Conversion to Monotherapy Study With Keppra XR for Partial Seizures

Study Overview
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Brief Summary
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The primary objective of this study is to assess the efficacy of two doses of Keppra XR compared with a historical control as the placebo, in the monotherapy treatment of partial onset seizures.

Official Title
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A Multi-center, Double-blind, Historical Control, Randomized Conversion to Monotherapy Study With Keppra XR for Treatment of Partial Onset Seizures

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Keppra XR
* Drug: Keppra XR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 12 to 75 years of age. Subjects must have inadequately controlled partial onset epilepsy. Subjects must be experiencing 2 to 40 seizures per 4-week period while being maintained on one or two standard AED(s) Exclusion Criteria: A history of status epilepticus in the 6 months preceding randomization. Significant medical, psychiatric or neurological illness. Intake of benzodiazepines on more than an occasional basis History of previous treatment with levetiracetam or sensitivity to levetiracetam.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Keppra XR 1000 mg/day<br>1000 mg/day once daily for 18 weeks (administered as two levetiracetam XR tablets and two placebo tablets once daily) | Drug: Keppra XR<br>* Administered as two 500 mg tablets (1000 mg) and two placebo tablets once daily for 18 weeks<br>|
| Experimental: Keppra XR 2000 mg/day<br>2000 mg/day once daily for 18 weeks (administered as four levetiracetam XR tablets once daily) | Drug: Keppra XR<br>* Administered as four 500 mg tablets (2000 mg) once daily for 18 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Cumulative Exit Rate at 112 Days After the Beginning of the Previous Antiepileptic Drug (AED) Tapering Phase | Cumulative exit rate at day 112, based on the duration between start date of previous AED tapering to the earliest date exit criterion was met; calculated using Kaplan Meier Methods. Subjects prematurely discontinued for reasons unrelated to exit criteria were censored as of last dose of study drug. Subjects who completed without meeting exit criteria were censored at Day 112. Exit criteria include increase in seizure frequency, severity, duration, status epilepticus, or new generalized seizure. Upper 95% 2-sided confidence limit for exit rate is compared to the historical control rate: 0.678. | 112 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Cumulative Rate of Exit Events, Which Include Discontinuation Due to Exit Criteria, Withdrawal Due to Adverse Events (AE) and Withdrawal Due to Lack of Efficacy, at 112 Days After the Beginning of Previous Antiepileptic Drug (AED) Tapering Phase | The cumulative exit event rate at Day 112 was calculated using Kaplan Meier methods. The exit event rate estimate was based on the duration between the start date of previous AED tapering to the earliest date an exit event occured. Subjects who prematurely discontinued for reasons unrelated to exit criteria, adverse event, or lack of efficacy were censored as of the last dose of study medication. Subjects who completed the study without having an exit event were censored as of Day 112. | 112 days | 
| The Cumulative Rate of Exit Events Due to Any Reasons at 112 Days After the Beginning of Previous Antiepileptic Drug (AED) Tapering Phase | The cumulative exit event rate at Day 112 was calculated using Kaplan Meier methods. The exit event rate estimate was based on the duration between the start date of previous AED tapering to the earliest date an exit event occured. Subjects who completed the study without having an exit event were censored as of Day 112. | 112 days | 
| The Cumulative Exit Rate at 112 Days for the Keppra XR 1000 mg Group After the Beginning of the Previous Antiepileptic Drug (AED) Tapering Phase | Keppra XR 1000 mg arm was not intended for inferential analysis (planned 3 to 1 randomization, Keppra XR 2000 mg: 1000 mg). The Exit Rate was based on the duration between the start date of previous AED tapering to the earliest date an exit crterion was met. Subjects who prematurely discontinued for reasons unrelated to exit criteria were censored as of the last dose of study medication. Subjects who completed the study without meeting an exit criterion were censored as of Day 112. | 112 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Keppra XR, conversion to monotherapy, partial seizures