Abstract 150: Dalfampridine in Patients With Chronic Post-Ischemic Stroke Deficits: Results From a Phase 2 Study

Abstract

Objective: To evaluate the safety and tolerability of dalfampridine extended release tablets (D-ER; prolonged-release fampridine in Europe) 10 mg twice daily administered to patients with chronic post-ischemic stroke deficits, and to perform an exploratory assessment on sensorimotor function. Background: Ischemic stroke is a major cause of sensorimotor deficits that may lead to persistent disability, such as walking impairment. Methods: The study design included 2-wk screening, 2-wk treatment, 1-wk placebo (PBO) washout and crossover, 2-wk treatment, and 1-wk follow-up. Patients with a history of ischemic stroke ≥6 months prior to enrollment, with stable sensorimotor deficits and Fugl-Meyer Assessment lower extremity motor score ≤28, and who were able to complete the Timed 25-foot walk (T25FW) were eligible. Patients were randomized into 2 sequences: A (PBO/D-ER) or B (D-ER/PBO). Safety was the primary endpoint. Walking speed assessed by T25FW was the prespecified key efficacy exploratory outcome. Potential changes in community ambulation categories were based on walking speed. Results: Patient (N=83) demographics were comparable except for age, which varied significantly between sequences (mean [SE]: A=57.5 [1.31]; B=63.5 [1.68]; P =0.008). Seventy subjects (84.3%) completed the study with 6 withdrawals for adverse events (AEs). Treatment emergent AE rates were 55% for D-ER and 37% for PBO; most common were dizziness, nausea, and fatigue. Four subjects (2/treatment) had serious AEs including 3 seizures; 1 PBO and 2 D-ER one of which was secondary to an intentional overdose. The overall change in T25FW speed from baseline was greater with D-ER relative to PBO (0.21 vs 0.10 ft/sec; N=78; P =0.027). Based on walking speed, there was a near 2-fold increase in those who shifted from household to limited community ambulation and from limited to full community ambulation in the D-ER versus PBO groups (15.3% vs 7.7%, respectively). Conclusions: Results suggest that D-ER is well tolerated and may improve walking in patients with chronic post-ischemic stroke deficits. These data provide a foundation for larger efficacy and safety studies in this population.