CTRI/2015/04/005681 [Registered on: 08/04/2015] Trial Registered Prospectively
Last Modified On:
27/11/2015
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Pharmacokinetic Bioequivalence Study of Felbamate Tablet 600 mg in Adult Epilepsy Patients under Fasting Condition.
Scientific Title of Study
An Open-Label, Randomized, Two-Period, Two-Treatment, Two-Sequence, Multi-dose, Steady State, Crossover, Multicentre, Bioequivalence Study of Felbamate Tablet 600 mg of Cadila Healthcare Ltd. and Felbatol® (felbamate) Tablet 600 mg of MEDA Pharmaceuticals in Adult Epilepsy Patients under Fasting Condition
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CRL051414, Version 1.0 Date 02 June 2014
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Felbamate Tablet 600 mg of Cadila Healthcare Ltd.
Each patient will receive Comparator or Intervention product Oral tablets at
their present stable dose (1800 or 3600 mg/day) divided in three doses (i.e. one or
two felbamate 600 mg tablets every 8 hourly) for the period of 10 days in each period as per randomization schedule.
Comparator Agent
Felbatol®
Felbatol® (felbamate) Tablet 600 mg of MEDA Pharmaceuticals.
Each patient will receive Comparator or Intervention product Oral tablets at
their present stable dose (1800 or 3600 mg/day) divided in three doses (i.e. one or
two felbamate 600 mg tablets every 8 hourly) for the period of 10 days in each period as per randomization schedule.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Males or non pregnant or non lactating females aged between ≥18 to ≤ 65 years with epilepsy
2. Patients who are receiving multiples of 600 mg tablets of felbamate per day (Dose: 1800 or 3600 mg/day in three divided doses) in stable dose as monotherapy or adjunctive therapy since at least 14 days prior to randomization
3. Willing to provide written informed consent to participate in this study
4. Able to comply with protocol requirements and assessments
5. Patients with Body Mass Index (BMI) greater than or equal to 18 but less than or equal to 30. BMI values should be rounded to the nearest integer. (e.g. 30.4 rounds down to 30, while 17.5 rounds up to 18)
ExclusionCriteria
Details
1. History of hypersensitivity to felbamate or any component of the formulation
2. Patients with history of any psychiatric illness, depression, suicidal thoughts or behavior
3. Two-fold increase in the highest, 2-day pre-study seizure frequency during stabilization period
4. Single generalized, tonic-clonic seizure during stabilization period, if none occurred during past 2 months
5. Significant prolongation of generalized, tonic-clonic seizures during stabilization period
6. History of any clinical condition which may affect the absorption and metabolism of the drug e.g. ulcerative colitis or gastrointestinal disease
7. Major surgery to the gastrointestinal tract, the liver or kidney 6 months prior to randomization which may affect the pharmacokinetics of Felbamate
8. Abnormal hematologic function defined as -
 Neutrophils ≤ 1500 cells/mm3
 Platelet count ≤100,000/mm3
 Hemoglobin ≤ 10 g/dL
9. Impaired hepatic function (serum bilirubin, transaminases or alkaline phosphatase ≥ 2 times the upper limit of normal).
10. Moderate or severe renal disease.
11. Patients who are immunodeficient or have a history of immunodeficiency.
12. Consumption of grapefruit, grapefruit-like or grapefruit containing products within 7 days of drug administration.
13. Ingestion of any alcoholic, caffeine or xanthine containing food or beverage within the 48 hours prior to the initial dose of study medication.
14. Use of enzyme-modifying drugs within 30 days prior to receiving the first dose of study medication (listed in Appendix-II). They can be allowed depending on Principal Investigator’s discretion in consultation with Medical monitor, if they are kept constant in the last 30 days and are expected to remain constant during the study period.
15. A positive test result for Hepatitis (includes subtypes B & C), HIV and/or Syphilis (RPR/VDRL)
16. Patients with history of alcoholism or drug abuse within last 6 months prior to screening
17. Smokers, who smoke more than or equal to 10 cigarettes per day or more than or equal to 20 biddies per day or those who cannot refrain from smoking during study period.
18. Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 60 days.
19. Participation in any other investigational drug study within 30 days prior to randomization
20. History of any significant cardiovascular, renal, hepatic, neurologic, endocrine dysfunction, inflammatory bowel disease or any other condition which in the opinion of the investigator, may put the patient at risk because of participation in the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Cmaxss, Cminss, AUCtau, Tmaxss, Cav, % Fluctuation, % and Swing will be calculated
NIL
Secondary Outcome
Outcome
TimePoints
NIL
NA
Target Sample Size
Total Sample Size="30" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
The
sponsor has developed the test formulation. This study is being conducted to
compare the bioavailability and characterize the Pharmacokinetic profile to
evaluate the pharmacokinetic bioequivalence of Felbamate Tablet 600 mg of
Cadila Healthcare Ltd., India and Felbatol® (felbamate) Tablet 600 mg of MEDA
Pharmaceuticals and to monitor safety in
Male and Non pregnant, non-lactating female epilepsy patients already
established on felbamate monotherapy or adjunctive therapy to assess the
bioequivalence. There are very few felbatol® associated cases of aplastic anemia
and very little information is available regarding its occurrence and related
deaths. Aplastic anemia can occur within few weeks to months after starting
Felbatol® therapy. The patients who are discontinued from felbatol® remain at
risk for developing anemia for a variable and unknown period afterwards. The
most common adverse reactions seen in association with Felbatol® (felbamate) in
adults are loss of appetite, vomiting, sleeplessness, nausea, dizziness,
sleepiness and headache.
Objective: To evaluate the
pharmacokinetic bioequivalence of the test and reference products and to
monitor safety of the patients.
The total number of patients to enroll is
around 30 from India.