L.N.M. was responsible for statistical analysis.
Article first published online: 25 OCT 2010
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 68, Issue 4, pages 494–502, October 2010
How to Cite
Goodman, A. D., Brown, T. R., Edwards, K. R., Krupp, L. B., Schapiro, R. T., Cohen, R., Marinucci, L. N., Blight, A. R. and on behalf of the MSF204 Investigators (2010), A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Ann Neurol., 68: 494–502. doi: 10.1002/ana.22240
Presented in part at the World Congress on Treatment and Research in Multiple Sclerosis, Montreal, Quebec, Canada, September 20, 2008.
The MS-F204 Investigators are listed in the Appendix.
The following individuals served as members of the independent Data Monitoring Committee: Dr J. Selzer (chair), Dr B. Greenberg, Dr A. Hartman, and A. Smith (statistician).
- Issue published online: 25 OCT 2010
- Article first published online: 25 OCT 2010
- Manuscript Accepted: 27 AUG 2010
- Manuscript Revised: 19 AUG 2010
- Manuscript Received: 27 JAN 2010
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.
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.
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.
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