Clobazam in Subjects With Lennox-Gastaut Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lundbeck LLC
ClinicalTrials.gov Identifier:
NCT00162981
First received: September 9, 2005
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 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.


Condition Intervention Phase
Epilepsy
Epilepsy, Generalized
Seizures
Drug: Clobazam Low Dose
Drug: Clobazam High Dose
Phase 2

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: Safety and Efficacy of Clobazam in Subjects 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. [ Time Frame: 4-week baseline period and 4-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.

  • A Comparison of the High Dose Group to Low Dose Group of the Percent Reduction in Number of Drop Seizures. [ Time Frame: 4-week baseline period and the 4-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 of Patients Considered Treatment Responders Defined as Those With a >= 25%, >= 50%, >= 75%, and 100% Reduction in Drop Seizures. [ Time Frame: 4-week baseline period and 4-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.

  • Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. [ Time Frame: Week 3 ] [ 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".

  • Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. [ Time Frame: Week 7 ] [ 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: 68
Study Start Date: October 2005
Study Completion Date: October 2006
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clobazam Low Dose Drug: Clobazam Low Dose
5 to 10 mg/day with doses in the morning and at bedtime; orally
Other Name: Onfi™
Experimental: Clobazam High Dose Drug: Clobazam High Dose
5 to 40 mg/day with doses in the morning and at bedtime; orally
Other Name: Onfi™

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

Ages Eligible for Study:   2 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00162981

Locations
United States, Arizona
Barrow Neurological Institute
Phoenix, Arizona, United States, 85013
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Pediatric Epilepsy & Neurology Specialists
Tampa, Florida, United States, 33609
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Childrens Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Minnesota
Minnesota Epilepsy Group, P.A.
St. Paul, Minnesota, United States, 55102
United States, Ohio
Children's Hospital
Columbus, Ohio, United States, 43205
United States, Tennessee
University of Tennessee Health Science Center
Memphis, Tennessee, United States, 38105
United States, Texas
Dallas Pediatric Neurology Associates
Dallas, Texas, United States, 75230
Texas Child Neurology, LLP
Plano, Texas, United States, 75075
United States, Virginia
Monarch Medical Research
Norfolk, Virginia, United States, 23510
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53201
Sponsors and Collaborators
Lundbeck LLC
Investigators
Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@lundbeck.com
  More Information

Publications:
Responsible Party: Lundbeck LLC
ClinicalTrials.gov Identifier: NCT00162981     History of Changes
Other Study ID Numbers: 13108A, OV1002
Study First Received: September 9, 2005
Results First Received: November 7, 2011
Last Updated: January 6, 2012
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 18, 2014