E. Ciafaloni, F. Cohen, R. Griggs
Apr 10, 2018
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Journal
Neurology
Abstract
Objective: Compare effects of dichlorphenamide in adolescent and adult patients with primary periodic paralysis (PP). Background: Dichlorphenamide is approved for use in adults with PP (≤200 mg/day) based on two controlled studies; one enrolled adolescents. Results in adolescents have not been previously described. Design/Methods: In a Phase 3, placebo-controlled, crossover study (Tawil et al, Ann Neurol , 2000), after an 8-week run-in phase, 73 patients age ≥10 years (mean 37) were randomly assigned to receive dichlorphenamide or placebo for 9 weeks, followed by washout (≥9 weeks) and a switch to the other treatment for 9 weeks. This post-hoc analysis of study records compared effects of dichlorphenamide on weekly attack rates, weekly severity-weighted attack rates, and frequency of nine prespecified adverse events (AEs) between adolescents and adults. Results: Seven of 73 patients were aged 10–17: one (age 10) withdrew prior to receiving dichlorphenamide, one (age 17) provided tolerability data only, 5 (ages 13–17) provided efficacy and tolerability data. All but one adolescent (50 mg BID) was treated with 100 mg BID. Twenty-eight adult patients provided complete attack-rate data. The self-reported age of onset (10–11 years) and characteristics of attacks were similar across age groups at baseline. Dichlorphenamide treatment resulted in median changes from baseline in weekly attack rate of −0.96 [CI: −1.46, −0.68] in adolescents vs −0.83 [CI: −2.58, −0.67] in adults. Median changes from baseline in severity-weighted weekly attack rate were −2.25 [CI: −3.37, −1.41] in adolescents vs −1.17 [CI: −4.95, −0.81] in adults. Three adolescents reported ≥1 AE during dichlorphenamide treatment, all of which were known class effects. None was dose-limiting or resulted in study withdrawal. The frequency of each reported AE was comparable across age groups. Conclusions: Adolescents and adults with PP had similar improvement in short-term attack rates and AEs with dichlorphenamide within the approved dosing range. Study Supported by: Strongbridge Biopharma Disclosure: Dr. Ciafaloni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sarepta, Santhera. Dr. Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Strongbridge Biopharma. Dr. Cohen holds stock and/or stock options in Strongbridge Biopharma. Dr. Griggs has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Serve on DSMB for PTC Therapeutics, Idera Pharma; consultant for Saretpta, Marathon, Strongbridge and Taro Pharma. Dr. Griggs has received personal compensation in an editorial capacity for Correspondence editor for Neurology. Dr. Griggs has received royalty, license fees, or contractual rights payments from Royalties from Marathon and PTC Pharmaceuticals. Dr. Griggs has received research support from Research support from Marathon, PTC.