Clinical trial NCT00518713: Clobazam in Patients With Lennox-Gastaut Syndrome
Official title: Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Epilepsy, Generalized
Seizures
Keywords: Epilepsy
Lennox-Gastaut Syndrome
Drop seizures
Clobazam
Lead sponsor: Lundbeck LLC
Sponsor class: INDUSTRY
First posted: 2007-08-21
Enrollment: 238
Sex: ALL
Minimum age (years): 2
Maximum age (years): 60
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 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percent Reduction in Number of Drop Seizures (12-week Maintenance Period).
timeFrame: 4-week baseline period and 12-week maintenance period
Secondary outcomes:
measure: Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).
timeFrame: 4-week baseline period and the first 4 weeks of the 12-week maintenance period
measure: Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).
timeFrame: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period
measure: Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).
timeFrame: 4-week baseline period and the last 4 weeks of the 12-week maintenance period
measure: Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period).
timeFrame: 4-week baseline period and the 12-week maintenance period
measure: 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).
timeFrame: 4-week baseline period and the first 4 weeks of the 12-week maintenance period
measure: 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).
timeFrame: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period
measure: 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).
timeFrame: 4-week baseline period and the last 4 weeks of the 12-week maintenance period
measure: Tolerance
timeFrame: 4-week baseline period and first 4/first 8 weeks of the maintenance period
measure: Investigator Global Evaluations of the Patient's Overall Change in Symptoms.
timeFrame: Week 15
measure: Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.
timeFrame: Week 15
Other outcomes:
measure: Percent Reduction in the Number of Non-drop Seizures.
timeFrame: 4-week baseline period and the 12-week maintenance period
measure: Percent Reduction of Total (Drop and Non-Drop) Seizures.
timeFrame: 4-week baseline period and 12-week maintenance period
Locations:
city: Huntsville
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Loxahatchee
country: United States
facility: Pediatric Neurology and Epilepsy Center
state: Florida
city: Pensacola
country: United States
facility: Child Neurology Center of NW FL
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: Pediatric Epilepsy & Neurology Specialists
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Boise
country: United States
facility: Pediatric Neurology of Idaho Children's Specialty Center
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky, Kentucky Clinic, Department of Neurology
state: Kentucky
city: Shreveport
country: United States
facility: LSU Health Sciences Center
state: Louisiana
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: St. Paul
country: United States
facility: Minnesota Epilepsy Group
state: Minnesota
city: Chesterfield
country: United States
facility: The Comprehensive Epilepsy Care Center for Children and Adults
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Regional Medical Center
state: New Jersey
city: Voorhees
country: United States
facility: Clinical Research Center of New Jersey (CRCNJ)
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: University Neurology, Inc.
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Epilepsy Center
state: Pennsylvania
city: Memphis
country: United States
facility: UTMG Pediatric Neurology
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center at UT Southwestern-Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Health Care System
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Pediatric Neurology
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Chatswood
country: Australia
facility: Strategic Health Evaluators
state: New South Wales
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital Department of Neurology
state: Victoria
city: Melbourne
country: Australia
facility: Austin & Repatriation Hospital (Austin Health) Epilepsy Research Centre
state: Victoria
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Diagnostic Center
city: New Delhi
country: India
facility: Maulana Azad Medical College and Associated Lok Nayak Govind Ballabh Pant Hospitals and Guru Nanak Eye centre
state: Delhi
city: Ahmedabad
country: India
facility: Neurology Center
state: Gujarat
city: Bangalore
country: India
facility: St. John's Medical College Hospital
state: Karnataka
city: Mangalore
country: India
facility: Malikatta Neuro Center
state: Karnataka
city: Mangalore
country: India
facility: K. S. Hedge Medical Academy
state: Karnataka
city: Mumbai
country: India
facility: Jaslok Hospital & Research Centre
state: Maharashtra
city: Pune
country: India
facility: KEM Hospital & Research Centre
state: Maharashtra
city: Delhi
country: India
facility: Institute of Human Behaviour and Allied Sciences
state: New Delhi
city: Erandawane
country: India
facility: Deenanath Mangeshkar Hospital and Research Center
state: Pune
city: Ludhiana
country: India
facility: Christian Medical College
state: Punjab
city: Chennai
country: India
facility: Dr. Kamakshi Memorial Hospital
state: Tamilnadu
city: Lucknow
country: India
facility: Chhatrapati Sahu Ji Maharaj Medical University
state: Uttra Pradesh
city: Kolkata
country: India
facility: Apollo Gleneagles Hospitals
state: West Bengal
city: Mumbai
country: India
facility: P.D. Hinduja National Hospital Medical Research Centre
city: Kaunas
country: Lithuania
facility: Kaunas University of Medicine Hospital
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology. 2011 Oct 11;77(15):1473-81. doi: 10.1212/WNL.0b013e318232de76. Epub 2011 Sep 28.
citation: 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.
citation: Gidal BE, Wechsler RT, Sankar R, Montouris GD, White HS, Cloyd JC, Kane MC, Peng G, Tworek DM, Shen V, Isojarvi J. Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study. Neurology. 2016 Oct 25;87(17):1806-1812. doi: 10.1212/WNL.0000000000003253. Epub 2016 Sep 28.