A Randomized, Open-Label, Two-Period, Two-Treatment, Two-Sequence, Crossover, Multiple-Dose, Steady State, Multicenter, Bioequivalence Study of Vigabatrin Tablet USP 500 mg of Zydus Worldwide DMCC, United Arab Emirates with Sabril® (Vigabatrin) Tablet 500 mg of Lundbeck, Deerfield, IL 60015, USA in Subjects with Refractory Complex Partial Seizures Under Fasting Condition.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 5
- 主要终点
- 2. Concentration at the end of the dosing interval.
研究概览
简要总结
This is a Randomized, Open-Label, Two-Period, Two-Treatment,Two-Sequence, Crossover, Multiple-Dose, Steady State, Multicenter,Bioequivalence Study in comparison between Test product and Reference product.
Study objective is 1) To evaluate the bioequivalence ofVigabatrin tablet USP 500 mg of Zydus Worldwide DMCC, United Arab Emirates withSabril® (Vigabatrin) tablet 500 mg of Lundbeck, Deerfield, IL 60015, USA inadult subjects with refractory complex partial seizures under fastingcondition. 2) To monitor safety ofsubjects.
Male or non-pregnant or non-lactating female aged between ≥ 18to ≤ 55 years with refractory complex partial seizures will be considered forthe study. Patient will be instructed to take Oral dose of either the testproduct or reference product 500 mg in the morning and evening (i.e. twice daily)at an interval of at least 12 hours (± 30 minutes*) between the doses as per therandomization schedule from Day 1 to Day 4 in each period.
* Note: This window period of study drug administration willnot be applicable if the subject is atstudy site.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 18.00 Year(s) 至 55.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or non-pregnant or non-lactating female aged between ≥ 18 to ≤ 55 years with refractory complex partial seizures.
- •The subject has refractory complex partial seizure as evidenced by the attainment of all the following criteria: a) The subject has failed because of lack of efficacy with 2 or more antiepileptics administered as monotherapy or polytherapy.
- •b) The subject should be taking at least 1 AED (A vagal nerve stimulator is not counted as an AED) 3) Currently stable on a regimen consisting of Vigabatrin tablet 500 mg twice daily for at least 28 days as adjunctive therapy and likely to continue the same dose in the study.
- •Subject with Body Mass Index (BMI) ≥ 18 to ≤ 30kg/m
- •BMI values should be rounded to the nearest integer (e.g. 30.4 rounds down to 30, while 17.5 rounds up to 18).
- •Subject with adequate hematopoietic and liver function defined as: a) Hemoglobin of ≥ 9.0 g/dL b) Platelet count ≥ 100,000/mm3 c) AST and ALT ≤ 3 times ULN, Alkaline phosphatase ≤ 2.5 times ULN, Bilirubin ≤ 1.5 times ULN.
- •Subject with a estimsted creatinine clearance of > 80 mL/min.
- •Subject with clinically non-significant findings on ophthalmologic assessments for visual field and visual acuity.
- •Male and female subjects must agree to use acceptable contraceptive methods from screening to end of study.
- •Willing to provide informed consent to participate in this study.
- •Able to comply with protocol requirements and assessments.
排除标准
- •History of hypersensitivity to Vigabatrin or any ingredients of the formulation.
- •Pre-existing ocular or neurological disease that might affect bilateral visual field or interference with perimetry (e.g. aphakia, visually significant cataract, glaucoma, diabetic retinopathy, ischemic optic neuropathy, multiple sclerosis).
- •Concurrent exposure to medication with known or suspected retinal or optic nerve toxicity (e.g. deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol).
- •Presence of primary generalized epilepsy or seizures, such as absence seizures and/or myoclonic epilepsy.
- •Subject with peripheral neuropathy.
- •Presence or previous history of Lennox-Gastaut syndrome.
- •A history of status epilepticus within approximately 6 months prior to randomization.
- •A history of psychogenic seizures.
- •Suffering from psychotic disorder(s) and/or unstable recurrent affective disorder(s) evident by use of antipsychotics within the last 2 years.
- •Expected changes in concomitant medications during the period of study.
- •Ingestion of any alcohol or alcoholic food, caffeine or xanthine containing food or beverage, recreational drugs within the 48 hours prior to first dosing of Day 1 of period I.
- •Consumption of red wine, seville oranges, grapefruit or grapefruit juice, (pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices) within 7 days prior to first dosing of Period I.
- •Presence of a progressive central nervous system CNS disease,including degenerative CNS diseases.
- •Major surgery of the gastrointestinal tract, the liver or kidney within 6 months prior to randomization which may affect the pharmacokinetics of Vigabatrin.
- •Subject unable to swallow orally administered medication or with gastrointestinal disorders likely to interfere with absorption of the study medication.
- •A positive test result for Hepatitis (includes subtypes B & C), HIV and/or Syphilis (RPR/VDRL).
- •Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 60 days or difficulty in accessibility of veins.
- •Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
- •History of any significant cardiovascular, renal, hepatic, neurologic, endocrine dysfunction, inflammatory bowel disease, cancer, or any other condition which in the opinion of the investigator, may put the subject at risk because of participation in the study.
- •Any other condition that, in the investigator’s judgment, might increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
结局指标
主要结局
2. Concentration at the end of the dosing interval.
时间窗: In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample. | In each period, on Day 4 (morning), total 16 venous blood samples will be collected | at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
5. The Average concentration at steady state during a dosing interval
时间窗: In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample. | In each period, on Day 4 (morning), total 16 venous blood samples will be collected | at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
To Analyze Pharmacokinetic parameters.
时间窗: In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample. | In each period, on Day 4 (morning), total 16 venous blood samples will be collected | at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
1. AUC during a dosage interval at steady state.
时间窗: In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample. | In each period, on Day 4 (morning), total 16 venous blood samples will be collected | at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
3. Maximum measured plasma concentration at steady state.
时间窗: In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample. | In each period, on Day 4 (morning), total 16 venous blood samples will be collected | at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
6. Degree of Fluctuation
时间窗: In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample. | In each period, on Day 4 (morning), total 16 venous blood samples will be collected | at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
7. Swing
时间窗: In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample. | In each period, on Day 4 (morning), total 16 venous blood samples will be collected | at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
4. The time to maximum plasma concentration at steady state
时间窗: In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample. | In each period, on Day 4 (morning), total 16 venous blood samples will be collected | at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
次要结局
- Not Applicable(Not Applicable)