A Multicentric, Open Label, Randomized, Two-Treatment, Two-sequence, Two-period, Cross-over, Multiple dose, Steady-state Clinical Bioequivalence Study of Clozapine Tablets USP 100 mg of Alkem Laboratories Limited, India (Test) with CLOPINE® 100 mg (Clozapine) tablets, Hospira Australia Pty Ltd (Reference) in Patients with Schizophrenia under Fasting conditions.
试验速览
- 阶段
- 1/2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 3
- 主要终点
- AUC0Ï„ Area under the plasma concentration time curve over the steady state dosing interval.
研究概览
简要总结
A Multicentric, Open Label, Randomized, Two-Treatment, Two-sequence, Two-period, Cross-over, Multiple dose, Steady-state Clinical Bioequivalence Study of Clozapine Tablets USP 100 mg of Alkem Laboratories Limited, India (Test) with CLOPINE® 100 mg (Clozapine) tablets, Hospira Australia Pty Ltd (Reference) in Patients with Schizophrenia under Fasting conditions.
AUC0-τ: Area under the plasma concentration – time curve over the steady state dosing interval.
Cmax-ss: Maximum concentration over the steady state dosing interval.
Cmin-ss: Minimum concentration over the steady state dosing interval.
Cavg-ss: Average concentration over the steady state dosing interval.
Percentage fluctuation: [Cmax-ss – Cmin-ss / Cavg-ss] *100
Tmax-ss: Time of maximum measured plasma concentration over the steady state dosing interval.
Cpd (pre-dose concentration)-Pre-dose concentrations determined before a dose at steady state.
Safety and tolerability as assessed by reported adverse events, laboratory and clinical investigations, and vital signs
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 55.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patient diagnosed with a) treatment-resistant schizophrenia or; b) schizophrenia, chronic (all types) and in a residual phase or in remission, or schizoaffective disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria.
- •2.Patient with Body mass index between 18.5 to 30 kg/m2 (both inclusive) and aged between 18 to 55 years (both inclusive).
- •3.Patient is on for Clozapine therapy and has been taking a stable dose of Clozapine Tablets 100 mg twice daily for at least three months before enrolment in the study.
- •4.Patient having adequate hematologic reserve at screening as per principal investigator assessment.
- •5.Patient having adequate and stable hepatic function and renal function at screening as per principal investigator assessment.
- •6.Patient should have no clinically significant abnormality in any of the laboratory parameters including ECG and Chest X-ray as per the discretion of Principal Investigator.
- •7.Patient and Legally Acceptable Representative had given consent after being advised of the nature and risks of the study.
- •8.Female patient of childbearing potential must have a negative serum pregnancy test at screening.
- •9.Patient agreed to use acceptable methods of birth control as directed by study team.
排除标准
- •1.History of suicidal tendencies (e.g. suicidal attempts) within the past 3 months prior to screening or immediate risk of harm to self or other at the time of Screening, as judged by the investigator.
- •2.Absolute neutrophil count ≤ 2000 /mm3 or /µL and WBC count ≤ 4000 /mm3 or /µL.
- •3.Elderly patient with diagnosed dementia related psychosis.
- •4.Patient with medical or surgical condition that might interfere with the absorption, metabolism, or excretion of Clozapine or other study medications.
- •5.Patient with history of granulocytopenia or myeloproliferative disorder, either drug-induced or idiopathic.
- •6.Patient with history of clinically significant cardiovascular, renal, hepatic, respiratory, endocrine (except noninsulin-dependent diabetes mellitus), or gastrointestinal disease.
- •7.Patient found to be positive for HIV, HBsAg or HCV.
- •8.Patient with history of epilepsy or seizures or are comatose or experiencing severe central nervous system depression.
- •9.Patient is unable to communicate with the investigator.
- •10.Patients with history of allergic reactions to Clozapine or chemically related psychotropic drugs.
- •11.Patients having concurrent neurological diagnosis, including mental retardation, severe tardive dyskinesia, or idiopathic Parkinson’s disease.
- •12.Patients who had undergone electroconvulsive therapy within the past one month.
- •13.Patient had demonstrated clinically significant homicidal behavior within the past 12 months.
- •14.Patient had received any investigational drug within the past 90 days.
- •15.Patient had history of narrow-angle glaucoma.
- •16.Patient with known history of phenylketonuria.
- •17.Patient with known history of significant 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).
- •18.Patient with uncontrolled hypertension as per the discretion of PI 19.Patient is on concurrent use of other drugs known to suppress bone marrow function.
- •20.Patient had history of multiple syncopal episodes.
结局指标
主要结局
AUC0Ï„ Area under the plasma concentration time curve over the steady state dosing interval.
时间窗: Venous blood samples 5 mL will be withdrawn within 5 minutes prior to dosing on Day 7 8 9 17 18 19 confirm steady state condition. | On Day 10 and Day 20 venous blood samples 5mL will be collected at 0.00 5 minutes prior to morning dose and 0.25 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 7.00 8.00 10.00 and 12.00
Cmaxss Maximum concentration over the steady state dosing interval.
时间窗: Venous blood samples 5 mL will be withdrawn within 5 minutes prior to dosing on Day 7 8 9 17 18 19 confirm steady state condition. | On Day 10 and Day 20 venous blood samples 5mL will be collected at 0.00 5 minutes prior to morning dose and 0.25 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 7.00 8.00 10.00 and 12.00
次要结局
- Cminss Minimum concentration over the steady state dosing interval.(Cavgss Average concentration over the steady state dosing interval.)