Clobazam in Subjects With Lennox-Gastaut Syndrome

Safety and Efficacy of Clobazam in Subjects With Lennox-Gastaut Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Epilepsy, Generalized; Seizures
• Intervention / Treatment: Drug: Clobazam Low Dose; Drug: Clobazam High 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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Tampa, Florida, United States, 33609
      • Pediatric Epilepsy & Neurology Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Childrens Hospital Boston
  • Minnesota
    • St. Paul, Minnesota, United States, 55102
      • Minnesota Epilepsy Group, P.A.
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Children's Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • University of Tennessee Health Science Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Pediatric Neurology Associates
    • Plano, Texas, United States, 75075
      • Texas Child Neurology, LLP
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Monarch Medical Research
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 28 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clobazam Low Dose	Drug: Clobazam Low Dose; 5 to 10 mg/day with doses in the morning and at bedtime; orally; Other Names: Onfi™
Experimental: Clobazam High Dose	Drug: Clobazam High Dose; 5 to 40 mg/day with doses in the morning and at bedtime; orally; Other Names: Onfi™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Reduction in Number of Drop Seizures.	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 4-week maintenance period
A Comparison of the High Dose Group to Low Dose Group of the Percent Reduction in Number of Drop Seizures.	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 4-week maintenance period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Patients Considered Treatment Responders Defined as Those With a >= 25%, >= 50%, >= 75%, and 100% Reduction in Drop Seizures.	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 4-week maintenance period
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 3
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 7

Collaborators and Investigators

• Sponsor: Lundbeck LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 13, 2005

Study Record Updates

• Last Update Posted (Estimate): February 9, 2012
• Last Update Submitted That Met QC Criteria: January 6, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Neurologic Manifestations; Genetic Diseases, Inborn; Epilepsy; Seizures; Epilepsy, Generalized; Lennox Gastaut Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; GABA Agents; Anticonvulsants; GABA-A Receptor Agonists; GABA Agonists; Clobazam
• Other Study ID Numbers: 13108A; OV1002 (Other Identifier: Former study ID)