An Open Label Study of Levetiracetam Monotherapy in Patients With Newly Diagnosed Focal Epilepsy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of Levetiracetam (LEV) used as monotherapy, with efficacy measured as 6-month seizure freedom at the last evaluated dose in the LEV 1000 mg/day to 2000 mg/day group, in newly or recently diagnosed epilepsy subjects.

Official Title
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An Open-label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Levetiracetam Used as Monotherapy in Newly or Recently Diagnosed Epilepsy Patients Aged Older Than or Equal to 16 Years With Partial Seizures

Conditions
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Epilepsy, Partial Onset Seizures

Intervention / Treatment
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* Drug: Levetiracetam (LEV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is male or female and aged ≥ 16 years at Visit 1 Subjects with newly or recently diagnosed Epilepsy having experienced unprovoked Partial Seizures (IA, IB, IC), that are classifiable according to the International League Against Epilepsy (ILAE) classification of Epileptic Seizures Subjects with at least 2 unprovoked seizures separated by a minimum of 48 hours in the year prior to Visit 1, of which, at least 1 unprovoked seizure occurred in the 3 months prior to Visit 1 Minimum body weight of 40 kg at Visit 1 Exclusion Criteria: Subject has a history or presence of seizure types other than partial (IA, IB, IC) Subject has an experience of any type of brain surgery in the consecutive 2 years prior to Visit 1 Subject has a history or presence of known Pseudo-Seizures Subject has been treated for Epilepsy with any Antiepileptic Drug (AED) within the 6 months prior to Visit 1. However, acute and sub-acute seizure treatments are accepted for a maximum use of 2 weeks, if the treatments are stopped for the week prior to Visit 1 Subject has a known clinically significant acute or chronic illness, such as but not restricted to: cardiac, renal, hepatic dysfunction, endocrinological, or psychiatric illness, and that may impair reliable participation in the study or necessitate the use of medication not allowed by the protocol

Ages Eligible for Study
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Minimum Age: 16 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam 1000 mg/day to 2000 mg/day group<br>Subjects in the LEV 1000 mg/day to 2000 mg/day group receive the initial dose of LEV 1000 mg/day for the 1- week Stabilization Period and enter the Evaluation Period. Unless a seizure occurs during the Evaluation Period, the subjects will continue LEV 1000 mg/day for 26 weeks. If a seizure occurs during the Evaluation Period, the dose will be increased to 2000 mg/day and a restart of stabilization on LEV 2000 mg/day for 1 week is required prior to restarting the 26-weeks Evaluation Period on LEV 2000 mg/day. The LEV dose could be decreased as a fallback option at the investigator's discretion, if the subject did not tolerate the LEV dosage, as evidenced by the development of an AE. The fallback option was permitted to be performed once for subjects on LEV 2000 mg/day at any time during the restarted Stabilization Period (SP), restarted Evaluation Period (EP), or Maintenance Period (MP), as well as for subjects on LEV 3000 mg/day at any time during the SP, EP, or MP. | Drug: Levetiracetam (LEV)<br>* Active Substance: Levetiracetam Pharmaceutical Form: Film-coated tablet Concentration: LEV 250 mg, LEV 500 mg Frequency: Twice daily Route of Administration: Oral use<br>* Other names: E Keppra;|
| Experimental: Levetiracetam 3000 mg/day group<br>Unless a seizure occurs, the subjects in this arm will continue LEV 3000 mg/day for 26 weeks. Subjects in the LEV 3000 mg/day group undergo a 4-week Up-Titration Period prior to the 1-week Stabilization Period. They receive 1000 mg/day for 2 weeks and 2000 mg/day for 2 weeks during the Up-Titration Period and LEV 3000 mg/day for 1 week during the Stabilization Period. The LEV dose could be decreased as a fallback option at the investigator's discretion, if the subject did not tolerate the LEV dosage, as evidenced by the development of an AE. The fallback option was permitted to be performed once for subjects on LEV 2000 mg/day at any time during the restarted Stabilization Period (SP), restarted Evaluation Period (EP), or Maintenance Period (MP), as well as for subjects on LEV 3000 mg/day at any time during the SP, EP, or MP. | Drug: Levetiracetam (LEV)<br>* Active Substance: Levetiracetam Pharmaceutical Form: Film-coated tablet Concentration: LEV 250 mg, LEV 500 mg Frequency: Twice daily Route of Administration: Oral use<br>* Other names: E Keppra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects in the Levetiracetam (LEV) 1000 mg/Day to 2000 mg/Day Group Who Are Seizure Free for 26 Consecutive Weeks of Treatment During the Evaluation Period | A subject was considered seizure free, if no seizure occurred during the 6 consecutive months (26 weeks) in the Evaluation Period. If one of the following occurred, the subject was not considered seizure free: A documented seizure during 6 consecutive months of the Evaluation Analysis Period Subject discontinued the study prematurely during the Evaluation Analysis Period Missing Seizure Count Case Report Forms (CRFs) prior to completing the Evaluation Analysis Period. | From the end of the 1-week Stabilization Period over the 26-weeks Evaluation Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Seizure at the Last Evaluated Dose in Subjects in the Levetiracetam (LEV) 1000 mg/Day to 2000 mg/Day Group | Time was measured from first day of last evaluated dose. Seizures during Stabilization were not considered. The Median time to first seizure will be estimated from the Kaplan-Meier curve. | During Evaluation, Maintenance and Safety Follow Up Period after 1-week Stabilization Period, assessed up to 1 year | 
| Time to Withdrawal at the Last Evaluated Dose in Subjects in the Levetiracetam (LEV) 1000 mg/Day to 2000 mg/Day Group | Median time to withdrawal will be estimated from the Kaplan-Meier curve. | During 1-week Stabilization Period, Evaluation, Maintenance and Safety Follow Up Period, assessed up to 1 year | 
| Time to First Seizure in Subjects in the Levetiracetam (LEV) 3000 mg/Day Group | Time was measured from first day of last evaluated dose. Seizures during Stabilization were not considered. The Median time to first seizure will be estimated from the Kaplan-Meier curve. | During Evaluation, Maintenance and Safety Follow Up Period after 1-week Stabilization Period, assessed up to 1 year | 
| Time to Withdrawal in Subjects in the Levetiracetam (LEV) 3000 mg/Day Group | Median time to withdrawal will be estimated from the Kaplan-Meier curve. | During 1-week Stabilization Period, Evaluation, Maintenance and Safety Follow Up Period, assessed up to 1 year | 
| Percentage of Subjects in the Levetiracetam (LEV) 1000 mg/Day to 2000 mg/Day Group Who Are Seizure Free for 52 Consecutive Weeks of Treatment During the Evaluation Period and the Maintenance Period | Subjects who complete the 26-weeks Evaluation Period without having a seizure will continue receiving the same dose of LEV as in the Evaluation Period during the 26-weeks Maintenance Period unless a seizure occurs. | From entry in the 26-weeks Evaluation Period to the end of the 26-weeks Maintenance Period | 
| Percentage of Subjects in the Levetiracetam (LEV) 3000 mg/Day Group Who Are Seizure Free for 26 Consecutive Weeks of Treatment During the Evaluation Period | A subject was considered seizure free, if no seizure occurred during the 6 consecutive months (26 weeks) in the Evaluation Period. If one of the following occurred, the subject was not considered seizure free: A documented seizure during 6 consecutive months of the Evaluation Analysis Period Subject discontinued the study prematurely during the Evaluation Analysis Period Missing Seizure Count Case Report Forms (CRFs) prior to completing the Evaluation Analysis Period. | From the end of the 1-week Stabilization Period over the 26-weeks Evaluation Period | 
| Percentage of Subjects in the Levetiracetam (LEV) 3000 mg/Day Group Who Are Seizure Free for 52 Consecutive Weeks of Treatment During the Evaluation Period and the Maintenance Period | Subjects who complete the 26-weeks Evaluation Period without having a seizure will continue receiving LEV 3000 mg/day during the 26-weeks Maintenance Period unless a seizure occurs. | From entry in the 26-weeks Evaluation Period to the end of the 26-weeks Maintenance Period |