Clobazam in Subjects With Lennox-Gastaut Syndrome

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00162981
• Other study ID #: 13108A
• Secondary ID: OV1002
• Status: Completed
• Phase: Phase 2
• First received: September 9, 2005
• Last updated: January 6, 2012
• Start date: October 2005
• Est. completion date: October 2006

Study information

• Verified date: January 2012
• Source: Lundbeck LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: October 2006
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 30 Years

Eligibility

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 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
5 to 10 mg/day with doses in the morning and at bedtime; orally
• Clobazam High Dose
5 to 40 mg/day with doses in the morning and at bedtime; orally

Locations

Country	Name	City	State
United States	Childrens Hospital Boston	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Children's Hospital	Columbus	Ohio
United States	Dallas Pediatric Neurology Associates	Dallas	Texas
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Monarch Medical Research	Norfolk	Virginia
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Texas Child Neurology, LLP	Plano	Texas
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Minnesota Epilepsy Group, P.A.	St. Paul	Minnesota
United States	Pediatric Epilepsy & Neurology Specialists	Tampa	Florida
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Lundbeck LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	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 3	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 7	No