Clobazam in Patients With Lennox-Gastaut Syndrome
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| ClinicalTrials.gov Identifier: NCT00518713 |
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Recruitment Status :
Completed
First Posted : August 21, 2007
Results First Posted : February 9, 2012
Last Update Posted : February 9, 2012
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Sponsor:
Lundbeck LLC
Information provided by (Responsible Party):
Lundbeck LLC
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Epilepsy Epilepsy, Generalized Seizures | Drug: Clobazam Low Dose Drug: Clobazam Medium Dose Drug: Clobazam High Dose Drug: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 238 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome |
| Study Start Date : | August 2007 |
| Actual Primary Completion Date : | December 2009 |
| Actual Study Completion Date : | April 2010 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lennox-Gastaut syndrome
Pyridoxal 5'-phosphate-dependent epilepsy
MedlinePlus related topics:
Seizures
Drug Information available for:
Clobazam
| Arm | Intervention/treatment |
|---|---|
| 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 |
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 ]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 ]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".
Other Outcome Measures:
- 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.
- 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.
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| Ages Eligible for Study: | 2 Years to 60 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00518713
Locations
Show 53 study locations
Sponsors and Collaborators
Lundbeck LLC
Investigators
| Study Director: | Email contact via H. Lundbeck A/S | LundbeckClinicalTrials@lundbeck.com |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Lundbeck LLC |
| ClinicalTrials.gov Identifier: | NCT00518713 |
| Other Study ID Numbers: |
13110A OV1012 ( Other Identifier: Former study ID ) |
| First Posted: | August 21, 2007 Key Record Dates |
| Results First Posted: | February 9, 2012 |
| Last Update Posted: | February 9, 2012 |
| Last Verified: | January 2012 |
Keywords provided by Lundbeck LLC:
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Epilepsy Lennox-Gastaut Syndrome Drop seizures Clobazam |
Additional relevant MeSH terms:
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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 |