Dalfampridine in chronic sensorimotor deficits after ischemic stroke: A proof of concept study.

Abstract

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. 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. 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). 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.