A Study of the Efficacy and Safety of Topiramate as an add-on Therapy in the Treatment of Epilepsy Patients With Lennox-Gastaut Syndrome
June 2, 2011 updated by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
A Double-Blind Trial of Topiramate in Subjects With Lennox-Gastaut Syndrome.
The purpose of this study is to evaluate the effectiveness and safety of topiramate as add-on therapy in the treatment of epilepsy patients with Lennox-Gastaut syndrome, a severe form of epilepsy in which there are mixed types of seizures.
Study Overview
Detailed Description
Lennox-Gastaut syndrome is a severe form of epilepsy that usually develops in children 4 years of age and younger.
It is characterized by several seizure types and developmental delay.
Tonic seizures, in which the muscle tone is greatly increased and body, arms and legs make sudden stiffening movements, is particularly common in Lennox-Gastaut syndrome.
Although atonic seizures, in which there is a sudden loss of muscle tone and strength, can occur in individuals with this syndrome.
Control of seizures is difficult because they are usually resistant to antiepileptic drugs.
Topiramate is a drug that is currently widely used for the treatment of seizures in adults and pediatric patients (2 to 16 years of age).
This is a randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of topiramate as an add-on therapy in patients with Lennox-Gastaut syndrome.
The study is composed of two phases: baseline (28 days) and double-blind treatment (approximately 11 weeks).
Patients or their guardians/parents are given diaries to record information on seizures occurring during the study.
During the baseline phase, the patient continues to receive the antiepileptic drug they have been taking.
The double-blind phase is divided into two periods: titration, in which the topiramate dose was gradually increased (21 days) (patient's antiepileptic drug continues; this dose remains the same) and maintenance (56 days).
The dose of both topiramate and the patient's antiepileptic drug remain constant during the maintenance period.
Based on the investigator's judgment, all patients completing the double-blind period could be enrolled into an extension phase of the study.
The primary assessment of effectiveness is the percent reduction from baseline in seizure rates (all types of seizures) in the double-blind phase.
Safety assessments include the frequency of adverse events, results of clinical laboratory tests (hematology, biochemistry, and urinalysis), measurements of vital signs and body weight, physical examination and electrocardiogram findings, and neurological examinations.
The study hypothesis is that topiramate is superior to placebo in reducing the seizure rate from baseline in the double blind phase of the study and is well tolerated.
Topiramate (25milligram [mg] or 100mg tablets) or placebo, taken by mouth, starting at a dose of 1mg/kilogram(kg)/day, gradually increasing over 3 weeks to a total dose of 6mg/kg/day (given twice daily in equal oral doses for 8 weeks).
Maximum daily dose is <=600mg/day.
Study Type
Interventional
Enrollment (Actual)
100
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 30 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Body weight of at least 25 pounds
- diagnosis of Lennox-Gastaut syndrome and an electroencephalogram (EEG) with an abnormal pulsation pattern
- atypical absence seizures and drop attacks (i.e., tonic-atonic seizures) among other seizure types that could include tonic-clonic, myoclonic, and minor-motor
- at least 60 seizures during the month before baseline
- must be maintained on 1 or 2 antiepileptic drugs
- females must not have had their first menstrual period, or are physically incapable of child bearing, or if of child bearing potential, sexually abstinent, or using adequate contraceptive measures, and have a negative pregnancy test before study entry.
Exclusion Criteria:
- Patients whose seizures are due to a progressive disease (for example, active infection, cancer or metabolic disturbance)
- have a significant recent history (within 2 years) of medical diseases (respiratory, heart, gastrointestinal, blood diseases, rheumatic fever or cancer)
- history of alcohol or drug abuse.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
|---|
|
Percent reduction from baseline in seizure rates (all types of seizures) in the double-blind phase. Percent reduction in drop attacks (tonic-clonic) and parent/guardian global evaluation at end of study
|
Secondary Outcome Measures
Outcome Measure |
|---|
|
Percent treatment responders all types of seizures. Percent treatment responders drop attacks (tonic-clonic seizures). Safety evaluations conducted throughout the study.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4.
- Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group. Neurology. 1999 Jun 10;52(9):1882-7. doi: 10.1212/wnl.52.9.1882.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 1993
Study Completion (Actual)
February 1, 2001
Study Registration Dates
First Submitted
October 7, 2005
First Submitted That Met QC Criteria
October 7, 2005
First Posted (Estimate)
October 12, 2005
Study Record Updates
Last Update Posted (Estimate)
June 3, 2011
Last Update Submitted That Met QC Criteria
June 2, 2011
Last Verified
January 1, 2011
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CR005464
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.