A Pooled Analysis of Two Phase 3 Clinical Trials of Dalfampridine in Patients with Multiple Sclerosis

Goodman, Andrew; Brown, Theodore R.; Schapiro, Randall T.; Klingler, Michael; Cohen, Ron; Blight, Andrew R.

doi:10.7224/1537-2073.2013-023

Cited by 26 publications

(47 citation statements)

References 30 publications

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“…Two phase III trials showed that oral administration of prolonged-release fampridine (PRfampridine; dalfampridine) increases walking speed in the timed 25-foot walk test (T25FW) in a subset of patients with MS (timed-walk responders) [6][7][8] . The active substance 4-aminopyridine (4-AP) leads to improved signal conduction in demyelinated axons via the blockade of voltage-gated potassium channels 9 .…”

Section: Introductionmentioning

confidence: 99%

Prolonged-release fampridine in multiple sclerosis: Improved ambulation effected by changes in walking pattern

et al. 2016

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BACKGROUND Prolonged-release fampridine (PR-fampridine, 4-aminopyridine) increases walking speed in the timed 25-foot walk test (T25FW) in some patients (timed-walk responders) with multiple sclerosis (MS). OBJECTIVE To explore the effects of PR-fampridine on different aspects of walking function and to identify associated gait modifications in subjects with MS. METHODS In this prospective, randomized, placebo-controlled, double-blind, phase II study (FAMPKIN; clinicaltrials.gov, NCT01576354), subjects received a 6-week course of oral placebo or PR-fampridine treatment (10 mg, twice daily) before crossing over. Using 3D-motion-analysis, kinematic and kinetic parameters were assessed during treadmill walking (primary endpoint). Clinical outcome measures included T25FW, 6-minute walk test (6MWT), and balance scales. Physical activity in everyday life was measured with an accelerometer device. RESULTS Data from 55 patients were suitable for analysis. Seventeen subjects were timed-walk responders under PR-fampridine. For the total study population and for responders, a significant increase in walking speed (T25FW) and distance (6MWT) was observed. Gait pattern changes were found at the single-subject level and correlated with improvements in the T25FW and 6MWT. Physical activity was increased in responders. CONCLUSION PR-fampridine improves walking speed, endurance, and everyday physical activity in a subset of subjects with MS and leads to individual modifications of the gait pattern.

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Section: Introductionmentioning

confidence: 99%

Prolonged-release fampridine in multiple sclerosis: Improved ambulation effected by changes in walking pattern

et al. 2016

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“…3 We showed that providing a progressive, multicomponent PT program customized to continuously challenge the individual's ability in balance, gait, strength, and coordination, concurrently with prescribed D-ER, helped this participant make adjustments to her gait pattern. Treadmill speed and duration of walking bouts were adjusted according to her individual ability and fatigue, but speed, endurance, and independence (reduced manual assistance and verbal cueing from the therapist and reduced reliance on handrails for reactive postural adjustments) were progressed in each session.…”

Section: Discussionmentioning

confidence: 88%

“…Manual assistance was provided as needed (eg, to facilitate increased step length); however, she was responsive to verbal cueing to four on-treatment visits compared with the maximum off-drug T25FW gait speed. 3 Responders average 25% improvement in T25FW gait speed, whereas the average change in nonresponders is only 7%. 3 Exercise and gait training interventions may be an excellent alternative or adjunct treatment for patients who do not respond meaningfully to D-ER alone.…”

Section: Interventionsmentioning

confidence: 91%

“…3 Responders average 25% improvement in T25FW gait speed, whereas the average change in nonresponders is only 7%. 3 Exercise and gait training interventions may be an excellent alternative or adjunct treatment for patients who do not respond meaningfully to D-ER alone. Two meta-analyses 5,6 and three systematic reviews [7][8][9] provide evidence that both exercise and task-specific gait training interventions can improve walking ability in people with MS.…”

Section: Interventionsmentioning

confidence: 91%

“…1,2 Unfortunately, pooled results from two phase 3 clinical trials demonstrated that a clinically meaningful improvement is observed in only 33% of all people who take D-ER. 3 A clinically meaningful improvement is defined by at least 20% improvement in gait speed on the Timed 25-Foot Walk (T25FW) test. 4 The "responder" rate is slightly higher (38%) when responders are defined as patients with faster walking speed for at least three of the…”

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confidence: 99%

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