Clinical Trial: Clobazam in Patients With Lennox-Gastaut Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 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.

Detailed Summary:

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.


Sponsor: Lundbeck LLC

Current Primary Outcome: 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.


Original Primary Outcome: Percent reduction in number of drop seizures from the baseline period compared to the maintenance period.

Current Secondary Outcome:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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".
  • 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".


Original Secondary Outcome:

  • Percent of patients considered treatment responders defined as those with a >/=25%, >/= 50%, >/= 75% and 100% reduction in drop seizures from the baseline period compared to the maintenance period.
  • Global evaluations of the patient's overall change in symptoms.
  • Tolerance will be assessed in a subgroup of study responders in reduction of drop seizures during the maintenance period compared to baseline.


Information By: Lundbeck LLC

Dates:
Date Received: August 20, 2007
Date Started: August 2007
Date Completion:
Last Updated: January 6, 2012
Last Verified: January 2012