A Multicentric, Open Label, Balanced, Randomized, Two-Period, Two Sequence, Crossover, Steady State, Food Effect Study of Clozapine Extended Release Capsule 200 mg Once Daily (Test drug, Intas Pharmaceuticals Limited, India) After Multiple Dose Administration in Adult Schizophrenic Patients Under Fasting and Fed Condition.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 92
- 试验地点
- 10
- 主要终点
- Characterization and Comparision of the Pharmacokinetic Profile of Clozapine Extended
研究概览
简要总结
Clozapine, a dibenzodiazepine derivative with potent antipsychotic properties, is indicated for the management of patients with severe schizophrenia who fail to respond adequately to at least two different antipsychotic drug treatments. In this study, the steady state pharmacokinetics and food effect of clozapine ER capsules of Intas Pharmaceuticals Limited, India (test formulation) will be assessed after multiple dose administration to adult, schizophrenic patient in a crossover design study. The Sponsor has developed an extended release formulation of clozapine. This formulation being extended release formulation, it is expected to improve the compliance, reduce drug free interval and reduce side effects which is very important considering schizophrenic population. This study is being conducted to characterize and compare the pharmacokinetic profile of the Sponsor’s formulation clozapine extended release capsule 200 mg (Test drug, Intas Pharmaceuticals Ltd., India) when administered once daily under fasting and fed condition. As a high number of healthy Patients experienced serious adverse effects after administration of antipsychotics such as hypotension, tachycardia etc., hence, regulatory authorities are recommending that studies should be conducted on Schizophrenic patients. The study is being conducted on schizophrenic patients, who are on a stable dose of clozapine, and the patients cannot be deprived of the clozapine while on treatment, the study has been planned to be a continuous administration of the test formulation without any intervening washout period.
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 60.00 Year(s)（—）
- 性别
- All
入选标准
- •Written informed consent for participation in the study by the patient and Patient Legally Acceptable Representative (LAR).
- •Patient has a documented clinical diagnosis of schizophrenia according to DSM 5 at least six months prior to screening.
- •Patients have a diagnosis of treatment-resistant schizophrenia (Treatment resistance is the failure to respond to two or more antipsychotic medications given in therapeutic dose for atleast six weeks).
- •Male and female patients between 18 and 60 years of age (both inclusive).
- •Non-smokers.
- •Male patients with weight ≥ 50 kg and female patients with weight ≥ 45 kg.
- •Not having any significant diseases or clinically significant abnormal findings except schizophrenia during screening-including medical history, physical examination, laboratory evaluations, 12-lead ECG and X-ray chest (posteroanterior view) recording, ophthalmic examination etc.
- •which is likely to adversely affect patient safety by participating in the study or study objectives in investigator opinion.
- •The investigator must ensure that the respective hepatic, renal, haematopoietic, cardiac and respiratory functions are appropriate to include the patient in the study.
- •Patients have been on a daily stable dose of 200 mg clozapine formulation for at least 3 month prior to screening visit.
- •Able to comply with study procedures in the opinion of the investigator.
- •In case of Male patients: Either partner or patient must use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
- •Cessation of birth control after this point should be discussed with a responsible physician.
- •Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug administration] sexual partner) for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
排除标准
- •Patient with known hypersensitivity/ intolerance to clozapine or any other component of the drug.
- •Clinically symptomatic orthostatic hypotension.
- •Note: Orthostatic hypotension is defined as a drop in systolic blood pressure of 20 mm Hg or more and/or a drop in diastolic blood pressure of 10 mm Hg or more on standing.
- •Concurrent use of antihypertensive medication or any medication that might predispose to orthostatic hypotension.
- •Supine blood pressure less than 110/70 mm Hg or pulse rate less than 60 or more than 100 beat per minute at screening and Day
- •An absolute neutrophil count <1500/μL performed at the screening and a day prior to randomization.
- •A history of granulocytopenia, agranulocytosis or myeloproliferative disorders (drug-induced or idiopathic).
- •A history of epilepsy or risk for seizures, paralytic ileus, or multiple syncopal episodes.
- •A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of clozapine.
- •Known case of poor metabolizer individuals with reduced activity of cytochrome P450 enzymes particularly, 1A2, 2D6 and 3A
- •Ingestion of any restricted medication at any time within 07 days before the first study drug administration.
- •Smokers, or who have smoked within last six months prior to start of the study.
- •Positive tests for drug or alcohol abuse at screening and baseline.
- •A history of alcohol or drug dependence by Diagnostic and Statistical Manual of Mental Disorders V (DSM 5) criteria during the 6-month period immediately prior to study entry.
- •Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of study medication or during the study.
- •Receipt of an investigational medicinal product or participation in a drug research study within 90 days prior to receiving the first dose of study medication or during the study.
- •A known case of or positive test for HIV infection or hepatitis B or HCV.
- •Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption.
- •Psychosis judged to be the direct physiological effect of an abused medication or substance.
- •Hospitalisation for an exacerbation of schizophrenia within two months prior to screening and during the screening period.
- •Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others.
- •Patients with the following cardiac conditions are excluded: a.
- •Recent myocardial infarction (<12 months).
- •History of QTc prolongation or using concomitant medications which prolong QTc interval.
- •First-degree heart block with PR interval > 0.22 seconds.
- •Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia.
- •Uncompensated congestive heart failure, myocarditis, cardiomyopathy.
- •Complete left bundle branch block.
- •Presence of narrow angle glaucoma assessed by tonometry.
- •Patients with uncontrolled diabetes mellitus or fasting blood glucose ≥ 126 mg/dl at screening visit.
- •Patient with hyperprolactinemia at screening visit which as judged by Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial.
- •Dementia related psychosis.
- •Concurrent use of other drugs known to suppress bone marrow function.
- •Pregnant or lactating females.
- •A history of risk for seizures.
- •Compliance with outpatient medication schedule not expected.
- •Expected changes in concomitant medications during the period of study.
结局指标
主要结局
Characterization and Comparision of the Pharmacokinetic Profile of Clozapine Extended
时间窗: Pre-dose blood sample | Day 07, Day 08, Day 09, Day 10, Day 17, Day 18, Day 19 and Day 20 | Post-dose blood sample | 0.500, 1.000, 1.500, 2.000, 2.500, 3.000, 3.500, 4.000, 4.500, 5.000, 5.500, 6.000, 6.500, 7.000, 7.500, | 8.000, 9.000, 10.000, 12.000, 14.000, 16.000, 20.000 and 24.000 hours of dosing.
Release Capsule 200 mg When Administered Once Daily Under Fasting and Fed Condition.
时间窗: Pre-dose blood sample | Day 07, Day 08, Day 09, Day 10, Day 17, Day 18, Day 19 and Day 20 | Post-dose blood sample | 0.500, 1.000, 1.500, 2.000, 2.500, 3.000, 3.500, 4.000, 4.500, 5.000, 5.500, 6.000, 6.500, 7.000, 7.500, | 8.000, 9.000, 10.000, 12.000, 14.000, 16.000, 20.000 and 24.000 hours of dosing.
次要结局
- Safety of the patients(Through out the study)