Clobazam in Subjects With Lennox-Gastaut Syndrome

• ClinicalTrials.gov Identifier: NCT00162981
• Recruitment Status: Completed
• First Posted: September 13, 2005
• Results First Posted: February 9, 2012
• Last Update Posted: February 9, 2012
• Sponsor: Lundbeck LLC
• Information provided by (Responsible Party): Lundbeck LLC

Study Description

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 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 or disease	Intervention/treatment	Phase
Epilepsy; Epilepsy, Generalized; Seizures	Drug: Clobazam Low Dose; Drug: Clobazam High Dose	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Clobazam in Subjects With Lennox-Gastaut Syndrome
• Study Start Date: October 2005
• Actual Primary Completion Date: August 2006
• Actual Study Completion Date: October 2006

Arms and Interventions

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 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™

Outcome Measures

Primary Outcome Measures :

1. Percent Reduction in Number of Drop Seizures. [ Time Frame: 4-week baseline period and 4-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.
2. 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 ]
   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 :

1. 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 ]
   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.
2. Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. [ Time Frame: Week 3 ]
   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".
3. Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. [ Time Frame: Week 7 ]
   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".

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

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:

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.

• Responsible Party: Lundbeck LLC
• ClinicalTrials.gov Identifier: NCT00162981
• Other Study ID Numbers: 13108A; OV1002 ( Other Identifier: Former study ID )
• First Posted: September 13, 2005
• Results First Posted: February 9, 2012
• Last Update Posted: February 9, 2012
• Last Verified: January 2012

Additional relevant MeSH terms:

Epilepsy; Seizures; Lennox Gastaut Syndrome; Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epileptic Syndromes; Genetic Diseases, Inborn; Clobazam; Anticonvulsants; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs; GABA-A Receptor Agonists; GABA Agonists; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action