Clobazam in Patients With Lennox-Gastaut Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lundbeck LLC
ClinicalTrials.gov Identifier:
NCT00518713
First received: August 20, 2007
Last updated: January 6, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Epilepsy
Epilepsy, Generalized
Seizures
Drug: Clobazam Low Dose
Drug: Clobazam Medium Dose
Drug: Clobazam High Dose
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome

Resource links provided by NLM:


Further study details as provided by Lundbeck LLC:

Primary Outcome Measures:
  • Percent Reduction in Number of Drop Seizures (12-week Maintenance Period). [ Time Frame: 4-week baseline period and 12-week maintenance period ] [ Designated as safety issue: No ]
    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:
  • Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period). [ Time Frame: 4-week baseline period and the first 4 weeks of the 12-week maintenance period ] [ Designated as safety issue: No ]
    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.

  • Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period). [ Time Frame: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period ] [ Designated as safety issue: No ]
    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.

  • Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period). [ Time Frame: 4-week baseline period and the last 4 weeks of the 12-week maintenance period ] [ Designated as safety issue: No ]
    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.

  • Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). [ Time Frame: 4-week baseline period and the 12-week maintenance period ] [ Designated as safety issue: No ]
    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.

  • 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). [ Time Frame: 4-week baseline period and the first 4 weeks of the 12-week maintenance period ] [ Designated as safety issue: No ]
    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.

  • 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). [ Time Frame: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period ] [ Designated as safety issue: No ]
    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.

  • 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). [ Time Frame: 4-week baseline period and the last 4 weeks of the 12-week maintenance period ] [ Designated as safety issue: No ]
    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.

  • Tolerance [ Time Frame: 4-week baseline period and first 4/first 8 weeks of the maintenance period ] [ Designated as safety issue: Yes ]
    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.

  • Investigator Global Evaluations of the Patient's Overall Change in Symptoms. [ Time Frame: Week 15 ] [ Designated as safety issue: No ]
    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".

  • Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. [ Time Frame: Week 15 ] [ Designated as safety issue: No ]
    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".


Enrollment: 238
Study Start Date: August 2007
Study Completion Date: April 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clobazam Low Dose Drug: Clobazam Low Dose
0.25 mg/kg/day; tablets; orally; for 15-18 weeks
Other Name: Onfi™
Experimental: Clobazam Medium Dose Drug: Clobazam Medium Dose
0.5 mg/kg/day; tablets; orally; for 15-18 weeks
Other Name: Onfi™
Experimental: Clobazam High Dose Drug: Clobazam High Dose
1.0 mg/kg/day; tablets; orally; for 15-18 weeks
Other Name: Onfi™
Placebo Comparator: Placebo Drug: Placebo
tablets; orally; daily for 15-18 weeks

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

Ages Eligible for Study:   2 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00518713

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Huntsville, Alabama, United States, 35081
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85216
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
The Children's Hospital
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Pediatric Neurology and Epilepsy Center
Loxahatchee, Florida, United States, 33470
Child Neurology Center of NW FL
Pensacola, Florida, United States, 32504
University of South Florida
Tampa, Florida, United States, 33606
Pediatric Epilepsy & Neurology Specialists
Tampa, Florida, United States, 33609
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Idaho
Pediatric Neurology of Idaho Children's Specialty Center
Boise, Idaho, United States, 83712
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Children's Memorial Hospital
Chicago, Illinois, United States, 61516
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Kentucky
University of Kentucky, Kentucky Clinic, Department of Neurology
Lexington, Kentucky, United States, 40536-0284
United States, Louisiana
LSU Health Sciences Center
Shreveport, Louisiana, United States, 71103
United States, Maryland
Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland, United States, 20817
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
Minnesota Epilepsy Group
St. Paul, Minnesota, United States, 55012
United States, Missouri
The Comprehensive Epilepsy Care Center for Children and Adults
Chesterfield, Missouri, United States, 63017
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08901
St. Joseph's Regional Medical Center
Paterson, New Jersey, United States, 07503
Clinical Research Center of New Jersey (CRCNJ)
Voorhees, New Jersey, United States, 08043
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14450
United States, Ohio
University Neurology, Inc.
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
Jefferson Epilepsy Center
Philadelphia, Pennsylvania, United States, 19107
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
UTMG Pediatric Neurology
Memphis, Tennessee, United States, 38105
United States, Texas
Children's Medical Center at UT Southwestern-Dallas
Dallas, Texas, United States, 75235
Cook Children's Health Care System
Fort Worth, Texas, United States, 76104
Baylor College of Medicine Pediatric Neurology
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0211
Australia, New South Wales
Strategic Health Evaluators
Chatswood, New South Wales, Australia, 2067
Australia, Victoria
Austin & Repatriation Hospital (Austin Health) Epilepsy Research Centre
Melbourne, Victoria, Australia, 3081
Royal Melbourne Hospital Department of Neurology
Melbourne, Victoria, Australia, 3050
Belarus
Vitebsk Regional Diagnostic Center
Vitebsk, Belarus, 210023
India
Maulana Azad Medical College and Associated Lok Nayak Govind Ballabh Pant Hospitals and Guru Nanak Eye centre
New Delhi, Delhi, India, 110002
Neurology Center
Ahmedabad, Gujarat, India, 380006
St. John's Medical College Hospital
Bangalore, Karnataka, India, 560034
K. S. Hedge Medical Academy
Mangalore, Karnataka, India, 575018
Malikatta Neuro Center
Mangalore, Karnataka, India, 575002
Jaslok Hospital & Research Centre
Mumbai, Maharashtra, India, 400026
KEM Hospital & Research Centre
Pune, Maharashtra, India, 411 011
Institute of Human Behaviour and Allied Sciences
Delhi, New Delhi, India, 110095
Deenanath Mangeshkar Hospital and Research Center
Erandawane, Pune, India, 411004
Christian Medical College
Ludhiana, Punjab, India, 1410108
Dr. Kamakshi Memorial Hospital
Chennai, Tamilnadu, India, 600 100
Chhatrapati Sahu Ji Maharaj Medical University
Lucknow, Uttra Pradesh, India, 226 003
Apollo Gleneagles Hospitals
Kolkata, West Bengal, India, 700054
P.D. Hinduja National Hospital Medical Research Centre
Mumbai, India, 400016
Lithuania
Kaunas University of Medicine Hospital
Kaunas, Lithuania, LT 50009
Sponsors and Collaborators
Lundbeck LLC
Investigators
Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@lundbeck.com
  More Information

Publications:
Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA, on behalf of the OV-1012 Study Investigators. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology 77(15): 1473-1481, 2011.

Responsible Party: Lundbeck LLC
ClinicalTrials.gov Identifier: NCT00518713     History of Changes
Other Study ID Numbers: 13110A, OV1012
Study First Received: August 20, 2007
Results First Received: November 7, 2011
Last Updated: January 6, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Belarus: Ministry of Health
India: Drugs Controller General of India
Lithuania: State Medicine Control Agency - Ministry of Health
United States: Food and Drug Administration

Keywords provided by Lundbeck LLC:
Epilepsy
Lennox-Gastaut Syndrome
Drop seizures
Clobazam

Additional relevant MeSH terms:
Epilepsy
Epilepsy, Generalized
Intellectual Disability
Seizures
Spasms, Infantile
Syndrome
Brain Diseases
Central Nervous System Diseases
Disease
Mental Disorders
Mental Disorders Diagnosed in Childhood
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Clobazam
Anticonvulsants
Central Nervous System Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014