title: Evaluation of Dalfampridine Extended Release 5 and 10 mg in Multiple Sclerosis: A Randomized Controlled Trial.
abstract: BACKGROUND
  Dalfampridine extended-release (ER) tablets, 10 mg twice daily, have been shown to improve walking in people with multiple sclerosis. We evaluated the safety and efficacy of dalfampridine-ER 5 mg compared with 10 mg.
  
  
  METHODS
  Patients were randomized to double-blind treatment with twice-daily dalfampridine-ER tablets, 5 mg (n = 144) or 10 mg (n = 143), or placebo (n = 143) for 4 weeks. Primary efficacy endpoint was change from baseline walking speed by the Timed 25-Foot Walk 3 to 4 hours after the last dose. At 40% of sites, 2-week change from baseline walking distance was measured by the 6-Minute Walk test.
  
  
  RESULTS
  At 4 weeks, walking speed changes from baseline were 0.363, 0.423, and 0.478 ft/s (placebo, dalfampridine-ER 5 mg, and dalfampridine-ER 10 mg, respectively [P = NS]). Post hoc analysis of average changes between pretreatment and on-treatment showed that relative to placebo, only dalfampridine-ER 10 mg demonstrated a significant increase in walking speed (mean ± SE): 0.443 ± 0.042 ft/s versus 0.303 ± 0.038 ft/s (P = .014). Improvement in 6-Minute Walk distance was significantly greater with dalfampridine-ER 10 mg (128.6 ft, P = .014) but not with 5 mg (76.8 ft, P = .308) relative to placebo (41.7 ft). Adverse events were consistent with previous studies. No seizures were reported.
  
  
  CONCLUSIONS
  Dalfampridine-ER 5 and 10 mg twice daily did not demonstrate efficacy on the planned endpoint. Post hoc analyses demonstrated significant increases in walking speed relative to placebo with dalfampridine-ER 10 mg. No new safety signals were observed.
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Robert
authors.initials: R
authors.lastname: Yapundich
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Angela
authors.initials: A
authors.lastname: Applebee
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Francois
authors.initials: F
authors.lastname: Bethoux
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Myla D
authors.initials: MD
authors.lastname: Goldman
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: George J
authors.initials: GJ
authors.lastname: Hutton
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Michele
authors.initials: M
authors.lastname: Mass
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Gabriel
authors.initials: G
authors.lastname: Pardo
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Michael
authors.initials: M
authors.lastname: Klingler
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Herbert R
authors.initials: HR
authors.lastname: Henney
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Blight
authors.affiliation: PMG Research of Hickory, Hickory, NC, USA (RY); Fletcher Allen Health Care, Burlington, VT, USA (AA); Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic, Cleveland, OH, USA (FB); Department of Neurology, University of Virginia, Charlottesville, VA, USA (MDG); Department of Neurology, Baylor College of Medicine, Houston, TX, USA (GJH); Oregon Health and Science University, Portland, OR, USA (MM); Oklahoma Medical Research Foundation Multiple Sclerosis Center of Excellence, Oklahoma City, OK, USA (GP); and Acorda Therapeutics Inc, Ardsley, NY, USA (MK, HRH, ARB, EJC).
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Carrazana