A double-blind, randomized, controlled study of two dose strengths of dalfampridine extended release on walking deficits in ischemic stroke

Abstract

Background: Stroke-induced ischemia affects both cortex and underlying white matter. Dalfampridine extended release tablets (D-ER) enhance action potential conduction in demyelinated axons, which may positively affect post-stroke recovery.

Objective: Based on promising preliminary data, we compared efficacy of D-ER administered at 7.5 mg or 10 mg with placebo on post-stroke ambulation. Primary study outcome (response) was a ≥20% increase on the 2-minute walk test (2 MinWT) at 12 weeks after first drug administration.

Methods: This was a multicenter, randomized, placebo-controlled, 3-arm, parallel-group, safety and efficacy trial. After obtaining baseline measures of 2 MinWT, Walk-12, and Timed Up and Go, subjects entered a 2-week, single-blind placebo run-in period and were randomized 1:1:1 to receive 7.5 mg D-ER, 10 mg D-ER, or placebo, dosed twice-daily for 12 weeks. Follow-up evaluations occurred at weeks 14 and 16 when subjects were off study drug.

Results: The study was terminated early with 377 of planned 540 patients enrolled, due to no treatment effect. At week 12, mean increase in distances walked in 2 minutes were similar among the 3 study groups (14.9±40.0 feet; 19.4±39.6 feet; and 20.4±38.3 feet for placebo, 7.5 mg D-ER, and 10 mg D-ER, respectively). The proportion of subjects who showed ≥20% improvement on 2 MinWT at week 12 was 13.5%, 14.0%, and 19.0%, for placebo, 7.5 mg D-ER, and 10 mg D-ER, respectively; these were nonsignificant changes from baseline for all groups.

Conclusions: D-ER at either a 7.5-mg or 10-mg dose did not significantly increase performance on the 2 MinWT in stroke survivors with gait impairment, although this study was terminated early before full enrollment. (Clinical Trial # NCT02271217).

Keywords: ambulation; hemiplegia; lower extremity; rehabilitation; stroke.

Conflict of interest statement

Stephen J. Page received grant support for the conduct of this trial from Acorda Therapeutics.

Scott E. Kasner received grant support for the conduct of this trial from Acorda Therapeutics.

Marcia Bockbrader received grant support for the conduct of this trial from Acorda Therapeutics.

Mark Goldstein has received grant funding for Acorda Therapeutics clinical trials for Eli Lilly, Biogen, Genentech, Roche, Sunovion, Pfizer, and Novartis.

Seth P. Finklestein received grant support for the conduct of this trial from Acorda Therapeutics, andis a Consultant to Constant Pharmaceuticals, NeuroVasc, and AZTherapies, and is a Principal at Stemetix.

MingMing Ning participated in this clinical trial supported by Acorda Therapeutics.

Waleed El-Feky received grant support for the conduct of this trial from Acorda Therapeutics, and is a speaker for Allergan.

Christina A. Wilson has received royalties for stroke-related articles from UpToDate and Medlink Neurology.

Holly Roberts is an employee of, and owns stock in, Acorda Therapeutics, Inc.

Figures

Fig.1

Study design. DB, double blind; D-ER, dalfampridine extended release.

Fig.2

MILESTONE patient disposition. DB, double blind; D-ER, dalfampridine extended release.