David M. Simpson, James Goldenberg, Scott Kasner, Marshall Nash, Michael J. Reding, Richard M. Zweifler, Gustavo Suarez, Ping Zhao, Herbert R. Henney III, Adrian L. Rabinowicz, Enrique Carrazana
Mount Sinai Medical Center, Department of Neurology, Box 1052, New York, NY 10029, USA. E-mail: david.simpson@mssm.edu
DOI: 10.2340/16501977-2033

Objective: To evaluate the safety and tolerability of dalfampridine extended release (D-ER) in participants with chronic post-ischemic stroke deficits, and to assess for potential drug activity on sensorimotor function.
Methods: Using a double-blind, placebo-controlled, cross-over design, participants were randomized to placebo/D-ER or D-ER/placebo sequences and given D-ER 10 mg or placebo twice daily. Key inclusion criteria were: ischemic stroke ≥ 6 months, Fugl-Meyer Assessment lower extremity motor score ≤ 28, ability to complete Timed 25-Foot Walk (T25FW). The primary outcome was safety and tolerability. The key exploratory measure was walking speed (T25FW). Other assessments were: Box and Block, and Grip and Pinch tests; Functional Independence Measure. Full-crossover data were analyzed using mixed-effects model.
Results: A total of 83 participants were randomized: 70 completed and 13 discontinued the study. Adverse events were consistent with previous D-ER trials; no new safety signals were observed. Four participants experienced serious adverse events: 3 seizures (1 placebo, 2 D-ER), 1 was secondary to intentional overdose. Most common treatment-emergent adverse events were: dizziness, nausea, arthralgia and fatigue. Mixed-effects analysis showed an effect for D-ER vs placebo in improving walking speed (0. 21 vs 0. 10 ft/s; p = 0. 027).
Conclusions: D-ER was generally well tolerated in participants with chronic stroke deficits. Potential drug activity on lower extremity sensorimotor function, with an improvement in walking speed, was seen.