A multi-center, open-label, balanced, randomized, two-treatment, two-period, two-sequence, two-way crossover, steady-state bioequivalence study of Felbamate Tablets 600mg of Lannett Company Inc., USA with FELBATOL® (Felbamate) Tablets 600mg of MEDA Pharmaceuticals Inc., USA among adult epilepsy (partial seizures with or without generalization) subjects already established on a stable adjunctive therapy.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 4
- 主要终点
- The primary objective of the study is to assess whether the test product is bioequivalent to reference product based on the evaluation of Cmax,ss and AUC0-Ï„,ss
研究概览
简要总结
Felbamate (2-phenyl-1,3-propanediol dicarbamate) is achemically unique antiepileptic agent.
The purpose of this study is to establish Bioequivalencebetween Felbamate Tablet 600 mg of of Lannett Company Inc., USA with Felbatol®(Felbamate) Tablet 600 mg of MEDA Pharmaceuticals in Adult Epilepsy Patients(partial seizures with or without generalization) subjects already establishedon a stable adjunctive therapy under Fasting Conditions.
Thisstudy will be initiated only after obtaining the approvals from Drug ControllerGeneral of India (DCGI) and from Institutional Ethics Committee (IEC) of participatingsites.
Subjectsqualifying inclusion and exclusion criteria will undergo up-titration from onetablet of 600mg Reference Felbamate to 3 tablets of 600mg Reference Felbamate 8hrs apart over a period of 3 weeks followed by stabilization phase wheresubject will receive 3 tablets of 600mg Reference Felbamate 8 hrs apart for aweek.
Uponsuccessful completion of stabilization phase, subject will be randomized toTest or Reference 600mg Felbamate to be taken 8 hrs apart for 10 days followedby cross-over of Test or Reference 600mg Felbamate to be taken 8 hrs apart foranother 10 days. Randomization will happen as per site specific randomizationschedule.
Subjectwill be check-in on Day-7 and Day-17. On Day-8, Day-9, Day-10, Day-18, Day-19and Day-20 pre-dose PK sample will be taken. Apart from these samples, onDay-10 and Day-20 post dose PK samples will be taken at below given timepoints:
0.25,0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.00, 5.00, 6.00and 8.00 hrs post morning dose
Subjectwill be discharged on Day-10 and Day-20 after completion of PK samples.
PostDay-20, down-titration with 600mg Reference Felbamate Tablet will start fromtwo tablets per day for a week to one tablet per day for a week.
Bioanalysis:Plasma samples will be analyzed for Felbamate using a validated analyticalmethod in accordance with USFDAGuidelines and in-house SOPs of bioanalytical laboratory.
PKparameters and their evaluations will be performed based on:
· Primary PK parameters: Cmax,ssand AUC0- τ,ss
· Secondary PK parameters: Cmin,ss,Cavg,ss,Degree of Fluctuation, Swing and Tmax,ss.
Acceptancecriteria for steady state attainment will be based on following criteria:
· Probability value for the resultantslope should be statistically nonsignificant at 5% level of significance.
· If the probability values for theresultant slope is statistically significant at 5% level of significance, butDay 10 - 0.00 hrs / Day 10 - 8.00 hrs ratios should be within 90.00% to 111.11%in each study period.
Test product will be considered bioequivalent toreference product, if 90% CI for ratio of geometric least square means based onlog transformed primary PK parameters - Cmax,ssand AUC0- Ï„,ss fall within acceptable BE limits of 80.00% to125.00% for Felbamate.
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 45.00 Year(s)（—）
- 性别
- All
入选标准
- •A patient fulfilling all the following criteria will be included in the present study: 1)Patients willing to provide written informed consent for participation in the study; 2)Having ability to comprehend the nature and purpose of the study; 3) Willing to be available for the entire study period and to comply with protocol requirements.
- •Disease population and treatment condition – Subjects with documented clinical diagnosis of refractory partial seizures with or without generalization.Subjects with partial seizures with or without generalization not controlled with any of standard antiepileptic regimen of Sodium Valproate (or Valproic acid), Levetiracetam, Gabapentin or Pregabalin at therapeutic levels; 5)BMI in the range of 18.5 to 29.99 kg/m2 both inclusive.
- •Non-smoker or ex-smoker or mild / moderate smokers and willing to abstain from chewing or smoking any tobacco containing product at least 72.00 hrs prior to first dosing (onset of up-titration) of the study and throughout study.
- •Willing to abstain from alcohol or alcoholic products within 24.00 hrs prior to first dosing (onset of up-titration) of the study and throughout the study.
- •Willing to abstain from, xanthine or its derivative containing food or beverages (e.g. chocolates, tea, coffee or cola drinks) within 72.00 hrs prior to first prior to first sample collection in each study period and throughout the sampling points.
- •Willing to abstain from grapefruit or its juice within 72.00 hrs prior to first prior to first sample collection in each study period and throughout the sampling points.
- •Clinically non-significant serum electrolytes (sodium, potassium and chloride).
- •With normal or clinically non-significant laboratory values as determined by hematological, biochemistry tests, urine analysis.
- •With a normal or clinically non-significant 12-lead ECG.
- •In case of female subjects: • Negative urine pregnancy test during screening and, negative serum β-HCG test at baseline visits and at check-in for housing during each study period.
- •â€¢Patients with child bearing potential or those within their first two years of onset of menopausal syndrome must either abstain from sexual intercourse, or must be using acceptable methods of birth control during the study (Acceptable birth control methods include barrier methods such as diaphragm/condom with spermicide or who are surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy has been performed), but must not use hormonal contraceptive (either oral/implants)).
排除标准
- •A patient fulfilling any one of the following criteria will be excluded from the study: 1)Institutionalized patients.
- •A history of allergic or hypersensitive reactions Felbamate or other carbamates or to any of the excipients of formulation which in the opinion of an investigator, would compromise the safety of the subject or the study.
- •History of aplastic anemia or significant hematological disorder (drug induced or idiopathic).
- •History of liver failure or significant liver disease.
- •History of psychiatric illness or depression.
- •Concurrent use of other drugs known to suppress bone marrow function.
- •Liver enzyme (SGPT and SGOT) levels >2 times the upper limit of normal values at baseline and during the entire study.
- •Clinically significant drop in the red blood cells, white blood cells and platelet counts at baseline and during the entire study.
- •Subjects with any of the following seizure criteria during the study from the date of study onset (baseline): •2-fold increase in the highest, 2-day pre-study seizure frequency.
- •â€¢Single, generalized, tonic-clonic seizure if none occurred during pre-treatment screening, and/or •Significant prolongation of generalized, tonic-clonic seizures.
- •A medical or surgical condition that might interfere with the absorption, metabolism, or excretion of Felbamate during the study.
- •Significant history or current evidence of malignancy or chronic infectious, cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic (endocrine), hematological, gastrointestinal, immunological or psychiatric diseases, or organ dysfunction, which in the opinion of an investigator, would compromise the safety of the subject or the study; 13)Expected changes in the concomitant medications during the study periods.
- •Expected incompliance with outpatient medications.
- •A history of alcohol or drug dependence by DSM-V-TR criteria during the 6-month period immediately prior to study entry; 16)Positive alcohol breath or urine drug of abuse tests during randomization, or at check-in for housing during each study period.
- •Positive test for Human Immunodeficiency virus (HIV) type I/II antibodies or Hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) antibodies.
- •In case of female subjects: Planning to become pregnant Lactating or nursing subjects 19)Participated in any clinical investigation requiring repeated blood sampling, blood donation, or have blood loss of >500 mL in past 8 weeks or participated in any clinical study within the past 3 months prior to first dosing (onset of up-titration) of the study.
- •Any major illness or hospitalization within 90 days prior to first dosing (onset of up-titration) of the study.
- •History of difficulty in accessibility of veins in arms.
结局指标
主要结局
The primary objective of the study is to assess whether the test product is bioequivalent to reference product based on the evaluation of Cmax,ss and AUC0-Ï„,ss
时间窗: Median Tmax at 2.5 hours with range of 0 hrs to 8 hrs
次要结局
- Descriptive statistics for pharmacokinetic (PK) parameters - Cmin,ss, Cavg,ss Degree of(Fluctuation, Swing and Tmax,ss;)