| CTRI Number |
CTRI/2014/05/004600 [Registered on: 15/05/2014] Trial Registered Prospectively |
| Last Modified On: |
14/08/2014 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
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Type of Study
|
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| Study Design |
Randomized, Crossover Trial |
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Public Title of Study
|
A study to compare absorption of the test drug - Tab Felbamate 600 mg with that of the approved drug - Tablet Felbatol (Felbamate 600,in patients of partial epilepsy not responding to therapy. |
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Scientific Title of Study
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A multicenter, open-label, randomised, two-treatment, twoÂsequence, cross-over, steady-state clinical bioequivalence study of Felbamate 600mg tablet of Lannett Company Inc., USA with Felbatol® 600mg tablet of Meda Pharmaceutical Inc., USA in adult epileptic (partial seizures with and without generalization) patients already established (run-in) on Felbamate as an adjunctive therapy under fasting state. |
| Trial Acronym |
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Secondary IDs if Any
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| Secondary ID |
Identifier |
| BE/13/287 Version 01 dated 27 February 2014 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Himali Gole |
| Designation |
Project Manager |
| Affiliation |
Raptim Research Ltd. |
| Address |
Raptim Resaerch Ltd.
A-226, M.I.D.C., T.T.C., Industrial Area,
Mahape, Navi Mumbai-400 701, India.
Tel.: 22 2778 1889
Telefax: 22 2778 1889
Thane
MAHARASHTRA
400701
India |
| Phone |
02227781889 |
| Fax |
02227781889 |
| Email |
himali.gole@raptimresearch.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Himali Gole |
| Designation |
Project Manager |
| Affiliation |
Raptim Research Ltd. |
| Address |
Raptim Resaerch Ltd.
A-226, M.I.D.C., T.T.C., Industrial Area,
Mahape, Navi Mumbai-400 701, India.
Tel.: 22 2778 1889
Telefax: 22 2778 1889
Thane
MAHARASHTRA
400701
India |
| Phone |
02227781889 |
| Fax |
02227781889 |
| Email |
himali.gole@raptimresearch.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Himali Gole |
| Designation |
Project Manager |
| Affiliation |
Raptim Research Ltd. |
| Address |
Raptim Resaerch Ltd.
A-226, M.I.D.C., T.T.C., Industrial Area,
Mahape, Navi Mumbai-400 701, India.
Tel.: 22 2778 1889
Telefax: 22 2778 1889
Thane
MAHARASHTRA
400701
India |
| Phone |
02227781889 |
| Fax |
02227781889 |
| Email |
himali.gole@raptimresearch.com |
|
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Source of Monetary or Material Support
|
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Primary Sponsor
|
| Name |
Lannett Company Inc |
| Address |
13200 Townsend road,
Philadelphia, PA 19154, USA
Telephone: 001-215-333-9000x2276
Fax: 001-215-671-0669
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| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
| Name |
Address |
| Raptim Reserach |
A226, TTC Industrial Area
Near Mahape Depot, Mahape MIDC
Navi Mumbai 400 701, India
Tel 912227781889
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Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DrManjari Tripathi |
All India Institute of Medical Sciences |
Room-705, 7th Floor, Department of Neurology, C.N. Center, All India Institute of Medical Sciences,
Ansari Nagar- New Delhi 110029, India.
New Delhi
DELHI |
011-26494494
manjaritripathi1@gmail.com |
| Dr Sanjay Ramteke |
Brain Clinic, Jasleen Hospital |
Opp. Big Bazar, 1st Floor, Panchsheel square, Dhantoli, Nagpur- 440012
Nagpur
MAHARASHTRA |
0712-2450033
0712-2421209
ssrt95@yahoo.co.in |
| Dr Suresh Gaikwad |
Critical Care Center Pvt. Ltd. |
31, Reshim Bagh, Sakkardara, Umrer Road, Nagpur- 440009
Nagpur
MAHARASHTRA |
9823018361
gaikwadhospital@ymail.com |
| Dr Turaga Surya Prabha |
Nizams Institute of Medical Sciences |
Department of Neurology, Nizams Institute of Medical Sciences, Punjagutta, Hyderabad - 500082
Hyderabad
ANDHRA PRADESH |
09246589899
914023370899
surmukh99@gmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee - All India Institute of Medical sciences, Dr. Manjari Tripathi |
Approved |
| Jasleen Hospitals Ethics Committee, Dr. Sanjay Ramteke |
Approved |
| Jasleen Hospitals Ethics Committee, Dr. Suresh Gaikwad |
Approved |
| NIMS Institutional Ethics Committee |
Submittted/Under Review |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Refractory Epilepsy, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Felbamate Tablets 600 mg |
Manufactured by: Lannett Company Inc., USA
Tab Felbamate 600 mg will be given in the PK phase, as one tablet thrice a day for 10 days in Period I and II (total 20 days) as per the randomization codes. |
| Comparator Agent |
FELBATOL® (Felbamate) Tablets 600 mg |
Manufactured by: Meda Pharmaceuticals Inc. USA
Tab Felbatol 600 mg will be given to the subjects in three phases as given below.
1. Up-titration and stabilization phase:Tab Felbatol 600 mg will be given once a day for the first week, twice a day for the second week and thrice a day for the third week and fourth week (stabilization period).
2. Pharmacokinetic (PK) Phase: Tab Felbatol 600 mg will be given thrice a day for 10 days in period I and II (total 20 days)as per the randomization codes.
3. Down-titration phase: Tab Felbatol 600 mg will be given twice a day for the first 7 days following the PK phase, then once a day for 7 days and if required will be substituted with Felbatol 400mg once a day for 7 days and then stopped.
At the time of decreasing the dose of Felbatol, other anti-epileptic drugs will be started as per the investigators discretion.
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Inclusion Criteria
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| Age From |
18.00 Year(s) |
| Age To |
45.00 Year(s) |
| Gender |
Both |
| Details |
The patients who fulfill all the following inclusion criteria will be included:
i. Patients should be in the range of 18 - 45 years of age (both inclusive).
ii. BMI should be in the range of 18.5 to 24.9 Kg/m2 for male volunteers and 18.0 to 27.9 Kg/m2 for female volunteer’s (both inclusive).
iii. Patients having refractory partial seizures with and without generalization not controlled on standard antiepileptic drugs at therapeutic levels
iv. Patients with normal findings as determined by baseline history, physical examination and vital signs (blood pressure, pulse rate, respiratory rate and axillary temperature).
v. Patients with normal/ not significant laboratory values as determined by hematological tests, biochemistry, urine analysis and ECG in correlation with clinical findings.
vi. Willingness to follow the protocol requirement as evidenced by written informed consent.
vii. Agreeing to, not using or conforming to not having used any medication (prescription and over the counter), including vitamins and minerals for 15 days prior to study & during the course of the study.
viii. No history or presence of significant alcoholism.
ix. No history of drug abuse.
x. Non-smokers, ex-smokers and moderate smokers will be included. ‘Moderate smokers’ are defined as those who smoke 10 cigarettes or less per day, ‘Ex-smokers’ are those who stopped smoking for at least 3 months.
xi. All female patients having negative serum pregnancy test prior to enrolling into the study. All female patients who are of child bearing potential or those within the first two years of the onset of menopausal syndrome using acceptable methods of birth control at least 30 days prior to onset of screening period and till 30 days post last dose of study drug in period-II. Acceptable birth control methods include Barrier methods such as diaphragm/condom with spermicide. Unacceptable methods include oral or implanted contraceptives.
|
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| ExclusionCriteria |
| Details |
The patients meeting with any one of the following criteria should be excluded:
i. History of aplastic anemia or hepatic failure
ii. Requiring medication for any ailment having enzyme-modifying activity in previous one month, prior to drug administration day other than Felbamate
iii. History of cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological (other than refractory epilepsy), metabolic hematological, gastrointestinal, endocrine or immunological.
iv. At baseline (Prior to randomization):
 Two-fold increase in the highest, 2-day pre-study seizure frequency
 Single generalized, tonic-clonic seizure if none occurred during pre-treatment screening and/or
 Significant prolongation of generalized, tonic-clonic seizures and Status Epilepticus.
v. Participation in any other clinical study within 90 days prior to onset of screening period.
vi. History of malignancy or any other serious diseases.
vii. Any contraindication to blood sampling.
viii. Refusal to abstain from smoking or consumption of tobacco products 72.00 hours before morning drug administration on days- 10 and 20 and until after the last blood sample collection in each study period.
ix. Use of xanthine containing food or beverages (chocolates, tea, coffee or cola drinks), grapefruit juice or products containing grapefruit and alcohol and any alcoholic products, for 72.00 hours before morning drug administration on days- 10 and 20 and until after the last blood sample collection in each study period.
x. Blood donation within 90 days prior to the commencement of the study.
xi. Patients with positive HIV I and II tests, HBsAg or HCV tests.
xii. Positive urine screen for drugs of abuse and breath alcohol test done during check-in process.
xiii. Positive urine pregnancy test and serum pregnancy test for female patients done during screening and check-in process, respectively.
xiv. A history of allergic or adverse reactions to Felbamate or any comparable or similar product.
xv. A history of severe hepatic impairment, drug induced leukopenia/neutropenia, congenital prolongation of the QT interval, cardiac arrhythmias, myocardial infarction or unstable heart disease
|
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Method of Generating Random Sequence
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Computer generated randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
| To determine clinical bioequivalence of Felbamate 600mg tablet of LANNETT Company, Inc., (Test) with that of an already marketed reference formulation i.e. Felbatol® 600 mg tablet of Meda Pharmaceuticals Inc.(Reference) in 38 adult epileptic (partial seizures with and without generalization) in patients |
At the end of the Pharmacokinetic phase, that is, after completion of Period I and Period II. The PK analysis of the per protocol population will begin about 48 days (4 weeks - up-titration plus 20 days PK phase) after enrollment into the study. |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| To evaluate safety of administration of Felbamate Tablets 600 mg in refractory partial epilepsy patients stabilised on Felbamate. |
Safety monitoring will be conducted throughout the study.
Safety analysis will be carried out in the intention to treat population at the end of the down-titration phase. |
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Target Sample Size
|
Total Sample Size="38"
Sample Size from India="38"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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N/A |
|
Date of First Enrollment (India)
|
20/05/2014 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0"
Months="3"
Days="0" |
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Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
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Publication Details
|
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
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Background
Felbamate is an anti epileptic drug recommended for use in patients
with refractory partial seizures. Felbamatol 600 mg is a US
FDA approved and licensed version of Felbamate manufactured by Meda Pharmaceuticals Inc., U.S.A. The
said study will be conducted to provide pharmacokinetic data to establish the bioequivalence of
Felbamate 600mg tablets manufactured by Lannett
Company Inc., U.S.A. with Felbatol 600 mg tablet.
Type of study
A multicenter,
open-label, randomized, two-treatment, two sequence, cross-over, steady-state
clinical bioequivalence study
Sample size
Thirty eight (38) patients
with refractory partial-onset seizures with and without generalization as per
inclusion/exclusion criteria already receiving Felbamate 600mg Q8H and any of
the following mentioned drugs i.e. valproic acid, levetiracetam, gabapentin, or
pregabalin in a stable regimen for at least 7 days prior to randomization will
be enrolled.
Study duration
Except screening,
clinical up-titration (3 weeks), clinical stabilization period (1 week) and
clinical down-titration period (3weeks), the total study duration (pharmacokinetic
phase) for patient participation will be 20 days.
Safety monitoring
Throughout the study,
subject well being and safety will be monitored. At the end of the study or in case
of a patient withdrawal or termination or dropout, the following procedures will be done: Physical
examination, vital sign and well being, hematology, biochemistry and urine
analysis, 12-lead ECG, and monitoring for concomitant medication and safety.
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