Topiramate as Adjunctive Therapy in Infants 1-24 Months for the Control of Partial Onset Seizures

A Randomized, Double-Blind, Placebo-Controlled, Fixed Dose-Ranging Study to Assess the Safety, Tolerability, and Efficacy of Topiramate Oral Liquid and Sprinkle Formulations as an Adjunct to Concurrent Anticonvulsant Therapy for Infants (1-24 Months of Age) With Refractory Partial-Onset Seizures

The purpose of this study is to evaluate the tolerability, safety and efficacy of topiramate in infants with refractory partial onset seizures (POS).

This is a world wide, multicenter, randomized, double-blind, placebo-controlled study to evaluate the tolerability, safety and efficacy of 3 target doses (5, 15, and 25 mg/kg/day) of topiramate compared with placebo as an adjunct therapy in infants with refractory partial onset seizures (POS). There are 4 phases to the study, a screening phase of 3 days, a double blind treatment phase of 20 days, a one year open label extension phase and a posttreatment (taper and withdrawal) phase. The oral liquid formulation will also be assessed during this study, as it is investigational, unlike the marketed sprinkle formulation. 5, 15, 25 mg/kg/day of topriramate sprinkle and oral liquid formulation will be administered during the four phases of the study.

Video-recorded EEG was primary efficacy measure. Baseline vEEG and the vEEG at Visit 4 (Days 19 to 20; end point DB treatment phase or early withdrawal) will be read by a blinded central reader

Video-recorded EEG was primary efficacy measure. Baseline vEEG and the vEEG at Visit 4 (Days 19 to 20; end point DB treatment phase or early withdrawal) will be read by a blinded central reader

Percent treatment responders >=50% reduction seizure rate. ·Percentage change in seizure rate recorded on subject take-home records. Percentage change in seizure rates for all seizure types recorded on VEEG.

Inclusion Criteria: 1-24 months, inclusive Concurrent 1 or 2 antiepileptic drugs Receiving regular enteral feedings Weigh between 3.5 and 15 kg Clinical or EEG evidence of simple or complex POS Exclusion Criteria: Exclusively breast fed and cannot take medicine by mouth Surgically implanted and functioning vagus nerve stimulator Renal stones Medically uncontrolled illnesses or conditions Infantile seizures as a result of a correctable medical condition Progressive neurologic disorder

Novotny E, Renfroe B, Yardi N, Nordli D, Ness S, Wang S, Weber T, Kurland CL, Yuen E, Eerdekens M, Venkatraman L, Nye JS, Ford L. Randomized trial of adjunctive topiramate therapy in infants with refractory partial seizures. Neurology. 2010 Mar 2;74(9):714-20. doi: 10.1212/WNL.0b013e3181d1cd4c. Epub 2010 Jan 20.

Ness S, Todd MJ, Wang S, Eerdekens M, Nye JS, Ford L. Adaptive behavior outcomes in infants treated with adjunctive topiramate. Pediatr Neurol. 2012 Jun;46(6):350-8. doi: 10.1016/j.pediatrneurol.2012.02.028.

Puri V, Ness S, Sattaluri SJ, Wang S, Todd M, Yuen E, Eerdekens M, Nye JS, Manitpisitkul P, Shalayda K, Ford L. Long-term open-label study of adjunctive topiramate in infants with refractory partial-onset seizures. J Child Neurol. 2011 Oct;26(10):1271-83. doi: 10.1177/0883073811406982. Epub 2011 Jun 14.

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=460&filename=CR002233_CSR.pdf