology and pharmacokinetic of the non-study medication.
- •b)The likelihood of a drug–drug interaction, thereby affecting the pharmacokinetic comparison of study medicine.
- •Prescribing Information of Clozaril® should be referred to assess the possibility of such interactions.
- •c)The time and duration of administration of the non-study medicine 19.Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery.
- •20.Patients with known positivity for human immunodeficiency virus (HIV), HBsAg or HCV.
- •21.Chronic Smokers who smokes greater than or equal to 10 cigarettes or equivalent per day.
- •22.History of difficulty with donating blood or difficulty in accessibility of veins.
- •23.Compliance with outpatient medication schedule not expected as per Principal investigator’s opinion.
- •24.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product for the current study.
- •26.Any condition/ Abnormal baseline findings that in the investigators’ judgment might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to obtain the objective of the study e.g. low expectation of compliance to dosing or expected changes in concomitant medication that may interfere in study.
结局指标
主要结局
To demonstrate the bioequivalence at steady state of Clozapine tablets 25 mg of Changzhou Pharmaceutical Factory, China vs. Clozaril® 25 mg Tablets, distributed by: Novartis Pharma Corporation East Hanover, NJ 07936 in adult schizophrenic patients already receiving stable daily dose of Clozapine 25 mg tablet twice daily under fasting conditions.
时间窗: A total of 34 blood samples will be collected during the study for PK analysis. The pre-dose blood sample of 4.0 mL (00.00) will be scheduled to be collected within 5 minutes before morning dosing on days 8, 9, 10 and days 18, 19, 20 of the study. On day 10 & day 20, the post-dose blood samples of 4.0 mL each will be drawn at 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 hrs following morning drug administration.
次要结局
未报告次要终点
研究者
研究点 (2)
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