Clobazam in Patients With Lennox-Gastaut Syndrome - Full Text View

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:

Genetics Home Reference related topics: Lennox-Gastaut syndrome pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

Drug Information available for: Clobazam

U.S. FDA Resources

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

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

Show 53 Study Locations

Sponsors and Collaborators

Lundbeck LLC

Investigators

Study Director:

Email contact via H. Lundbeck A/S

LundbeckClinicalTrials@lundbeck.com

More Information

No publications provided

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:

Spasms, Infantile
Epilepsy
Epilepsy, Generalized
Seizures
Mental Retardation
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations

Signs and Symptoms
Neurobehavioral Manifestations
Mental Disorders Diagnosed in Childhood
Mental Disorders
Clobazam
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013