Ischemic Stroke
Conditions
Brief summary
This is a multi-center, safety and tolerability study in subjects with chronic stable sensorimotor deficits after ischemic stroke. It has been designed as a double-blind, placebo-controlled, 2-period crossover study.
Interventions
DRUGplacebo/dalfampridine-ER
Sequence A: placebo in Period 1 and dalfampridine-ER in Period 2. 10mg tablets, will be taken orally, twice daily approximately 12 hours apart
DRUGdalfampridine-ER/placebo
Sequence B: dalfampridine-ER in Period 1 and placebo in Period 2. 10mg tablets, will be taken orally, twice daily approximately 12 hours apart
Sponsors
Acorda Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* History of a stable sensorimotor deficit due to an ischemic stroke, as confirmed by the Investigator with supportive prior imaging findings (MRI/ CT scan) * ≥ 6 months post-stroke * Have a body mass index (BMI) ranging between 18.0 - 35.0 kg/m,2 inclusive * Stable concomitant medication therapy regimen within 4 weeks of screening visit
Exclusion criteria
* 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 * Botulinum toxin use within 2 months prior to the Screening Visit * Orthopedic surgical procedures in any of the extremities within the past 6 months * Diagnosis of multiple sclerosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | up to 36 days | A TEAE is defined as any adverse event with date of onset (or worsening) on or after the start-date of double-blind treatment through 7 days after the last dose of double-blind treatment. The severity categories of mild, moderate or severe, are defined below: * Mild is defined as causing no limitation of usual activities * Moderate is defined as causing some limitation of usual activities * Severe is defined as causing inability to carry out usual activities |
Other
| Measure | Time frame |
|---|---|
| Walking Speed Measured by the Timed 25 Foot Walk Test (T25FW) | Screening visit, Days 1, 8, 15, 22, 29 and 36 |
| Motor and Sensory Function as Measured by the Fugl-Meyer Assessment (FMA) | Screening visit, Days 1, 8, 15, 22, 29, and 36 |
| Manual Dexterity as Measured by the Box and Block Test | Days 1, 8, 15, 22, 29, and 36 |
| Assistance Required to Perform Activities of Daily Living (ADL) by the Functional Independence Measure (FIM) Scale | Days 1, 8, 15, 22, 29, and 36 |
| Subject Global Impression (SGI) Scale | Days 8, 15, 22, 29 and 36 |
| Clinician Global Impression (CGI) Scale | Days 8, 15, 22, 29 and 36 |
| Hand Strength as Measured by the Grip Test and Pinch Tests | Days 1, 8, 15, 22, 29, and 36 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Dalfampridine-ER Subjects will be randomized at day 1 to one of two blinded treatment sequences (A or B) in a 2:1 ratio respectively, according to a randomization created prior to the start of the study:
Period 1 = days 1, 8 and 15. Period 2 = Days 22, 29, and 36
dalfampridine-ER: Sequence A: placebo in Period 1 and dalfampridine-ER in Period 2.
10mg tablets, will be taken orally, twice daily approximately 12 hours apart | 55 |
| Dalfampridine-ER/Placebo Subjects will be randomized at day 1 to one of two blinded treatment sequences (A or B) in a 2:1 ratio respectively, according to a randomization created prior to the start of the study:
Period 1 = days 1, 8 and 15. Period 2 = Days 22, 29, and 36
dalfampridine-ER: Sequence B: dalfampridine-ER in Period 1 and placebo in Period 2.
10mg tablets, will be taken orally, twice daily approximately 12 hours apart | 28 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Non-Compliance -Investigational Drug | 3 | 0 |
| Overall Study | Non-Compliance with Protocol | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo/Dalfampridine-ER | Dalfampridine-ER/Placebo | Total |
|---|---|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 9.72 | 63.5 years STANDARD_DEVIATION 8.91 | 59.5 years STANDARD_DEVIATION 9.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 4 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 38 Participants | 22 Participants | 60 Participants |
| Sex: Female, Male Female | 18 Participants | 10 Participants | 28 Participants |
| Sex: Female, Male Male | 37 Participants | 18 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 81 | 42 / 77 |
| serious Total, serious adverse events | 2 / 81 | 2 / 77 |
Outcome results
Primary
Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as any adverse event with date of onset (or worsening) on or after the start-date of double-blind treatment through 7 days after the last dose of double-blind treatment. The severity categories of mild, moderate or severe, are defined below: * Mild is defined as causing no limitation of usual activities * Moderate is defined as causing some limitation of usual activities * Severe is defined as causing inability to carry out usual activities
Time frame: up to 36 days
Population: Safety population. Number of participants analyzed is number of patients with TEAE's as described in outcome measure description. Excludes pre-treatment and post-treatment adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | Subjects with any TEAEs | 30 participants |
| Placebo | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Possibly Related to study drug | 16 participants |
| Placebo | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Maximum Severity - Mild | 16 participants |
| Placebo | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Maximum Severity - Moderate | 13 participants |
| Placebo | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Maximum Severity - Severe | 1 participants |
| Placebo | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to withdrawal of study drug | 1 participants |
| Placebo | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Serious | 2 participants |
| Placebo | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | Subjects who died | 0 participants |
| Dalfampridine-ER | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | Subjects who died | 0 participants |
| Dalfampridine-ER | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | Subjects with any TEAEs | 42 participants |
| Dalfampridine-ER | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Maximum Severity - Severe | 3 participants |
| Dalfampridine-ER | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Possibly Related to study drug | 24 participants |
| Dalfampridine-ER | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Serious | 2 participants |
| Dalfampridine-ER | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Maximum Severity - Mild | 29 participants |
| Dalfampridine-ER | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to withdrawal of study drug | 5 participants |
| Dalfampridine-ER | Safety and Tolerability of Dalfampridine-ER in Subjects With Chronic Deficits After Ischemic Stroke Assessed by Number of Treatment Emergent Adverse Events (TEAEs) | TEAEs Maximum Severity - Moderate | 10 participants |
Other Pre-specified
Assistance Required to Perform Activities of Daily Living (ADL) by the Functional Independence Measure (FIM) Scale
Time frame: Days 1, 8, 15, 22, 29, and 36
Other Pre-specified
Clinician Global Impression (CGI) Scale
Time frame: Days 8, 15, 22, 29 and 36
Other Pre-specified
Hand Strength as Measured by the Grip Test and Pinch Tests
Time frame: Days 1, 8, 15, 22, 29, and 36
Other Pre-specified
Manual Dexterity as Measured by the Box and Block Test
Time frame: Days 1, 8, 15, 22, 29, and 36
Other Pre-specified
Motor and Sensory Function as Measured by the Fugl-Meyer Assessment (FMA)
Time frame: Screening visit, Days 1, 8, 15, 22, 29, and 36
Other Pre-specified
Subject Global Impression (SGI) Scale
Time frame: Days 8, 15, 22, 29 and 36
Other Pre-specified
Walking Speed Measured by the Timed 25 Foot Walk Test (T25FW)
Time frame: Screening visit, Days 1, 8, 15, 22, 29 and 36