Three way, three period, cross over bioequivalence study of single oral dose of three brands of 300mg Phenytoin sodium tablets marketed in India, on healthy Indian human volunteers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- To calculate pharmacokinetic parameters such as Cmax, tmax, AUC0-t and compare it with comparator drugs
研究概览
简要总结
Most antiepileptic drugs (AEDs) have a narrowtherapeutic index, and have a highpotential for CNS-related adverse events, which is usually related to the serum concentration of the drug. There is no scientificevidence, as of now to predict that the20% variability in bioavailabilty recommended by guidelines can be tolerated by patients withepilepsy. Dosage adjustment is required to provide optimal seizurecontrol while avoiding adverse drug effects. The titration of dose ofantiepileptic drugs is guided by target dose, plasma drug concentrationreference range or seizure response. In the individual patient the range ofeffective and tolerable antiepileptic drug dose or plasma drug concentration isoften not known. Management regimens may become very complex, with titration sometimestaking weeks in order to avoid adverse effects. Patients need their medicationto be consistent during titration so that prescribed changes of dose havepredictable consequences.
Phenytoin is poorly soluble in physiological fluids,and its bioavailability is therefore strongly influenced by various factors,particularly particle size and the substances used as excipients in theformulation. In designingformulations, there are three pharmacologic risk factors- low water solubility,a narrow therapeutic index and non-linear pharmacokinetics. Generic drugs contain theidentical active ingredient(s) as the innovator medicine drug however theexcipients (inactive ingredients) may vary. The rate and extent of absorptionor bioavailability often differs between different generic versions of brandedproducts, and each differs from the branded formulation itself, which can have serious effects for that patient.For example, a slight increase in phenytoin bioavailability can lead to amarked increase in serum level and thus to adverse effects, especially when thelevel is more than 15mg/L. Furthermore,nonlinear pharmacokinetics (e.g., phenytoin, PHT) and protein binding (e.g.,valproate, VPA) can amplify even slight differences in bioavailability
In India, there have been very limitedstudies in this direction. One study reported is comparison in the bioavailability of a single oral 200-mg dose of four brands ofphenytoin sodium available in the Indian market; the results of the study revealed that one brand was bioinequivalent.Other comparisons indicate but do not prove bioinequivalence of the otherbrands. Study concludes that in Indiaswitching phenytoin brands could have significant implications and is notadvisable once a patient is carefully titrated on one formulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- Male
入选标准
- ••Weight range within 20% of the ideal body weight as per standard tables and Indian criteria.
- ••Age 18-45 years of male gender only.
- ••Patients willing to sign informed consent form before undergoing screening.
- ••Patients willing to undergo follow up for 2 – 6 months.
- ••Physical examination – all findings of physical examination are normal with no ongoing serious illness that may affect the outcome of the study.
- ••Biochemical and hematologic test values (done within 2 week of the study), urine examination, and ECG—all within normal limit •Negative for Hbs Ag (Australia antigen) and HIV •Agreement to abstain from caffeine on the day of the study and from alcohol and any other medication for 48 hours prior to entry into the study and during the course of the study.
排除标准
- ••History of intercurrent or concurrent diseases chronic alcohol consumption or drug addiction.
- ••History of chronic GI, renal, hepatic, cardiovascular, CNS, respiratory, infectious, or psychiatric diseases that affect the outcome of the study, •History of allergy or hypersensitivity to phenytoin sodium, consumption of tobacco in any form, participation in a new drug study in the past 6 months and in a bioavailability or any study of a marketed drug in the past 3 months, donating blood in the past 3 months, •Any drug intake in the past 15 days or intake of an enzyme-inducing agent in the past 30 days.
结局指标
主要结局
To calculate pharmacokinetic parameters such as Cmax, tmax, AUC0-t and compare it with comparator drugs
时间窗: blood will be collected at 0,1,2,3,4,5,6,8,10,12,24,36,48,60 and 72 hours and parameters will be collected at these time points
次要结局
未报告次要终点