Two phase 3, multicenter, randomized, placebo-controlled clinical trials of fampridine-SR for treatment of spasticity in chronic spinal cord injury.
METHODS
Two randomized, double-blind, placebo-controlled trials.


OBJECTIVE
To evaluate the efficacy and safety of fampridine sustained-release tablets (fampridine-SR) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury (SCI).


METHODS
United States and Canada.


METHODS
Patients with incomplete chronic SCI were randomized to twice daily fampridine-SR 25 mg or placebo, with a 2-week single-blind placebo run-in, a 2-week titration, 12 weeks of stable dosing, 2 weeks of downward titration and 2 weeks of untreated follow-up. Co-primary end points were the change from baseline, averaged over the double-blind treatment period, for Ashworth score (bilateral knee flexors and extensors) and a 7-point Subject Global Impression of treatment (SGI; 1, terrible; 7, delighted). Secondary end points were: Penn Spasm Frequency Scale; the motor/sensory score from the International Standards for Neurological Classification of SCI; Clinician's Global Impression of Change of neurological status; and the International Index of Erectile Function (men) or the Female Sexual Function Index (women).


RESULTS
The populations were 212 and 203 patients in the two studies, respectively. Changes from baseline in Ashworth score were -0.15 (placebo) and -0.19 (fampridine-SR) in the first study, and -0.16 (placebo) and -0.28 (fampridine-SR) in the second study. The between-treatment difference was not significant for either the Ashworth score or the SGI and, with few exceptions, neither were the secondary end points. Fampridine-SR was generally well tolerated; treatment-emergent adverse events (TEAEs) and serious TEAEs were reported with similar frequency between treatments.


CONCLUSIONS
Fampridine-SR was well tolerated. No significant differences were observed between treatment groups for the primary end points of Ashworth score and SGI.
Department of Rehabilitation Medicine, University of Miami, Miami, FL, USA.
D D
DD
Cardenas
Department of Rehabilitation Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
J F
JF
Ditunno
Department of Rehabilitation Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA.
V
V
Graziani
Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL, USA.
A B
AB
McLain
Research Department, Craig Hospital, Englewood, CO, USA.
D P
DP
Lammertse
Department of Physical Medicine and Rehabilitation, Parkwood Hospital, St Joseph's Health Care, London, Ontario, Canada.
P J
PJ
Potter
Department of Physical Medicine and Rehabilitation, Veterans Affairs Medical Center, Birmingham, AL, USA.
M S
MS
Alexander
Acorda Therapeutics, Inc., Ardsley, NY, USA.
R
R
Cohen
Acorda Therapeutics, Inc., Ardsley, NY, USA.
A R
AR
Blight
D015761:4-Aminopyridine / Q000627:therapeutic use*; D000328:Adult; D002170:Canada; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000209:etiology; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D014481:United States
D026902:Potassium Channel Blockers; D015761:4-Aminopyridine