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

Acorda Therapeutics

Status and phase: Completed; Phase 3

Conditions: Post-Ischemic Stroke

Treatments: Drug: Placebo; Drug: dalfampridine-ER 7.5mg; Drug: dalfampridine-ER 10mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02271217

DALF-PS-1016

Details and patient eligibility

About

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.

Full 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.

Enrollment: 377 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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377 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

dalfampridine-ER 7.5 mg

Active Comparator group

Description:

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.

Treatment:

Drug: dalfampridine-ER 7.5mg

dalfampridine-ER 10mg

Active Comparator group

Description:

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.

Treatment:

Drug: dalfampridine-ER 10mg