Clobazam in Patients With Lennox-Gastaut Syndrome

Epilepsy Clinical Trial

Official title:

Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00518713
• Other study ID #: 13110A
• Secondary ID: OV1012
• Status: Completed
• Phase: Phase 3
• First received: August 20, 2007
• Last updated: January 6, 2012
• Start date: August 2007
• Est. completion date: April 2010

Study information

• Verified date: January 2012
• Source: Lundbeck LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationBelarus: Ministry of HealthIndia: Drugs Controller General of IndiaLithuania: State Medicine Control Agency - Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: April 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsy
• Epilepsy, Generalized
• Seizures

Intervention

Drug:
• Clobazam Low Dose
0.25 mg/kg/day; tablets; orally; for 15-18 weeks
• Clobazam Medium Dose
0.5 mg/kg/day; tablets; orally; for 15-18 weeks
• Clobazam High Dose
1.0 mg/kg/day; tablets; orally; for 15-18 weeks
• Placebo
tablets; orally; daily for 15-18 weeks

Locations

Country	Name	City	State
Australia	Strategic Health Evaluators	Chatswood	New South Wales
Australia	Austin & Repatriation Hospital (Austin Health) Epilepsy Research Centre	Melbourne	Victoria
Australia	Royal Melbourne Hospital Department of Neurology	Melbourne	Victoria
Belarus	Vitebsk Regional Diagnostic Center	Vitebsk
India	Neurology Center	Ahmedabad	Gujarat
India	St. John's Medical College Hospital	Bangalore	Karnataka
India	Dr. Kamakshi Memorial Hospital	Chennai	Tamilnadu
India	Institute of Human Behaviour and Allied Sciences	Delhi	New Delhi
India	Deenanath Mangeshkar Hospital and Research Center	Erandawane	Pune
India	Apollo Gleneagles Hospitals	Kolkata	West Bengal
India	Chhatrapati Sahu Ji Maharaj Medical University	Lucknow	Uttra Pradesh
India	Christian Medical College	Ludhiana	Punjab
India	K. S. Hedge Medical Academy	Mangalore	Karnataka
India	Malikatta Neuro Center	Mangalore	Karnataka
India	Jaslok Hospital & Research Centre	Mumbai	Maharashtra
India	P.D. Hinduja National Hospital Medical Research Centre	Mumbai
India	Maulana Azad Medical College and Associated Lok Nayak Govind Ballabh Pant Hospitals and Guru Nanak Eye centre	New Delhi	Delhi
India	KEM Hospital & Research Centre	Pune	Maharashtra
Lithuania	Kaunas University of Medicine Hospital	Kaunas
United States	Medical College of Georgia	Augusta	Georgia
United States	The Children's Hospital	Aurora	Colorado
United States	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland
United States	Pediatric Neurology of Idaho Children's Specialty Center	Boise	Idaho
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Comprehensive Epilepsy Care Center for Children and Adults	Chesterfield	Missouri
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University Neurology, Inc.	Cincinnati	Ohio
United States	Children's Medical Center at UT Southwestern-Dallas	Dallas	Texas
United States	Cook Children's Health Care System	Fort Worth	Texas
United States	Baylor College of Medicine Pediatric Neurology	Houston	Texas
United States	University of Alabama at Birmingham	Huntsville	Alabama
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky, Kentucky Clinic, Department of Neurology	Lexington	Kentucky
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Pediatric Neurology and Epilepsy Center	Loxahatchee	Florida
United States	UTMG Pediatric Neurology	Memphis	Tennessee
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	St. Joseph's Regional Medical Center	Paterson	New Jersey
United States	Child Neurology Center of NW FL	Pensacola	Florida
United States	Jefferson Epilepsy Center	Philadelphia	Pennsylvania
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	LSU Health Sciences Center	Shreveport	Louisiana
United States	Minnesota Epilepsy Group	St. Paul	Minnesota
United States	Pediatric Epilepsy & Neurology Specialists	Tampa	Florida
United States	University of South Florida	Tampa	Florida
United States	Clinical Research Center of New Jersey (CRCNJ)	Voorhees	New Jersey
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Lundbeck LLC

Countries where clinical trial is conducted

United States,  Australia,  Belarus,  India,  Lithuania, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Reduction in Number of Drop Seizures (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.	4-week baseline period and 12-week maintenance period	No
Secondary	Percent Reduction in Number of Drop Seizures (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.	4-week baseline period and the first 4 weeks of the 12-week maintenance period	No
Secondary	Percent Reduction in Number of Drop Seizures (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.	4-week baseline period and the middle 4 weeks of the 12-week maintenance period	No
Secondary	Percent Reduction in Number of Drop Seizures (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.	4-week baseline period and the last 4 weeks of the 12-week maintenance period	No
Secondary	Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (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.	4-week baseline period and the 12-week maintenance period	No
Secondary	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).	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 first 4 weeks of the 12-week maintenance period	No
Secondary	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).	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 middle 4 weeks of the 12-week maintenance period	No
Secondary	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).	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 last 4 weeks of the 12-week maintenance period	No
Secondary	Tolerance	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.	4-week baseline period and first 4/first 8 weeks of the maintenance period	Yes
Secondary	Investigator Global Evaluations of the Patient's Overall Change in Symptoms.	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".	Week 15	No
Secondary	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 15	No