Clobazam in Patients With Lennox-Gastaut Syndrome
- Conditions
- EpilepsyEpilepsy, GeneralizedSeizures
- Interventions
- Registration Number
- NCT00518713
- Lead Sponsor
- Lundbeck LLC
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of clobazam as adjunctive therapy in the treatment of seizures which lead to drop attacks (drop seizures) in patients 2 to 60 years of age with Lennox-Gastaut Syndrome (LGS). Patients will be enrolled at approximately 65 sites in the U.S. and ex-US for up to 23 weeks. Patients will be randomly assigned to either a low, medium or high dose, or placebo. The study will include a baseline period, a titration period and a maintenance period. After the maintenance period, patients will either continue into an open-label extension study or enter the taper period with a final visit 1 week after the last dose.
- Detailed Description
LGS poses a significant treatment challenge. No single antiepileptic drug (AED) provides satisfactory relief for all or most patients with LGS and a combination of treatments is often required. Even with combination therapy, many LGS patients show resistance to treatment. Adjunctive therapy with newer anticonvulsant medications has demonstrated efficacy for some patients, although polytherapy and high medication doses are often associated with unfavorable adverse event profiles.
More effective and better-tolerated treatment options are needed for this population of medically intractable epilepsy patients. Clobazam may provide an improved safety profile compared to other AEDs currently approved for the treatment of LGS and may have less hypotonia and drooling effects than other benzodiazepines.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 238
- Patient must have been <11 years of age at the onset of LGS.
- Patient must have LGS.
- Patient must be on at least 1 AED.
- Parent or caregiver must be able to keep an accurate seizure diary.
- Etiology of patient's seizures is a progressive neurologic disease. Patients with tuberous sclerosis will not be excluded from study participation, unless there is a progressive tumor.
- Patient has had an episode of status epilepticus within 12 weeks of baseline.
- Patient has had an anoxic episode requiring resuscitation within 6 months of screening.
- Patient has a clinically significant history of an allergic reaction or significant sensitivity to benzodiazepines.
- Patient is taking more than 3 concurrent AEDs.
- Patient has been on the ketogenic diet for less than 30 days prior to screening or suffers from frequent stooling.
- If the patient has a Vagal Nerve Stimulator (VNS), the settings have not been stable for at least 30 days prior to screening.
- Patient has taken corticotropins in the 6 months prior to screening.
- Patient is currently taking long-term systemic steroids (excluding inhaled mediation for asthma treatment) or any other daily medication known to exacerbate epilepsy. An exception will be made of prophylactic medication, for example, for idiopathic nephrotic syndrome or asthma.
- If the patient is taking felbamate, has been taking it for less than 1 year prior to screening.
Other protocol-defined inclusion and exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Clobazam Low Dose Clobazam Low Dose - Clobazam Medium Dose Clobazam Medium Dose - Placebo Placebo - Clobazam High Dose Clobazam High Dose -
- Primary Outcome Measures
Name Time Method Percent Reduction in Number of Drop Seizures (12-week Maintenance Period). 4-week baseline period and 12-week maintenance period Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
- Secondary Outcome Measures
Name Time Method Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period). 4-week baseline period and the first 4 weeks of the 12-week maintenance period Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period). 4-week baseline period and the middle 4 weeks of the 12-week maintenance period Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period). 4-week baseline period and the last 4 weeks of the 12-week maintenance period Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). 4-week baseline period and the 12-week maintenance period Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (First 4 Weeks of the 12-week Maintenance Period). 4-week baseline period and the first 4 weeks of the 12-week maintenance period Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period). 4-week baseline period and the middle 4 weeks of the 12-week maintenance period Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period). 4-week baseline period and the last 4 weeks of the 12-week maintenance period Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Tolerance 4-week baseline period and first 4/first 8 weeks of the maintenance period Study responders who have ≥50% reduction in their drop seizure rate during the first 4 or first 8 weeks of maintenance compared to the 4 week baseline period.
Investigator Global Evaluations of the Patient's Overall Change in Symptoms. Week 15 The physician was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse".
Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. Week 15 The parent/caregiver was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse".
Trial Locations
- Locations (53)
University of Alabama at Birmingham
🇺🇸Huntsville, Alabama, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
The Children's Hospital
🇺🇸Aurora, Colorado, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Pediatric Neurology and Epilepsy Center
🇺🇸Loxahatchee, Florida, United States
Child Neurology Center of NW FL
🇺🇸Pensacola, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Pediatric Epilepsy & Neurology Specialists
🇺🇸Tampa, Florida, United States
Scroll for more (43 remaining)University of Alabama at Birmingham🇺🇸Huntsville, Alabama, United States