Clobazam in Subjects With Lennox-Gastaut Syndrome

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety and Efficacy of Clobazam in Subjects With Lennox-Gastaut Syndrome

Conditions
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Epilepsy, Epilepsy, Generalized, Seizures

Intervention / Treatment
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* Drug: Clobazam Low Dose
* Drug: Clobazam High Dose


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject must have been <11 years of age at the onset of LGS Subject must have LGS Subject must be on at least 1 stable dose AED Parent or caregiver must be able to keep an accurate seizure diary 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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clobazam Low Dose<br> | Drug: Clobazam Low Dose<br>* 5 to 10 mg/day with doses in the morning and at bedtime; orally<br>* Other names: Onfi™;|
| Experimental: Clobazam High Dose<br> | Drug: Clobazam High Dose<br>* 5 to 40 mg/day with doses in the morning and at bedtime; orally<br>* Other names: Onfi™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Reduction in Number of Drop Seizures. | 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. | 4-week baseline period and 4-week maintenance period | 
| A Comparison of the High Dose Group to Low Dose Group of the Percent Reduction in Number of Drop Seizures. | 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. | 4-week baseline period and the 4-week maintenance period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients Considered Treatment Responders Defined as Those With a >= 25%, >= 50%, >= 75%, and 100% Reduction in Drop Seizures. | 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. | 4-week baseline period and 4-week maintenance period | 
| Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | 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. | Week 3 | 
| Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | 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. | Week 7 |