Prolonged-release fampridine and walking and balance in MS: randomised controlled MOBILE trial

Raymond Hupperts, Jan Lycke, Christine Short, Claudio Gasperini, Manjit McNeill, Rossella Medori, Agata Tofil-Kaluza, Maria Hovenden, Lahar R Mehta, Jacob Elkins, Raymond Hupperts, Jan Lycke, Christine Short, Claudio Gasperini, Manjit McNeill, Rossella Medori, Agata Tofil-Kaluza, Maria Hovenden, Lahar R Mehta, Jacob Elkins

Abstract

Background: Mobility impairment is a common disability in MS and negatively impacts patients' lives.

Objective: Evaluate the effect of prolonged-release (PR) fampridine (extended-release dalfampridine in the United States) on self-assessed walking disability, dynamic/static balance and safety in patients with MS.

Methods: MOBILE was a randomised, double-blind, exploratory, placebo-controlled trial. Patients with progressive/relapsing-remitting MS and Expanded Disability Status Scale score of 4.0-7.0 were treated with PR-fampridine or placebo twice daily for 24 weeks. Efficacy endpoints included change from baseline in the 12-item MS Walking Scale (MSWS-12), Timed Up and Go (TUG) test and Berg Balance Scale (BBS).

Results: 132 patients were randomised at 24 sites in six countries. PR-fampridine therapy resulted in greater median improvements from baseline in MSWS-12 score, TUG speed and BBS total score versus placebo over 24 weeks. A higher proportion of patients receiving PR-fampridine versus placebo experienced significant improvements at MSWS-12 improvement thresholds ⩾7 (p = 0.0275), ⩾8 (p = 0.0153) and ⩾9 points (p = 0.0088) and TUG speed thresholds ⩾10% (p = 0.0021) and ⩾15% (p = 0.0262). PR-fampridine was well tolerated.

Conclusions: PR-fampridine therapy resulted in early and sustained improvements in broad measures of walking and balance over six months.

Keywords: Fampridine; balance; multiple sclerosis; randomised clinical trial; walking.

Conflict of interest statement

Conflict of Interest: Dr Hupperts has received compensation for consulting, advisory boards and research grants and as a speaker for lectures from Biogen, Genzyme, Merck, Novartis and Teva.

Dr Lycke has received compensation for consulting, serving on scientific advisory boards and as a speaker for lectures from Biogen, Genzyme, Novartis and Teva.

Dr Short has received compensation for serving on scientific advisory boards and as a speaker for lectures from Biogen.

Dr Gasperini has received compensation for consulting from Bayer HealthCare and Biogen and as a speaker for lectures from Biogen, Bayer HealthCare, Genzyme, Merck Serono, Novartis and Teva.

M McNeill, Dr Tofil-Kaluza, Dr Mehta and Dr Elkins are full-time employees of Biogen.

Dr Medori was a full-time employee of Biogen at the time of this study and manuscript development.

Dr Hovenden is a full-time employee of Excel Scientific Solutions.

© The Author(s), 2015.

Figures

Figure 1.
Figure 1.
MOBILE patient disposition. AE: adverse event; CrCl: creatinine clearance; ITT: intent-to-treat; PR: prolonged-release.
Figure 2.
Figure 2.
Median changes from baseline and corresponding 95% confidence intervals in efficacy measures by study visit. Outcome measures: (a) 12-item Multiple Sclerosis Walking Scale (MSWS-12); (b) 29-item Multiple Sclerosis Impact Scale (MSIS-29) physical subscale (PHYS); (c) Timed Up and Go (TUG) test; and (d) Berg Balance Scale (BBS) were assessed at baseline (mean over screening and day 1) and weeks 2, 4, 8, 12, 16, 20, 24 and week 26 (off-treatment visit; not assessed for MSIS-29). Error bars denote non-parametric 95% confidence interval for the median change at each visit. PR: prolonged-release.
Figure 3.
Figure 3.
Cumulative percentage of patients with mean improvement in 12-item Multiple Sclerosis Walking Scale (MSWS-12) and Timed Up and Go (TUG) speed over 24 weeks. MSWS-12 (upper panel): cumulative percentage of patients with increasing levels of improvement on the MSWS-12 over the on-treatment period (weeks 2–24) across multiple thresholds (thresholds ⩽–1 to ⩽–10 represent improvements in ⩾1 to ⩾10 points). TUG speed (lower panel): cumulative percentage of patients with average percent increase from baseline in TUG speed over the on-treatment period (weeks 2–24) across multiple thresholds. PR-fampridine versus placebo: *p = 0.0275; **p = 0.0153; ***p = 0.0088; ****p = 0.0021; *****p = 0.0262. PR: prolonged-release.

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