Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multip...

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Published in:	Multiple sclerosis Vol. 21; no. 10; pp. 1322 - 1331
Main Authors:	Goodman, Andrew D, Bethoux, Francois, Brown, Theodore R, Schapiro, Randall T, Cohen, Ron, Marinucci, Lawrence N, Henney, Herbert R, Blight, Andrew R, Agius, M, Arnason, BGW, Bethoux, FA, Bever, CT, Bowen, JD, Brown, TR, Dietrich, DW, Edwards, K, Freedman, MS, Freedman, M, Kachuck, NJ, Kaufman, MD, Keilson, M, Khan, O, Krupp, LB, Leist, TP, Lindsey, JW, Lublin, FD, Mass, MK, Mattson, D, McGowan, D, Naismith, R, O’Connell, C, Oger, JJ, Panitch, H, Picone, MA, Rammohan, KW, Schapiro, RT, Schwid, SR, Scott, T, Short, C, Thrower, BW, Vollmer, TL, Camac, A, Cooper, JA, Chumley, WF, Cross, A, Dunnigan, RT, Gitt, JS, Hillen, M, Jeffrey, DR, Khatri, BO, Kresa-Reahl, K, Moon, S, Preiningerova, J, Tullman, M, Weinstock-Guttman, B, Wynn, DR
Format:	Journal Article
Language:	English
Published:	London, England SAGE Publications 01-09-2015 Sage Publications Ltd
Subjects:	4-Aminopyridine - administration & dosage 4-Aminopyridine - therapeutic use Adult Aged Double-Blind Method Europe Female Humans Male Middle Aged Multiple Sclerosis - drug therapy Original Research Papers Potassium Channel Blockers - therapeutic use Treatment Outcome Walking - physiology Europe dalfampridine Timed 25-Foot Walk long-term effects sustained release multiple sclerosis safety tolerability Clinical trial efficacy walking speed
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Summary:	Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	1352-4585 1477-0970
DOI:	10.1177/1352458514563591