Clinical trial NCT00162981: Clobazam in Subjects With Lennox-Gastaut Syndrome
Official title: Safety and Efficacy of Clobazam in Subjects With Lennox-Gastaut Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Epilepsy, Generalized
Seizures
Lead sponsor: Lundbeck LLC
Sponsor class: INDUSTRY
First posted: 2005-09-13
Enrollment: 68
Sex: ALL
Minimum age (years): 2
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Reduction in Number of Drop Seizures.
timeFrame: 4-week baseline period and 4-week maintenance period
measure: A Comparison of the High Dose Group to Low Dose Group of the Percent Reduction in Number of Drop Seizures.
timeFrame: 4-week baseline period and the 4-week maintenance period
Secondary outcomes:
measure: Percent of Patients Considered Treatment Responders Defined as Those With a >= 25%, >= 50%, >= 75%, and 100% Reduction in Drop Seizures.
timeFrame: 4-week baseline period and 4-week maintenance period
measure: Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.
timeFrame: Week 3
measure: Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.
timeFrame: Week 7
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: Pediatric Epilepsy & Neurology Specialists
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Childrens Hospital Boston
state: Massachusetts
city: St. Paul
country: United States
facility: Minnesota Epilepsy Group, P.A.
state: Minnesota
city: Columbus
country: United States
facility: Children's Hospital
state: Ohio
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Dallas
country: United States
facility: Dallas Pediatric Neurology Associates
state: Texas
city: Plano
country: United States
facility: Texas Child Neurology, LLP
state: Texas
city: Norfolk
country: United States
facility: Monarch Medical Research
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: Conry JA, Ng YT, Paolicchi JM, Kernitsky L, Mitchell WG, Ritter FJ, Collins SD, Tracy K, Kormany WN, Abdulnabi R, Riley B, Stolle J. Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia. 2009 May;50(5):1158-66. doi: 10.1111/j.1528-1167.2008.01935.x. Epub 2008 Dec 15.