BOTOX® Treatment in Adult Patients With Post-Stroke Lower Limb Spasticity

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of BOTOX® in the treatment of adult post-stroke lower limb spasticity.

Conditions
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Muscle Spasticity

Intervention / Treatment
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* Biological: botulinum toxin Type A
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of post-stroke lower limb spasticity for at least 3 months Minimum body weight of 50 kg Never treated with botulinum toxin of any serotype for any reason, or if previously treated with botulinum toxin of any serotype, if previously treated for spasticity in the affected lower limb, must have been administered 20 weeks before Day 1, or if previously treated for any other indication must have been administered ≥12 weeks prior to Day 1 Exclusion Criteria: Spasticity in the opposite leg that requires treatment Casting of the study limb within 6 months or planned casting during the first 12 weeks of the study Treatment modalities in the study limb including ultrasound, electrical nerve stimulation, electrical stimulation, acupuncture within 1 month of Day 1 or treatments planned during the study Not able to perform 10 meter walking test independently with or without assistive device Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: botulinum toxin Type A<br>Double-Blind Study Phase (12 weeks): On Day 1, botulinum toxin Type A 300 U will be given by intramuscular injections into specified muscles of the lower limb, and an optional dose of 100 U may be injected into additional lower limb muscles. Open Label Study Phase: Up to 3 treatments with botulinum toxin Type A up to 400 U will be given by intramuscular injections to the lower limb approximately every 12 weeks over a 42 week period. | Biological: botulinum toxin Type A<br>* Double-Blind Study Phase (12 weeks): On Day 1, botulinum toxin Type A 300 U will be given by intramuscular injections into specified muscles of the lower limb, and an optional dose of 100 U may be injected into additional lower limb muscles. Open Label Study Phase: Up to 3 treatments with botulinum toxin Type A up to 400 U will be given by intramuscular injections to the lower limb approximately every 12 weeks over a 42 week period.<br>* Other names: onabotulinumtoxin A;|
| Other: Normal Saline (Placebo) Followed by botulinum toxin Type A<br>Double-Blind Study Phase (12 weeks): On Day 1, normal saline (placebo) will be given by intramuscular injections into specified muscles of the lower limb, and optional injections may be administered into additional lower limb muscles. Open Label Study Phase: Up to 3 treatments with botulinum toxin Type A up to 400 U will be given by intramuscular injections to the lower limb approximately every 12 weeks over a 42 week period. | Biological: botulinum toxin Type A<br>* Double-Blind Study Phase (12 weeks): On Day 1, botulinum toxin Type A 300 U will be given by intramuscular injections into specified muscles of the lower limb, and an optional dose of 100 U may be injected into additional lower limb muscles. Open Label Study Phase: Up to 3 treatments with botulinum toxin Type A up to 400 U will be given by intramuscular injections to the lower limb approximately every 12 weeks over a 42 week period.<br>* Other names: onabotulinumtoxin A;Drug: Normal Saline<br>* Double-Blind Study Phase (12 weeks): On Day 1, normal saline (placebo) will be given by intramuscular injections into specified muscles of the lower limb, and optional injections may be administered into additional lower limb muscles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of Ankle Plantar 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 ankle flexors by passively moving the ankle plantar 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. The average of the weeks 4 and 6 MAS-B ankle change from baseline is the primary end point. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. | Baseline, 6 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of Optional Muscles 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 optional muscles by passively moving the muscles through their range of motion. Optional muscles treated include: Rectus Femoris, Flexor Digitorum Longus, Flexor Hallucis Longus, and Extensor Hallucis. The scores range 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. | Baseline, Week 6 | 
| Clinical Global Impression (CGI) of Overall Change by Physician Using a 9-Point Scale | The CGI is a 9-point scale evaluating change from baseline status by the Physician. Scores range from +4 (very marked improvement) to -4 (very marked worsening). The average of the weeks 4 and 6 CGI by Physician score is used as a secondary end point. Higher scores indicate a greater improvement from baseline. | Baseline, 6 weeks | 
| Goal Attainment Scores on the 6-Point Physician-Assessed Goal Attainment Scale (GAS) | The physician-assessed GAS is an individualized, goal-oriented 6-point scale used to track functional improvement toward active and passive goals. GAS scoring ranged from -3 to 2 (-3 = worse than start; 0 = expected goal/attained the defined therapeutic goal; 2 = much more than expected/improvements clearly exceeded the defined therapeutic goal). Active and Passive Goal scores are presented. | Week 8 | 
| Change From Baseline in Average Pain Score While Walking on the 11-Point Pain Scale | The patient is asked to select a number that best describes his/her pain while walking 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. | Baseline, Week 6 |