A phase 3 trial of extended release oral dalfampridine in multiple sclerosis

Abstract

Objective A previous phase 3 study showed significant improvement in walking ability in multiple sclerosis (MS) patients treated with oral, extended‐release dalfampridine (4‐aminopyridine) 10mg twice daily. The current study was designed to confirm efficacy and further define safety and pharmacodynamics. Methods This was a 39‐center, double‐blind trial in patients with definite MS of any course type. Participants were randomized to 9 weeks of treatment with dalfampridine (10mg twice daily; n = 120) or placebo (n = 119). Response was defined as consistent improvement on the Timed 25‐Foot Walk, with percentage of timed walk responders (TWRs) in each treatment group as the primary outcome. The last on‐treatment visit provided data from 8 to 12 hours postdose, to examine maintenance of effect. Results One patient from each group was excluded from the modified Intention to Treat population. The proportion of TWRs was higher in the dalfampridine group (51/119 or 42.9%) compared to the placebo group (11/118 or 9.3%, p < 0.0001). The average improvement in walking speed among dalfampridine‐treated TWRs during the 8‐week efficacy evaluation period was 24.7% from baseline (95% confidence interval, 21.0–28.4%); the mean improvement at the last on‐treatment visit was 25.7%, showing maintenance of effect over the interdosing period. There were no new safety findings. Interpretation This interventional study provides class 1 evidence that dalfampridine extended‐release tablets produce clinically meaningful improvement in walking ability in a subset of people with MS, with the effect maintained between doses. Ann Neurol 2010;68:494–502