Epilepsy, Epilepsy, Generalized, Seizures
Conditions
Keywords
Epilepsy, Lennox-Gastaut Syndrome, Drop seizures, Clobazam
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 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.
Interventions
0.25 mg/kg/day; tablets; orally; for 15-18 weeks
DRUGClobazam Medium Dose
0.5 mg/kg/day; tablets; orally; for 15-18 weeks
1.0 mg/kg/day; tablets; orally; for 15-18 weeks
DRUGPlacebo
tablets; orally; daily for 15-18 weeks
Sponsors
Lundbeck LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in Number of Drop Seizures (12-week Maintenance Period). | 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
| Measure | Time frame | Description |
|---|---|---|
| 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). | 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 (First 4 Weeks of the 12-week Maintenance Period). | 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). | 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). | 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). | 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. |
| Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | 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. | 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. |
| 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). | 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 (Last 4 Weeks of the 12-week Maintenance Period). | 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in the Number of Non-drop Seizures. | 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. | 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. |
Countries
Australia, Belarus, India, Lithuania, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clobazam Low Dose 0.25 mg/kg/day; tablets; orally; for 15-18 weeks | 58 |
| Clobazam Medium Dose 0.5 mg/kg/day; tablets; orally; for 15-18 weeks | 62 |
| Clobazam High Dose 1.0 mg/kg/day; tablets; orally; for 15-18 weeks | 59 |
| Placebo tablets; orally; daily for 15-18 weeks | 59 |
| Total | 238 |
Baseline characteristics
| Characteristic | Clobazam Low Dose | Clobazam Medium Dose | Clobazam High Dose | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 48 Participants | 48 Participants | 49 Participants | 48 Participants | 193 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 14 Participants | 10 Participants | 11 Participants | 45 Participants |
| Age Continuous | 10.9 years STANDARD_DEVIATION 7.24 | 14.1 years STANDARD_DEVIATION 10.42 | 11.7 years STANDARD_DEVIATION 8.48 | 13.0 years STANDARD_DEVIATION 9.17 | 12.4 years STANDARD_DEVIATION 8.96 |
| Sex: Female, Male Female | 22 Participants | 26 Participants | 25 Participants | 21 Participants | 94 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 34 Participants | 38 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 58 | 55 / 62 | 45 / 59 | 40 / 59 |
| serious Total, serious adverse events | 3 / 58 | 6 / 62 | 5 / 59 | 2 / 59 |
Outcome results
Primary
Percent Reduction in Number of Drop Seizures (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.
Time frame: 4-week baseline period and 12-week maintenance period
Population: Modified Intent-to-Treat (MITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Clobazam Low Dose | Percent Reduction in Number of Drop Seizures (12-week Maintenance Period). | 41.2 Percent Reduction |
| Clobazam Medium Dose | Percent Reduction in Number of Drop Seizures (12-week Maintenance Period). | 49.4 Percent Reduction |
| Clobazam High Dose | Percent Reduction in Number of Drop Seizures (12-week Maintenance Period). | 68.3 Percent Reduction |
| Placebo | Percent Reduction in Number of Drop Seizures (12-week Maintenance Period). | 12.1 Percent Reduction |
Comparison: Analysis of covariance (ANCOVA) with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.012ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0015ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: <0.0001ANCOVA
Secondary
Investigator Global Evaluations of the Patient's Overall Change in Symptoms.
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.
Time frame: Week 15
Population: Those patients in the MITT population who completed a Physician Global Evaluation at Week 15.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clobazam Low Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally worse | 2 participants |
| Clobazam Low Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Very much worse | 0 participants |
| Clobazam Low Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally improved | 13 participants |
| Clobazam Low Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Much improved | 20 participants |
| Clobazam Low Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Very much improved | 4 participants |
| Clobazam Low Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Much worse | 1 participants |
| Clobazam Low Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | No change | 12 participants |
| Clobazam Medium Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Much improved | 27 participants |
| Clobazam Medium Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Very much improved | 10 participants |
| Clobazam Medium Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally worse | 2 participants |
| Clobazam Medium Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Very much worse | 0 participants |
| Clobazam Medium Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | No change | 9 participants |
| Clobazam Medium Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Much worse | 0 participants |
| Clobazam Medium Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally improved | 9 participants |
| Clobazam High Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Much improved | 23 participants |
| Clobazam High Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Very much improved | 8 participants |
| Clobazam High Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally improved | 8 participants |
| Clobazam High Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | No change | 6 participants |
| Clobazam High Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally worse | 3 participants |
| Clobazam High Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Much worse | 1 participants |
| Clobazam High Dose | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Very much worse | 0 participants |
| Placebo | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Much improved | 10 participants |
| Placebo | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Very much worse | 0 participants |
| Placebo | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Much worse | 1 participants |
| Placebo | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Very much improved | 3 participants |
| Placebo | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | No change | 22 participants |
| Placebo | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally worse | 6 participants |
| Placebo | Investigator Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally improved | 13 participants |
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.
Time frame: Week 15
Population: Those patients in the MITT population who had a baseline and Week 15 parent/caregiver global evaluations were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clobazam Low Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Much worse | 0 participants |
| Clobazam Low Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally worse | 2 participants |
| Clobazam Low Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Very much worse | 1 participants |
| Clobazam Low Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Much improved | 14 participants |
| Clobazam Low Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Very much improved | 8 participants |
| Clobazam Low Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally improved | 20 participants |
| Clobazam Low Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | No change | 8 participants |
| Clobazam Medium Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally worse | 2 participants |
| Clobazam Medium Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally improved | 14 participants |
| Clobazam Medium Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Very much improved | 13 participants |
| Clobazam Medium Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Much worse | 2 participants |
| Clobazam Medium Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | No change | 7 participants |
| Clobazam Medium Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Very much worse | 0 participants |
| Clobazam Medium Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Much improved | 19 participants |
| Clobazam High Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | No change | 4 participants |
| Clobazam High Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Much improved | 18 participants |
| Clobazam High Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally worse | 3 participants |
| Clobazam High Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Very much improved | 11 participants |
| Clobazam High Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Much worse | 2 participants |
| Clobazam High Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally improved | 11 participants |
| Clobazam High Dose | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Very much worse | 0 participants |
| Placebo | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Very much worse | 0 participants |
| Placebo | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Very much improved | 4 participants |
| Placebo | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Much improved | 10 participants |
| Placebo | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally improved | 11 participants |
| Placebo | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Minimally worse | 6 participants |
| Placebo | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | Much worse | 3 participants |
| Placebo | Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms. | No change | 21 participants |
Secondary
Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (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.
Time frame: 4-week baseline period and the 12-week maintenance period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clobazam Low Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 25% reduction | 34 Percent of responders |
| Clobazam Low Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 50% reduction | 23 Percent of responders |
| Clobazam Low Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 75% reduction | 15 Percent of responders |
| Clobazam Low Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | 100% reduction | 4 Percent of responders |
| Clobazam Medium Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 50% reduction | 34 Percent of responders |
| Clobazam Medium Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 75% reduction | 22 Percent of responders |
| Clobazam Medium Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | 100% reduction | 7 Percent of responders |
| Clobazam Medium Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 25% reduction | 46 Percent of responders |
| Clobazam High Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 75% reduction | 31 Percent of responders |
| Clobazam High Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 50% reduction | 38 Percent of responders |
| Clobazam High Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | 100% reduction | 12 Percent of responders |
| Clobazam High Dose | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 25% reduction | 41 Percent of responders |
| Placebo | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | 100% reduction | 2 Percent of responders |
| Placebo | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 50% reduction | 18 Percent of responders |
| Placebo | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 25% reduction | 28 Percent of responders |
| Placebo | Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period). | ≥ 75% reduction | 6 Percent of responders |
Comparison: ≥ 25% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.1324ANCOVA
Comparison: ≥ 25% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0026ANCOVA
Comparison: ≥ 25% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0004ANCOVA
Comparison: ≥ 50% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.3383ANCOVA
Comparison: ≥ 50% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0159ANCOVA
Comparison: ≥ 50% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: <0.0001ANCOVA
Comparison: ≥ 75% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0279ANCOVA
Comparison: ≥ 75% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.001ANCOVA
Comparison: ≥ 75% reduction. ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: <0.0001ANCOVA
Secondary
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).
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.
Time frame: 4-week baseline period and the first 4 weeks of the 12-week maintenance period
Population: MITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clobazam Low Dose | 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). | ≥ 25% reduction | 71.7 Percent of responders |
| Clobazam Low Dose | 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). | ≥ 50% reduction | 47.2 Percent of responders |
| Clobazam Low Dose | 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). | ≥ 75% reduction | 35.8 Percent of responders |
| Clobazam Low Dose | 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). | 100% reduction | 13.2 Percent of responders |
| Clobazam Medium Dose | 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). | ≥ 50% reduction | 72.4 Percent of responders |
| Clobazam Medium Dose | 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). | ≥ 75% reduction | 44.8 Percent of responders |
| Clobazam Medium Dose | 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). | 100% reduction | 19.0 Percent of responders |
| Clobazam Medium Dose | 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). | ≥ 25% reduction | 82.8 Percent of responders |
| Clobazam High Dose | 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). | ≥ 75% reduction | 63.3 Percent of responders |
| Clobazam High Dose | 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). | ≥ 50% reduction | 77.6 Percent of responders |
| Clobazam High Dose | 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). | 100% reduction | 30.6 Percent of responders |
| Clobazam High Dose | 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). | ≥ 25% reduction | 89.8 Percent of responders |
| Placebo | 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). | 100% reduction | 3.5 Percent of responders |
| Placebo | 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). | ≥ 50% reduction | 31.6 Percent of responders |
| Placebo | 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). | ≥ 25% reduction | 52.6 Percent of responders |
| Placebo | 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). | ≥ 75% reduction | 14.0 Percent of responders |
Secondary
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).
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.
Time frame: 4-week baseline period and the last 4 weeks of the 12-week maintenance period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clobazam Low Dose | 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). | ≥ 25% reduction | 66.0 Percent Responders |
| Clobazam Low Dose | 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). | ≥ 50% reduction | 45.3 Percent Responders |
| Clobazam Low Dose | 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). | ≥ 75% reduction | 28.3 Percent Responders |
| Clobazam Low Dose | 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). | 100% reduction | 13.2 Percent Responders |
| Clobazam Medium Dose | 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). | ≥ 50% reduction | 50.0 Percent Responders |
| Clobazam Medium Dose | 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). | ≥ 75% reduction | 36.2 Percent Responders |
| Clobazam Medium Dose | 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). | 100% reduction | 15.5 Percent Responders |
| Clobazam Medium Dose | 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). | ≥ 25% reduction | 60.3 Percent Responders |
| Clobazam High Dose | 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). | ≥ 75% reduction | 57.1 Percent Responders |
| Clobazam High Dose | 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). | ≥ 50% reduction | 67.3 Percent Responders |
| Clobazam High Dose | 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). | 100% reduction | 20.4 Percent Responders |
| Clobazam High Dose | 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). | ≥ 25% reduction | 71.4 Percent Responders |
| Placebo | 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). | 100% reduction | 5.3 Percent Responders |
| Placebo | 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). | ≥ 50% reduction | 29.8 Percent Responders |
| Placebo | 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). | ≥ 25% reduction | 43.9 Percent Responders |
| Placebo | 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). | ≥ 75% reduction | 12.3 Percent Responders |
Secondary
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).
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.
Time frame: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clobazam Low Dose | 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). | ≥ 25% reduction | 64.2 Percent Responders |
| Clobazam Low Dose | 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). | ≥ 50% reduction | 43.4 Percent Responders |
| Clobazam Low Dose | 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). | ≥ 75% reduction | 28.3 Percent Responders |
| Clobazam Low Dose | 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). | 100% reduction | 9.4 Percent Responders |
| Clobazam Medium Dose | 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). | ≥ 50% reduction | 51.7 Percent Responders |
| Clobazam Medium Dose | 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). | ≥ 75% reduction | 34.5 Percent Responders |
| Clobazam Medium Dose | 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). | 100% reduction | 15.5 Percent Responders |
| Clobazam Medium Dose | 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). | ≥ 25% reduction | 65.5 Percent Responders |
| Clobazam High Dose | 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). | ≥ 75% reduction | 59.2 Percent Responders |
| Clobazam High Dose | 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). | ≥ 50% reduction | 71.4 Percent Responders |
| Clobazam High Dose | 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). | 100% reduction | 26.5 Percent Responders |
| Clobazam High Dose | 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). | ≥ 25% reduction | 75.5 Percent Responders |
| Placebo | 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). | 100% reduction | 5.3 Percent Responders |
| Placebo | 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). | ≥ 50% reduction | 24.6 Percent Responders |
| Placebo | 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). | ≥ 25% reduction | 50.9 Percent Responders |
| Placebo | 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). | ≥ 75% reduction | 12.3 Percent Responders |
Secondary
Percent Reduction in Number of Drop Seizures (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.
Time frame: 4-week baseline period and the first 4 weeks of the 12-week maintenance period
Population: MITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Clobazam Low Dose | Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period). | 47.8 Percent reduction |
| Clobazam Medium Dose | Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period). | 58.9 Percent reduction |
| Clobazam High Dose | Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period). | 71.0 Percent reduction |
| Placebo | Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period). | 18.6 Percent reduction |
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0027ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: <0.0001ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: <0.0001ANCOVA
Secondary
Percent Reduction in Number of Drop Seizures (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.
Time frame: 4-week baseline period and the last 4 weeks of the 12-week maintenance period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Clobazam Low Dose | Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period). | 31.8 Percent reduction |
| Clobazam Medium Dose | Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period). | 56.0 Percent reduction |
| Clobazam High Dose | Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period). | 68.0 Percent reduction |
| Placebo | Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period). | -0.1 Percent reduction |
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.1469ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0161ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0024ANCOVA
Secondary
Percent Reduction in Number of Drop Seizures (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.
Time frame: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Clobazam Low Dose | Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period). | 44.1 Percent reduction |
| Clobazam Medium Dose | Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period). | 38.8 Percent reduction |
| Clobazam High Dose | Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period). | 64.9 Percent reduction |
| Placebo | Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period). | 21.1 Percent reduction |
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.1041ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.2207ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0025ANCOVA
Secondary
Tolerance
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.
Time frame: 4-week baseline period and first 4/first 8 weeks of the maintenance period
Population: MITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clobazam Low Dose | Tolerance | ≥ 50% reduction - first 4 weeks of maintenance | 25 Participants |
| Clobazam Low Dose | Tolerance | ≥ 50% reduction - first 8 weeks of maintenance | 23 Participants |
| Clobazam Medium Dose | Tolerance | ≥ 50% reduction - first 8 weeks of maintenance | 38 Participants |
| Clobazam Medium Dose | Tolerance | ≥ 50% reduction - first 4 weeks of maintenance | 42 Participants |
| Clobazam High Dose | Tolerance | ≥ 50% reduction - first 4 weeks of maintenance | 38 Participants |
| Clobazam High Dose | Tolerance | ≥ 50% reduction - first 8 weeks of maintenance | 38 Participants |
| Placebo | Tolerance | ≥ 50% reduction - first 4 weeks of maintenance | 18 Participants |
| Placebo | Tolerance | ≥ 50% reduction - first 8 weeks of maintenance | 20 Participants |
Other Pre-specified
Percent Reduction in the Number of Non-drop Seizures.
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.
Time frame: 4-week baseline period and the 12-week maintenance period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Clobazam Low Dose | Percent Reduction in the Number of Non-drop Seizures. | -53.3 Percent reduction |
| Clobazam Medium Dose | Percent Reduction in the Number of Non-drop Seizures. | -3.3 Percent reduction |
| Clobazam High Dose | Percent Reduction in the Number of Non-drop Seizures. | 40.0 Percent reduction |
| Placebo | Percent Reduction in the Number of Non-drop Seizures. | -76.3 Percent reduction |
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.721ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.2505ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0924ANCOVA
Other Pre-specified
Percent Reduction of Total (Drop and Non-Drop) Seizures.
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.
Time frame: 4-week baseline period and 12-week maintenance period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Clobazam Low Dose | Percent Reduction of Total (Drop and Non-Drop) Seizures. | 34.8 Percent reduction |
| Clobazam Medium Dose | Percent Reduction of Total (Drop and Non-Drop) Seizures. | 45.3 Percent reduction |
| Clobazam High Dose | Percent Reduction of Total (Drop and Non-Drop) Seizures. | 65.3 Percent reduction |
| Placebo | Percent Reduction of Total (Drop and Non-Drop) Seizures. | 9.3 Percent reduction |
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0414ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: 0.0044ANCOVA
Comparison: ANCOVA with the percent reduction in drop seizures as the dependent variable and treatment, pooled center, and baseline drop seizure rate as the independent variables. A step-down procedure used, starting with the high dose versus placebo.p-value: <0.0001ANCOVA