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NCT Number: NCT00518713

Clobazam in Patients 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 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.

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Key information

Conditions

Epilepsy Brain Diseases Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Consciousness Disorders Epilepsy, Generalized Epileptic Syndromes Genetic Diseases, Inborn Lennox Gastaut Syndrome Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Pathological Conditions, Signs and Symptoms Seizures Signs and Symptoms Syncope Unconsciousness

Age range

2 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Strategic Health Evaluators, Chatswood, New South Wales, Australia

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Clobazam Low Dose

Drug

0.25 mg/kg/day; tablets; orally; for 15-18 weeks

Other names: Onfi™

Clobazam Medium Dose

Drug

0.5 mg/kg/day; tablets; orally; for 15-18 weeks

Other names: Onfi™

Clobazam High Dose

Drug

1.0 mg/kg/day; tablets; orally; for 15-18 weeks

Other names: Onfi™

Placebo

Drug

tablets; orally; daily for 15-18 weeks

Primary outcomes

  1. Percent Reduction in Number of Drop Seizures (12-week Maintenance Period).

    Time frame: 4-week baseline period and 12-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 outcomes

  1. 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

    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. 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

    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.

  3. 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

    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. 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

    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.

  5. 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

    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.

  6. 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

    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.

  7. 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

    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.

  8. Tolerance

    Time frame: 4-week baseline period and first 4/first 8 weeks of the maintenance period

    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.

  9. Investigator Global Evaluations of the Patient's Overall Change in Symptoms.

    Time frame: Week 15

    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".

  10. Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.

    Time frame: Week 15

    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".

Other outcomes

  1. Percent Reduction in the Number of Non-drop Seizures.

    Time frame: 4-week baseline period and the 12-week maintenance period

    This outcome measure evaluated the percent reduction (average per week) in non-drop Seizures. Non-drop seizures were other seizures not meeting the drop seizure definition. Drop seizures were defined as a drop attack or spell (atonic, tonic or myoclonic) involving the entire body, trunk, or head that led to a fall, injury, slumping in chair, or head hitting surface or that could have led to a fall or injury, depending on the position of the patient at the time of the attack or spell.

  2. Percent Reduction of Total (Drop and Non-Drop) Seizures.

    Time frame: 4-week baseline period and 12-week maintenance period

    This outcome measure evaluated the percent reduction in average weekly rate in total (drop and non-drop) seizures. Drop seizures were defined as a drop attack or spell (atonic, tonic or myoclonic) involving the entire body, trunk, or head that led to a fall, injury, slumping in chair, or head hitting surface or that could have led to a fall or injury, depending on the position of the patient at the time of the attack or spell. Non-drop seizures were other seizures not meeting the drop seizure definition.

Sponsors and collaborators

Lead sponsor

Lundbeck LLC

Industry

Registry information

Official study title

Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome

Important dates

Study start
2007
Primary completion
2009
Study completion
2010
First posted
Aug 21, 2007
Registry last updated
Feb 9, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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