Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).

Study Overview
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Brief Summary
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The objective of study is to assess the clinical improvement (change in seizure frequency), safety, and tolerability of subjects with partial seizures following adjunctive therapy of pregabalin BID (150 to 600 mg/day titration) in addition to existing standards AEDs.

Official Title
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Lyrica (Pregabalin) Administered As An Add-On Therapy For Partial Seizures (LEADER) An Open-Label, Multicenter Add-On Therapy Trial

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients equal to or greater than 18 years of age with diagnosis of epilepsy with partial seizures having minimum of two partial seizures during a two month period before the baseline visit Having a clinical history of epilepsy and AED treatment at least 1 year prior to inclusion Exclusion Criteria: AED or Seizures/Epilepsy Related Exclusions:having a treatable cause of seizures Having absences seizures Having had status epileptics within the year prior to inclusion Having a progressive neurological or systematic disorder Having known significant renal or hepatic dysfunction

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Pregabalin|Pregabalin treatment, given as 2 divided doses, is initiated at a dose of 150 mg/day (75 mg BID). Based on individual subject response and tolerability, the dosage may be increased to 300 mg/day after 1 week (150 mg BID given as two 75-mg capsules BID). Based on subjects individual response and tolerability, dosage can be incrementally increased further after an additional week to 600 mg/day (300 mg BID given as four 75-mg capsules BID).|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period | Percentage change from baseline=[(12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate)/ 8 week baseline period seizure frequency rate] x 100. Seizure frequencies per 28-day period: = (total # of partial seizures in period x 28 / (total # of days in period). | 8 week baseline period & 12 week treatment observation period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period. | Percentage change from baseline = ((21 weeks-8 weeks)/8 weeks)*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency. | 8 week baseline period and 21 week treatment period | 
| Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. | Percentage change from baseline = [(4 week seizure frequency minus 8 week baseline) / (8 week baseline seizure frequency)] x 100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency. | 8 week baseline period and 21 week treatment period | 
| Number of Subjects Seizure-free | Count of subjects seizure free during the period. | last 4 weeks & whole 12 week treatment observation period | 
| Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period. | Number of subjects with at least a 50% or 75% reduction in partial seizure frequency between baseline and treatment period. | 8 week baseline observation period & last 4 weeks of observation period | 
| Subjects Achieving Seizure Freedom During Observation Period | Number of subjects achieving seizure freedom (no seizures) during last 4 weeks or duration of 12 week observation period. | Day 147 from the first dose of study drug | 
| Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency | Percentage change from baseline = ((12 weeks - 8 weeks)/8 weeks)*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency. | 8 week baseline observation period & 12 week treatment observation period | 
| Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) | The PGIC is a patient-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). | End of 21-week treatment | 
| Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) | The CGIC is a clinician's judgment of the overall change in the patient's condition over a defined period on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). | End of 21-week treatment | 
| Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores | Subjects recall sleep related activities over the previous 4 weeks. Low scores reflect greater impairment (except sleep adequacy, optimal sleep, &quantity). Range = 0 - 100 for Sleep Disturbance, Snoring, Awaken Short of Breath, Sleep Adequacy, Somnolence, & Sleep Problems Index. Quantity of Sleep Range = 0 - 24. Optimal Sleep Range 0 - 1. | Baseline, end of 21-week treatment | 
| Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21. | Change in total HADS score between Baseline and Week 21. Each of the 14 items is scored 0, 1, 2 or 3 where a score of 3 corresponds to the most anxious/depressed. 7-item depression and 7-item anxiety subscales are summed; each resulting in a total score of 0-21. | Baseline, End of 21-week treatment | 
| Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline | Count of subjects with a weight gain of at least 7 percent relative to baseline. | Baseline, End of 21-week treatment | 
| Subjects Assessment of Optimal Sleep | Number of subjects that responded optimal or non-optimal sleep in Optimal Sleep subscale of Medical Outcomes Study (MOS) Sleep scale. | Baseline, End of 21-week treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregabalin for partial seizures