Effects of 5mg and 10mg Dalfampridine Extended Release Tablets on 6-Minute Walk Distance in People with Multiple Sclerosis: A Subgroup Analysis of a Double-Blind, Placebo-Controlled Trial (S01.007)

OBJECTIVE: To evaluate the effects of dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine outside the US) 5mg and 10mg twice daily in a subgroup of patients at sites that performed the 6 Minute Walk (6MW) test, which measures distance walked as fast as possible in 6 minutes, and is often considered a measure of walking endurance. BACKGROUND: Dalfampridine-ER 10mg tablets, twice daily, are approved to improve walking in patients with multiple sclerosis (MS). A study comparing dalfampridine-ER 5mg and 10mg tablets was required as an FDA post-marketing commitment. A subset of sites included the 6MW test as a pre-specified secondary endpoint in addition to the primary endpoint based on the Timed 25-Foot Walk (T25FW). DESIGN/METHODS: Participants were randomized to 4-week, double-blind, twice-daily treatment with dalfampridine-ER 5mg (n=144), 10mg (n=143), or placebo (n=143). This analysis reports 6MW data for the subset of subjects who completed these assessments (n=49, placebo; n=53, dalfampridine-ER 5mg; n=51, dalfampridine-ER 10mg). The 6MW test was administered once before treatment, and once after 2 weeks on treatment. Treatment effects were compared using an ANOVA model, with change from baseline as the dependent variable and baseline and treatment as independent variables. RESULTS: For subjects who completed the 6MW, demographic characteristics and baseline efficacy variables were not significantly different among treatments; baseline 6MW distance (mean±SE) was 847.4±58.0 ft for placebo, 840.2±44.3 ft for dalfampridine-ER 5mg, and 860.7±45.0 ft for dalfampridine-ER 10mg. While the 2-week change from baseline (mean±SE) in walking distance was numerically higher with dalfampridine-ER 5mg (76.8±27.3 ft) relative to placebo (41.7±23.4 ft), the difference was not significant ( P =0.308). However, the improvement on the 6MW with dalfampridine-ER 10 mg (128.6±21.7 ft) was significantly greater than placebo ( P =0.014). CONCLUSIONS: In these subjects with MS, twice daily dalfampridine-ER 10mg but not 5mg significantly improved 6MW distance relative to placebo. Supported by: Acorda Therapeutics, Inc. Disclosure: Dr. Applebee has nothing to disclose. Dr. Goodman has received personal compensation for activities with Acorda Therapeutics, Avanir, Biomarin, Biogen Idec, EMD Serono, Genzyme, Novartis, Pfizer, and Teva as a consultant. Dr. Goodman has received research support from Acorda Therapeutics, Biogen Idec, EMD Serono, Genzyme, Novartis, Ono, and Teva. Dr. Mayadev has nothing to disclose. Dr. Bethoux has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Merz Pharma, and Medtronic, Inc. Dr. Bethoux has received research support from Acorda Therapeutics, Innovative Neurotronics, and Medtronic Inc. Dr. Goldman has recieved personal compensation for activities with Biogen, Acorda, and Novartis. Dr. Klinger has received personal compensation for activities with Acorda Therapeutics, Inc. Dr. Klinger holds stock and/or stock options in Acorda Therapeutics, Inc. Herbert Henney is an employee of Acorda Therapeutics. Herbert Henney held stock in Acorda Therapeutics. Dr. Blight has received personal compensation for activities with Acorda Therapeutics, Inc as an employee. Dr. Blight holds stock and/or stock options in Acorda Therapeutics, Inc, which sponsored research in which Dr. Blight was involved as an investigator. Dr. Blight holds stock and/or stock optiosn in Acorda Therapeutics, Inc. Dr. Carrazana has received personal compensation for activities with Acorda Therapeutics. Dr. Carrazana holds stock and/or stock options in Acorda Therapeutics, which sponsored research in which Dr. Carrazana was involved as an investigator.