Post-Ischemic Stroke
Conditions
Keywords
Post stroke, Ischemic stroke
Brief summary
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.
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.
Interventions
Sponsors
Acorda Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Walking Impact Scale (Walk-12) at Week 12 (Key Secondary) | Baseline, week 12 | 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) |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Placebo | 126 |
| 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.
dalfampridine-ER 7.5mg | 126 |
| 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.
dalfampridine-ER 10mg | 125 |
| Total | 377 |
Baseline characteristics
| Characteristic | Placebo | Total | Dalfampridine-ER 10mg | Dalfampridine-ER 7.5 mg |
|---|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 11.68 | 62.9 years STANDARD_DEVIATION 10.77 | 64.3 years STANDARD_DEVIATION 10.01 | 61.7 years STANDARD_DEVIATION 10.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 59 Participants | 20 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 108 Participants | 318 Participants | 105 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 6 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 9 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 51 Participants | 21 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 10 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 100 Participants | 299 Participants | 94 Participants | 105 Participants |
| Sex: Female, Male Female | 39 Participants | 136 Participants | 46 Participants | 51 Participants |
| Sex: Female, Male Male | 87 Participants | 241 Participants | 79 Participants | 75 Participants |
| Weight at Screening | 83.98 kg STANDARD_DEVIATION 14.914 | 83.63 kg STANDARD_DEVIATION 14.72 | 84.49 kg STANDARD_DEVIATION 14.771 | 82.43 kg STANDARD_DEVIATION 14.514 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 126 | 0 / 126 | 0 / 122 |
| other Total, other adverse events | 75 / 126 | 85 / 126 | 75 / 122 |
| serious Total, serious adverse events | 8 / 126 | 6 / 126 | 3 / 122 |
Outcome results
Primary
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.
Time frame: Week 12
Population: Includes all randomized subjects who took at least one dose of double-blind study treatment, had at least one 2MinWT assessment during the placebo run-in period, and at least one 2MinWT assessment during the double-blind treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Responder | 17 participants |
| Placebo | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Missing | 12 participants |
| Placebo | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Non-Responder | 97 participants |
| Dalfampridine-ER 7.5 mg | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Missing | 8 participants |
| Dalfampridine-ER 7.5 mg | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Non-Responder | 96 participants |
| Dalfampridine-ER 7.5 mg | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Responder | 17 participants |
| Dalfampridine-ER 10mg | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Non-Responder | 90 participants |
| Dalfampridine-ER 10mg | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Missing | 8 participants |
| Dalfampridine-ER 10mg | Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | Responder | 23 participants |
Secondary
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)
Time frame: Baseline, week 12
Population: Includes all randomized subjects who took at least one dose of double-blind study treatment, had at least one 2MinWT assessment during the placebo run-in period, and at least one 2MinWT assessment during the double-blind treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the Walking Impact Scale (Walk-12) at Week 12 (Key Secondary) | 45.40 units on a scale | Standard Deviation 22.96 |
| Dalfampridine-ER 7.5 mg | Change From Baseline on the Walking Impact Scale (Walk-12) at Week 12 (Key Secondary) | 48.34 units on a scale | Standard Deviation 25.43 |
| Dalfampridine-ER 10mg | Change From Baseline on the Walking Impact Scale (Walk-12) at Week 12 (Key Secondary) | 49.26 units on a scale | Standard Deviation 25.98 |