Muscle Spasticity, Stroke
Conditions
Brief summary
This is a safety and efficacy study of onabotulinumtoxinA in poststroke patients with upper limb spasticity.
Interventions
BIOLOGICALonabotulinumtoxinA
OnabotulinumtoxinA injected into predefined muscles of the study limb on Day 1.
DRUGplacebo (normal saline)
Placebo (normal saline) injected into predefined muscles of the study limb on Day 1.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Upper limb spasticity in the elbow and shoulder due to stroke, with the most recent stroke at least 3 months ago
Exclusion criteria
* Spasticity in the non-study upper limb that requires treatment * Presence of fixed contractures in of the study muscles in elbow or shoulder * Profound atrophy of muscles to be injected * Previous surgical intervention, nerve block, or muscle block for the treatment of spasticity in the study limb in the last 12 months * Injection of corticosteroids or anesthetics, use of casting or dynamic splinting or constraint-induced movement therapy (CIMT) for the study limb within 3 months * Ultrasound therapy, electrical stimulation, or acupuncture in the study limb within 1 month * Condition other than stroke contributing to upper limb spasticity * Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, and/or amyotrophic lateral sclerosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Modified Ashworth Scale-Bohannon (MAS-B) Score of Elbow Flexors Using a 6-Point Scale | Baseline, Week 6 | The MAS-B is a 6-point scale used to evaluate spasticity based on grading the resistance encountered in the elbow flexors by passively moving the elbow flexor muscles through their range of motion. The score ranges from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). Scores are converted to a 0 to 5 grade. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the MAS-B Score of Shoulder Adductors Using a 6-Point Scale | Baseline, Week 6 | The MAS-B is a 6-point scale used to evaluate spasticity based on grading the resistance encountered in the shoulder adductors by passively moving the shoulder adductor muscles through their range of motion. The score ranges from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). Scores are converted to a 0 to 5 grade. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. |
| Change From Baseline in Pain on an 11-Point Scale | Baseline, Week 6 | The patient is asked to select a number that best describes his/her pain in the treated areas of the study limb on an 11-point scale from 0 = no pain to 10 = pain as bad as can be imagined. Patients are instructed to recall their average pain in the study limb during the 48-hour period prior to the visit. Patients with a baseline pain score \>0 are included in the analyses. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. |
| Change From Baseline in the Dressing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline, Week 6 | The SIA-UL asks the patient to assess the impact of upper limb spasticity in his/her daily life on a 19-item scale. The scale covers impacts on activities of dressing, showering/bathing, and self-care. The SIA score ranged from 0 (not at all difficult) to 4 (extremely difficult) for each question. The dressing domain was calculated based on the average of 2 questions. |
| Change From Baseline in the Showering/Bathing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline, Week 6 | The SIA-UL asks the patient to assess the impact of upper limb spasticity his/her daily life on a 19-item scale. The scale covers impacts on activities of dressing, showering/bathing, and self-care. The SIA score ranged from 0 (not at all difficult) to 4 (extremely difficult) for each question. The showering/bathing domain was based on a single question. |
| Change From Baseline in the Self-Care Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline, Week 6 | The SIA-UL asks the patient to assess the impact of upper limb spasticity in his/her daily life on a 19-item scale. The scale covers impacts on activities of dressing, showering/bathing, and self-care. The SIA score ranged from 0 (not at all difficult) to 4 (extremely difficult) for each question. The self-care domain was calculated based on the average of 4 questions. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| onabotulinumtoxinA 500U OnabotulinumtoxinA 500U injected into predefined muscles of the study limb on Day 1. | 17 |
| onabotulinumtoxinA 300U OnabotulinumtoxinA 300U injected into predefined muscles of the study limb on Day 1. | 18 |
| Placebo (Normal Saline) Placebo (normal saline) injected into predefined muscles of the study limb on Day 1. | 18 |
| Total | 53 |
Baseline characteristics
| Characteristic | onabotulinumtoxinA 500U | onabotulinumtoxinA 300U | Placebo (Normal Saline) | Total |
|---|---|---|---|---|
| Age, Continuous | 58.8 Years STANDARD_DEVIATION 11.46 | 59.7 Years STANDARD_DEVIATION 10.36 | 56.2 Years STANDARD_DEVIATION 8.3 | 58.2 Years STANDARD_DEVIATION 10.01 |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 8 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 17 | 5 / 18 | 7 / 18 |
| serious Total, serious adverse events | 2 / 17 | 0 / 18 | 3 / 18 |
Outcome results
Primary
Change From Baseline in the Modified Ashworth Scale-Bohannon (MAS-B) Score of Elbow Flexors Using a 6-Point Scale
The MAS-B is a 6-point scale used to evaluate spasticity based on grading the resistance encountered in the elbow flexors by passively moving the elbow flexor muscles through their range of motion. The score ranges from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). Scores are converted to a 0 to 5 grade. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.
Time frame: Baseline, Week 6
Population: Intent-to-Treat: all randomized patients who were analyzed according to randomization assignment, regardless of treatment actually received
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| onabotulinumtoxinA 500U | Change From Baseline in the Modified Ashworth Scale-Bohannon (MAS-B) Score of Elbow Flexors Using a 6-Point Scale | Baseline | 4.12 Scores on a Scale | Standard Deviation 0.332 |
| onabotulinumtoxinA 500U | Change From Baseline in the Modified Ashworth Scale-Bohannon (MAS-B) Score of Elbow Flexors Using a 6-Point Scale | Change from Baseline at Week 6 | -1.62 Scores on a Scale | Standard Deviation 1.455 |
| onabotulinumtoxinA 300U | Change From Baseline in the Modified Ashworth Scale-Bohannon (MAS-B) Score of Elbow Flexors Using a 6-Point Scale | Baseline | 4.06 Scores on a Scale | Standard Deviation 0.236 |
| onabotulinumtoxinA 300U | Change From Baseline in the Modified Ashworth Scale-Bohannon (MAS-B) Score of Elbow Flexors Using a 6-Point Scale | Change from Baseline at Week 6 | -1.47 Scores on a Scale | Standard Deviation 1.247 |
| Placebo (Normal Saline) | Change From Baseline in the Modified Ashworth Scale-Bohannon (MAS-B) Score of Elbow Flexors Using a 6-Point Scale | Baseline | 4.17 Scores on a Scale | Standard Deviation 0.383 |
| Placebo (Normal Saline) | Change From Baseline in the Modified Ashworth Scale-Bohannon (MAS-B) Score of Elbow Flexors Using a 6-Point Scale | Change from Baseline at Week 6 | -0.74 Scores on a Scale | Standard Deviation 0.97 |
Secondary
Change From Baseline in Pain on an 11-Point Scale
The patient is asked to select a number that best describes his/her pain in the treated areas of the study limb on an 11-point scale from 0 = no pain to 10 = pain as bad as can be imagined. Patients are instructed to recall their average pain in the study limb during the 48-hour period prior to the visit. Patients with a baseline pain score \>0 are included in the analyses. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.
Time frame: Baseline, Week 6
Population: Intent-to-Treat: all randomized patients who were analyzed according to randomization assignment, regardless of treatment actually received
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| onabotulinumtoxinA 500U | Change From Baseline in Pain on an 11-Point Scale | Baseline | 4.89 Scores on a Scale | Standard Deviation 2.714 |
| onabotulinumtoxinA 500U | Change From Baseline in Pain on an 11-Point Scale | Change from Baseline at Week 6 | -2.08 Scores on a Scale | Standard Deviation 3.585 |
| onabotulinumtoxinA 300U | Change From Baseline in Pain on an 11-Point Scale | Baseline | 6.05 Scores on a Scale | Standard Deviation 3.197 |
| onabotulinumtoxinA 300U | Change From Baseline in Pain on an 11-Point Scale | Change from Baseline at Week 6 | -2.51 Scores on a Scale | Standard Deviation 4.606 |
| Placebo (Normal Saline) | Change From Baseline in Pain on an 11-Point Scale | Baseline | 5.13 Scores on a Scale | Standard Deviation 3.586 |
| Placebo (Normal Saline) | Change From Baseline in Pain on an 11-Point Scale | Change from Baseline at Week 6 | -2.64 Scores on a Scale | Standard Deviation 3.857 |
Secondary
Change From Baseline in the Dressing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL)
The SIA-UL asks the patient to assess the impact of upper limb spasticity in his/her daily life on a 19-item scale. The scale covers impacts on activities of dressing, showering/bathing, and self-care. The SIA score ranged from 0 (not at all difficult) to 4 (extremely difficult) for each question. The dressing domain was calculated based on the average of 2 questions.
Time frame: Baseline, Week 6
Population: Intent-to-Treat: all randomized patients who were analyzed according to randomization assignment, regardless of treatment actually received
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| onabotulinumtoxinA 500U | Change From Baseline in the Dressing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.61 Scores on a Scale | Standard Deviation 1.346 |
| onabotulinumtoxinA 500U | Change From Baseline in the Dressing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.36 Scores on a Scale | Standard Deviation 0.854 |
| onabotulinumtoxinA 300U | Change From Baseline in the Dressing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.91 Scores on a Scale | Standard Deviation 1.123 |
| onabotulinumtoxinA 300U | Change From Baseline in the Dressing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.27 Scores on a Scale | Standard Deviation 0.932 |
| Placebo (Normal Saline) | Change From Baseline in the Dressing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.82 Scores on a Scale | Standard Deviation 1.092 |
| Placebo (Normal Saline) | Change From Baseline in the Dressing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.55 Scores on a Scale | Standard Deviation 1.082 |
Secondary
Change From Baseline in the MAS-B Score of Shoulder Adductors Using a 6-Point Scale
The MAS-B is a 6-point scale used to evaluate spasticity based on grading the resistance encountered in the shoulder adductors by passively moving the shoulder adductor muscles through their range of motion. The score ranges from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). Scores are converted to a 0 to 5 grade. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.
Time frame: Baseline, Week 6
Population: Intent-to-Treat: all randomized patients who were analyzed according to randomization assignment, regardless of treatment actually received
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| onabotulinumtoxinA 500U | Change From Baseline in the MAS-B Score of Shoulder Adductors Using a 6-Point Scale | Baseline | 4.00 Scores on a Scale | Standard Deviation 0 |
| onabotulinumtoxinA 500U | Change From Baseline in the MAS-B Score of Shoulder Adductors Using a 6-Point Scale | Change from Baseline at Week 6 | -1.59 Scores on a Scale | Standard Deviation 1.263 |
| onabotulinumtoxinA 300U | Change From Baseline in the MAS-B Score of Shoulder Adductors Using a 6-Point Scale | Baseline | 4.06 Scores on a Scale | Standard Deviation 0.236 |
| onabotulinumtoxinA 300U | Change From Baseline in the MAS-B Score of Shoulder Adductors Using a 6-Point Scale | Change from Baseline at Week 6 | -1.39 Scores on a Scale | Standard Deviation 1.042 |
| Placebo (Normal Saline) | Change From Baseline in the MAS-B Score of Shoulder Adductors Using a 6-Point Scale | Baseline | 4.00 Scores on a Scale | Standard Deviation 0 |
| Placebo (Normal Saline) | Change From Baseline in the MAS-B Score of Shoulder Adductors Using a 6-Point Scale | Change from Baseline at Week 6 | -1.44 Scores on a Scale | Standard Deviation 1.004 |
Secondary
Change From Baseline in the Self-Care Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL)
The SIA-UL asks the patient to assess the impact of upper limb spasticity in his/her daily life on a 19-item scale. The scale covers impacts on activities of dressing, showering/bathing, and self-care. The SIA score ranged from 0 (not at all difficult) to 4 (extremely difficult) for each question. The self-care domain was calculated based on the average of 4 questions.
Time frame: Baseline, Week 6
Population: Intent-to-Treat: all randomized patients who were analyzed according to randomization assignment, regardless of treatment actually received
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| onabotulinumtoxinA 500U | Change From Baseline in the Self-Care Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.58 Scores on a Scale | Standard Deviation 1.234 |
| onabotulinumtoxinA 500U | Change From Baseline in the Self-Care Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.26 Scores on a Scale | Standard Deviation 0.779 |
| onabotulinumtoxinA 300U | Change From Baseline in the Self-Care Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.21 Scores on a Scale | Standard Deviation 0.667 |
| onabotulinumtoxinA 300U | Change From Baseline in the Self-Care Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.61 Scores on a Scale | Standard Deviation 1.189 |
| Placebo (Normal Saline) | Change From Baseline in the Self-Care Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.48 Scores on a Scale | Standard Deviation 1.094 |
| Placebo (Normal Saline) | Change From Baseline in the Self-Care Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.61 Scores on a Scale | Standard Deviation 1.086 |
Secondary
Change From Baseline in the Showering/Bathing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL)
The SIA-UL asks the patient to assess the impact of upper limb spasticity his/her daily life on a 19-item scale. The scale covers impacts on activities of dressing, showering/bathing, and self-care. The SIA score ranged from 0 (not at all difficult) to 4 (extremely difficult) for each question. The showering/bathing domain was based on a single question.
Time frame: Baseline, Week 6
Population: Intent-to-Treat: all randomized patients who were analyzed according to randomization assignment, regardless of treatment actually received
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| onabotulinumtoxinA 500U | Change From Baseline in the Showering/Bathing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.71 Scores on a Scale | Standard Deviation 1.231 |
| onabotulinumtoxinA 500U | Change From Baseline in the Showering/Bathing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.62 Scores on a Scale | Standard Deviation 1.147 |
| onabotulinumtoxinA 300U | Change From Baseline in the Showering/Bathing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.69 Scores on a Scale | Standard Deviation 1.263 |
| onabotulinumtoxinA 300U | Change From Baseline in the Showering/Bathing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.36 Scores on a Scale | Standard Deviation 1.247 |
| Placebo (Normal Saline) | Change From Baseline in the Showering/Bathing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Baseline | 2.58 Scores on a Scale | Standard Deviation 1.188 |
| Placebo (Normal Saline) | Change From Baseline in the Showering/Bathing Domain Score on the Spasticity Impact Assessment-Upper Limb (SIA-UL) | Change from Baseline at Week 6 | -0.51 Scores on a Scale | Standard Deviation 1.064 |