A phase 3 trial of extended release oral dalfampridine in multiple sclerosis.
Author(s): Goodman AD, Brown TR, Edwards KR, Krupp LB, Schapiro RT, Cohen R, Marinucci LN,
Blight AR; MSF204 Investigators.
Collaborators: Agius M, Arnason BG, Bethoux FA, Bever CT Jr, Brown TR, Camac A,
Cooper JA, Chumley WF, Cross A, Dietrich DW, Dunnigan RT, Edwards K, Freedman M,
Gitt JS, Hillen M, Jeffery DR, Kachuck NJ, Khatri BO, Kaufman MD, Khan O,
Kresa-Reahl K, Krupp LB, Leist TP, Lublin FD, Mass MK, Mattson D, McGowan D, Moon
S, O'Connell C, Oger JJ, Panitch H, Picone MA, Preiningerova J, Rammohan KW,
Schapiro RT, Schwid SR, Short C, Thrower BW, Tullman M, Weinstock-Guttman B, Wynn
DR, Vollmer TL.
Affiliation(s): Department of Neurology, University of Rochester Medical Center, Rochester, NY
14642, USA. andrew_goodman@urmc.rochester.edu
Publication date & source: 2010, Ann Neurol. , 68(4):494-502
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.
|