A Study to Evaluate the Efficacy and Safety of Two Dose Strengths of Dalfampridine Extended Release Tablets. (MILESTONE℠)

This is a Multi-center, Double-blind, Three Arm, Parallel Group, Placebo-controlled, Randomized Study Designed to Evaluate the Efficacy, Safety and Tolerability of Dalfampridine.

The objective of this study is to determine the effect of two dose strengths of dalfampridine-Extended Release (ER) tablets, taken twice daily for 12 weeks, on stable walking deficits in subjects with post-ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Post-Ischemic Stroke
• Intervention / Treatment: Drug: Placebo; Drug: dalfampridine-ER 7.5mg; Drug: dalfampridine-ER 10mg

Detailed Description

This was a randomized, placebo-controlled, three-arm, parallel-group study designed to evaluate the efficacy, safety, and tolerability of dalfampridine extended release (ER) tablets on chronic walking deficits in subjects with post-ischemic stroke.

• Study Type: Interventional
• Enrollment (Actual): 377
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B0C7
      • Acorda Site #203
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H4K4
      • Acorda Site #202
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V2G9
      • Acorda Site #201
    • Montréal, Quebec, Canada, H3G1A4
      • Acorda Site #204
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Acorda Site #117
  • California
    • Berkeley, California, United States, 94705
      • Acorda Site #109
    • Long Beach, California, United States, 90806
      • Acorda Site #138
    • Newport Beach, California, United States, 92663
      • Acorda Site #105
    • Oceanside, California, United States, 92056
      • Acorda Site #170
    • Pasadena, California, United States, 91105
      • Acorda Site #142
    • Sacramento, California, United States, 95823
      • Acorda Site #153
    • San Diego, California, United States, 92103
      • Acorda Site #151
    • San Diego, California, United States, 92123
      • Acorda Site #163
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Acorda Site #124
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Acorda Site #110
    • Fairfield, Connecticut, United States, 06824
      • Acorda Site #149
    • Stamford, Connecticut, United States, 06905
      • Acorda Site #130
  • Florida
    • Atlantis, Florida, United States, 33462
      • Acorda Site #115
    • Deerfield Beach, Florida, United States, 33064
      • Acorda Site #119
    • Gainesville, Florida, United States, 32611
      • Acorda Site #147
    • Hialeah, Florida, United States, 33012
      • Acorda Site #128
    • Jacksonville, Florida, United States, 32209
      • Acorda Site #143
    • Miami, Florida, United States, 33142
      • Acorda Site #103
    • Miami, Florida, United States, 33175
      • Acorda Site #133
    • Naples, Florida, United States, 34102
      • Acorda Site #161
    • Sunrise, Florida, United States, 33351
      • Acorda Site #145
    • Tampa, Florida, United States, 33606
      • Acorda Site #106
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Acorda Site #186
  • Hawaii
    • Kailua, Hawaii, United States, 96734
      • Acorda Site #181
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Acorda Site #171
  • Indiana
    • Avon, Indiana, United States, 46123
      • Acorda Site #148
    • Fort Wayne, Indiana, United States, 46805
      • Acorda Site #188
    • Franklin, Indiana, United States, 46131
      • Acorda Site #156
  • Kentucky
    • Lexington, Kentucky, United States, 40513
      • Acorda Site #146
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Acorda Site #150
  • Maryland
    • Fulton, Maryland, United States, 20759
      • Acorda Site #175
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Acorda Site #136
    • Boston, Massachusetts, United States, 02118
      • Acorda Site #121
    • Worcester, Massachusetts, United States, 016052610
      • Acorda Site #120
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Acorda Site #164
    • Detroit, Michigan, United States, 48201
      • Acorda Site #127
    • East Lansing, Michigan, United States, 48824
      • Acorda Site #123
    • Grand Rapids, Michigan, United States, 49503
      • Acorda Site #159
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Acorda Site #101
  • Montana
    • Great Falls, Montana, United States, 59405
      • Acorda Site #111
  • Nevada
    • Reno, Nevada, United States, 89502
      • Acorda Site #140
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Acorda Site #131
    • Stratford, New Jersey, United States, 08084
      • Acorda Site #177
  • New York
    • New York, New York, United States, 10029
      • Acorda Site #172
    • New York, New York, United States, 11220
      • Acorda Site #102
    • Patchogue, New York, United States, 11772
      • Acorda Site #179
    • White Plains, New York, United States, 10605
      • Acorda Site #114
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Acorda Site #166
    • Durham, North Carolina, United States, 27705
      • Acorda Site #167
    • Mooresville, North Carolina, United States, 28117
      • Acorda Site #162
    • Raleigh, North Carolina, United States, 276076010
      • Acorda Site #154
    • Winston-Salem, North Carolina, United States, 27103
      • Acorda Site #132
  • Ohio
    • Bellevue, Ohio, United States, 44811
      • Acorda Site #187
    • Cleveland, Ohio, United States, 44195
      • Acorda Site #160
    • Columbus, Ohio, United States, 43210
      • Acorda Site #137
    • Dayton, Ohio, United States, 45417
      • Acorda Site #116
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • Acorda Site #152
    • Portland, Oregon, United States, 97225
      • Acorda Site #168
    • Portland, Oregon, United States, 97239
      • Acorda Site #126
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Acorda Site #158
    • Philadelphia, Pennsylvania, United States, 19104
      • Acorda Site #122
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Acorda Site #144
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • Acorda Site #157
  • Texas
    • Dallas, Texas, United States, 75214
      • Acorda Site #113
    • Dallas, Texas, United States, 75246
      • Acorda Site #165
    • Houston, Texas, United States, 77030
      • Acorda Site #108
  • Virginia
    • Alexandria, Virginia, United States, 22310
      • Acorda Site #182
    • Richmond, Virginia, United States, 23298
      • Acorda Site #176
  • Washington
    • Spokane, Washington, United States, 992021330
      • Acorda Site #107

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical evidence of a stable walking deficit due to an ischemic stroke, as judged by the Investigator, based on review of medical records and physical exam. Such deficit was not present prior to the stroke and cannot be attributed primarily to other conditions (e.g. chronic obstructive pulmonary disease, arthritis). Evidence of walking deficits is objectively supported by any one of the following findings on clinical examination:

  1. obvious slowness of movement assigned primarily to the stroke
  2. use of an assistive walking device such as a cane or walker
  3. Presence of movement pattern deviations such as stiff-legged gait, foot drop, hip hiking and hip circumduction
• Modified Rankin Scale score of 1 - 3, regardless of the cause(s) of the disability
• Sufficient ambulatory ability to independently complete the 2MinWT and 10MWT
• ≥ 6 months from occurrence of most recent stroke

Exclusion Criteria:

• Woman who is not surgically sterile or is less than 2 years postmenopausal, and does not agree to use a highly effective birth control method during the study and up to 3 months after the last dose of investigational product.
• Woman who is pregnant, breastfeeding, or planning to become pregnant
• History of seizures, except simple febrile seizures
• Moderate or severe renal impairment as defined by a calculated creatinine clearance of ≤ 50 mL/minute using the Cockcroft-Gault Equation
• Suicide attempt within 1 year prior to the Screening Visit, or severe suicidal ideation within 6 months prior to the Screening Visit, or subject is at significant risk of suicidal behavior in the opinion of the Investigator
• Previous use of AMPYRA, dalfampridine, fampridine or 4-aminopyridine (4-AP)
• Initiation of a serotonin reuptake inhibitor (SSRI) within 3 months prior to the Screening Visit, or any change in dosing regimen within 3 months prior to the Screening Visit
• Botulinum toxin use within 2 months prior to the Screening Visit
• Orthopedic surgical procedures in any of the extremities within the past 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects randomized 1:1:1 to receive either dalfampridine-ER 7.5mg, dalfampridine-ER 10mg, or matching placebo tablets taken twice daily 12 hours apart.	Drug: Placebo
Active Comparator: dalfampridine-ER 7.5 mg; Subjects randomized 1:1:1 to receive either dalfampridine-ER 7.5mg, dalfampridine-ER 10mg, or matching placebo tablets taken twice daily 12 hours apart.	Drug: dalfampridine-ER 7.5mg
Active Comparator: dalfampridine-ER 10mg; Subjects randomized 1:1:1 to receive either dalfampridine-ER 7.5mg, dalfampridine-ER 10mg, or matching placebo tablets taken twice daily 12 hours apart.	Drug: dalfampridine-ER 10mg; Other Names: Ampyra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12	"The 2MinWT measures the distance a subject can walk in 2 minutes. Participants showing at Least a 20% Improvement on the 2MinWT at 12-weeks are considered "Responders".	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline on the Walking Impact Scale (Walk-12) at Week 12 (Key Secondary)	The Walk-12 is a 12-question questionnaire that asks subjects to rate limitations of their mobility during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). For each visit, the Walk-12 score will be calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. A higher score indicates a greater degree of limitation in walking. A negative change indicates an improvement in walking. 0 = no limitation in mobility to 100 extreme limitation in mobility. Walk-12 Score = 100 * [(Mean of the 12 items) - 1]/(5-1)	Baseline, week 12

Collaborators and Investigators

• Sponsor: Acorda Therapeutics

Publications and helpful links

General Publications

• Page SJ, Kasner SE, Bockbrader M, Goldstein M, Finklestein SP, Ning M, El-Feky WH, Wilson CA, Roberts H; all of the investigators involved in the MILESTONE study. A double-blind, randomized, controlled study of two dose strengths of dalfampridine extended release on walking deficits in ischemic stroke. Restor Neurol Neurosci. 2020;38(4):301-309. doi: 10.3233/RNN-201009.

Helpful Links

• Click here for potential enrollment or for more information about this study: DALF-PS-1016

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: October 20, 2014
• First Submitted That Met QC Criteria: October 21, 2014
• First Posted (Estimate): October 22, 2014

Study Record Updates

• Last Update Posted (Actual): June 7, 2018
• Last Update Submitted That Met QC Criteria: June 4, 2018
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Ischemic stroke; Post stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: DALF-PS-1016