A Study of the Efficacy and Safety of Pregabalin as Add-On Therapy for Partial Onset Seizures in Children Ages 4-16 Years

Study Overview
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Brief Summary
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Study A0081041 is a double blind, placebo controlled, randomized, parallel group, multicenter study to evaluate the safety and efficacy of two dose levels of pregabalin administered in equally divided daily doses, in either capsule or oral liquid formulation, as adjunctive therapy in pediatric subjects 4 to 16 years of age with partial onset seizures.

Official Title
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A DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER STUDY OF THE EFFICACY AND SAFETY OF PREGABALIN AS ADJUNCTIVE THERAPY IN CHILDREN 4 -16 YEARS OF AGE WITH PARTIAL ONSET SEIZURES

Conditions
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Epilepsy, Partial Seizures

Intervention / Treatment
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* Drug: Pregabalin add-on therapy
* Drug: Pregabalin add-on therapy
* Drug: Pregabalin add-on therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects and/or parent(s)/legally acceptable representative must be considered willing and able to sign consent, and complete daily seizure diaries and monitor seizure frequency. Male and female epilepsy subjects, 4 to 16 years of age inclusive on the date of the Screening Visit. Diagnosis of epilepsy with partial onset seizures classified as simple partial, complex partial or partial becoming secondarily generalized, according to the International League Against Epilepsy (ILAE) Diagnosis criteria. Must have a partial onset seizure frequency of at least 3 seizures per 28 day period prior to screening. Must have a partial onset seizure frequency of at least 6 seizures and no continuous 4 week seizure free period during the 8 week baseline phase prior to randomization. Currently receiving a stable dose of 1 to 3 antiepileptic drugs (stable within 28 days prior to screening). Exclusion Criteria: Primary generalized seizures (including in the setting of co-existing partial onset seizures) which include, for example: Clonic, tonic and clonic-tonic seizures (note that partial onset seizures that become secondarily generalized are not exclusionary); Absence seizures; Infantile spasms; Myoclonic, myoclonic atonic, myoclonic tonic seizures. Lennox Gastaut syndrome, Benign Epilepsy with Centrotemporal Spikes (BECTS) and Dravet syndrome. A current diagnosis of febrile seizures, or seizures related to an ongoing acute medical illness. Any febrile seizures within 1 year of screening. Status epilepticus within 1 year prior to screening. Seizures related to drugs, alcohol, or acute medical illness. Any change in AED regimen (type of medication or dose) within 28 days of the Screening Visit or during the Baseline Phase. Progressive structural CNS lesion or a progressive encephalopathy.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Pregabalin add-on therapy<br>* Subjects will be randomized to receive a fixed dose of either placebo, pregabalin Level 1 (maximum 150 mg/day) or pregabalin Level 2 (maximum 600 mg/day) in a 1:1:1 ratio, in addition to the subjects current AED medication regimen. Either capsules or oral liquid form will be administered, depending on subjects preference and ability to swallow capsules, in two equally divided daily doses. The study will have an 8 week baseline period; a 2 week dose escalation period; a 9 week dose maintenance period; and a 1 week dose taper period.<br>|
| Experimental: Pregabalin Level 1 (max 150 mg/day)<br> | Drug: Pregabalin add-on therapy<br>* Subjects will be randomized to receive a fixed dose of either placebo, pregabalin Level 1 (maximum 150 mg/day) or pregabalin Level 2 (maximum 600 mg/day) in a 1:1:1 ratio, in addition to the subjects current AED medication regimen. Either capsules or oral liquid form will be administered, depending on subjects preference and ability to swallow capsules, in two equally divided daily doses. The study will have an 8 week baseline period; a 2 week dose escalation period; a 9 week dose maintenance period; and a 1 week dose taper period.<br>|
| Experimental: Pregabalin Level 2 (max 600 mg day)<br> | Drug: Pregabalin add-on therapy<br>* Subjects will be randomized to receive a fixed dose of either placebo, pregabalin Level 1 (maximum 150 mg/day) or pregabalin Level 2 (maximum 600 mg/day) in a 1:1:1 ratio, in addition to the subjects current AED medication regimen. Either capsules or oral liquid form will be administered, depending on subjects preference and ability to swallow capsules, in two equally divided daily doses. The study will have an 8 week baseline period; a 2 week dose escalation period; a 9 week dose maintenance period; and a 1 week dose taper period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log-Transformed 28-Day Seizure Rate For All Partial Onset Seizures During Baseline Phase | All partial onset seizures experienced during baseline phase were recorded by the participants or their parents/legal guardian, in a daily seizure diary. 28-day seizure rate for all partial onset seizures = ([number of seizures in the baseline phase] divided by [number of days in baseline phase minus {-} number of missing diary days in baseline phase])*28. For log-transformation, the quantity 1 was added to the 28-day seizure rate for all participants to account for any possible 0 seizure incidence. This resulted in final calculation as: log transformed (28-day seizure rate +1). | Baseline phase (up to 8 weeks prior to treatment phase [Day 1]) | 
| Log-Transformed 28-Day Seizure Rate For All Partial Onset Seizures During 12-Week Treatment Phase | All partial onset seizures experienced during treatment phase were recorded by the participants or their parents/legal guardian in a daily seizure diary. 28-day seizure rate for all partial onset seizures = ([number of seizures in the treatment phase] divided by [number of days in treatment phase minus {-} number of missing diary days in treatment phase])*28. For log-transformation, the quantity 1 was added to the 28-day seizure rate for all participants to account for any possible 0 seizure incidence. This resulted in final calculation as: log transformed (28-day seizure rate +1). | Day 1 up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least 50 Percent (%) or Greater Reduction From Baseline in 28-day Seizure Rate During the 12 Week Treatment Phase | Percentage of participants with 50 percent (%) or greater reduction from baseline in 28-day seizure rate during the 12 week treatment phase were reported. 28-day seizure rate for all partial onset seizures = ([number of seizures in the treatment phase] divided by [number of days in treatment phase minus {-} number of missing diary days in treatment phase])*28. | Day 1 up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, efficacy, partial onset seizures, pediatric, pregabalin, placebo-controlled, double-blind