Clobazam in Subjects With Lennox-Gastaut Syndrome

Phase 2

Completed

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 subjects 2 to 30 years of age with Lennox-Gastaut Syndrome (LGS). Subjects will be enrolled at approximately 10 investigational sites in the U.S. for up to 15 weeks. Subjects will be randomly assigned to either a low dose or a high dose. The study will include a baseline period, a titration period and a maintenance period. After the maintenance period, subjects 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. While antiepileptic medications are the mainstay of treatment, no one antiepileptic drug (AED) provides satisfactory relief for all or most patients with LGS and a combination of treatments is often required. Many patients with LGS are refractory to standard AED treatment.

More effective and better tolerated treatment options are needed for this population of medically intractable epilepsy patients. Clobazam is unique in that it is the only non-1, 4-benzodiazepine used in the treatment of epilepsy.

Recruitment & Eligibility

Inclusion Criteria

Key

Exclusion Criteria

Etiology of subject's seizures is a progressive neurologic disease. Subjects with tuberous sclerosis will not be excluded from study participation
Subject has had an episode of status epilepticus within 12 weeks of baseline
Subject has had an anoxic episode requiring resuscitation within 1 year of screening
Subject has had a clinically significant history of an allergic reaction or significant sensitivity to benzodiazepines
Subject is taking more than 3 concurrent AEDs. Note: Vagal Nerve Stimulation (VNS) or ketogenic diet is allowed and each will be counted as one of the three allowed AEDs
If the subject is on the ketogenic diet, has been for less than 4 weeks prior to screening or suffers from frequent stooling
If the subject has a VNS, the settings have not been stable for at least 4 weeks prior to screening
Subject has taken corticotropins in the 6 months prior to screening
Subject is currently taking long-term systemic steroids (excluding inhaled medication for asthma treatment) or any other daily medication known to exacerbate epilepsy. An exception will be made of prophylactic medication, for example, for urinary tract infections or asthma
If the subject is taking felbamate, has been taking it for less than 1 year prior to screening or previous treatment with felbamate resulted in withdrawal due to liver or bone marrow adverse events

Arm && Interventions

Group	Intervention	Description
Clobazam Low Dose	Clobazam Low Dose	-
Clobazam High Dose	Clobazam High Dose	-

Primary Outcome Measures

Name	Time	Method
Percent Reduction in Number of Drop Seizures.	4-week baseline period and 4-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.
A Comparison of the High Dose Group to Low Dose Group of the Percent Reduction in Number of Drop Seizures.	4-week baseline period and the 4-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 of Patients Considered Treatment Responders Defined as Those With a >= 25%, >= 50%, >= 75%, and 100% Reduction in Drop Seizures.	4-week baseline period and 4-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.
Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.	Week 7	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".

Locations (14): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
University of Tennessee Health Science Center
🇺🇸
Memphis, Tennessee, United States
Dallas Pediatric Neurology Associates
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Dallas, Texas, United States
Children's Hospital of Wisconsin
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Milwaukee, Wisconsin, United States
Childrens Hospital Los Angeles
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Los Angeles, California, United States
Pediatric Epilepsy & Neurology Specialists
🇺🇸
Tampa, Florida, United States
Childrens Hospital Boston
🇺🇸
Boston, Massachusetts, United States
Children's Hospital
🇺🇸
Columbus, Ohio, United States
Monarch Medical Research
🇺🇸
Norfolk, Virginia, United States
Minnesota Epilepsy Group, P.A.
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St. Paul, Minnesota, United States
Texas Child Neurology, LLP
🇺🇸
Plano, Texas, United States
Barrow Neurological Institute
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Phoenix, Arizona, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States