Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Spasticity in the Leg After a Stroke

Study Overview
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Brief Summary
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The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg are effective in treating patients with increased muscle tension/uncontrollable muscle stiffness (spasticity) after a stroke.

Official Title
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Prospective, Double-blind, Placebo-controlled, Randomized, Multi-center Study With an Open-label Extension Period to Investigate the Efficacy and Safety of NT 201 in the Treatment of Post-stroke Spasticity of the Lower Limb

Conditions
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Post-stroke Spasticity of the Lower Limb

Intervention / Treatment
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* Drug: IncobotulinumtoxinA (400 Units)
* Drug: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18-80 yrs Lower limb spasticity Time since stroke greater than 3 months Need for 400 U Botulinum toxin type A Exclusion Criteria: Body weight below 50kg Fixed contractures of the lower limb Generalized disorders of muscle activity like Myasthenia gravis that preclude use of Botulinum toxin type A Infection at the injection site

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: IncobotulinumtoxinA (Xeomin) 400 Units<br>IncobotulinumtoxinA (Xeomin, also known as NT 201 or Botulinum toxin type A (150 kiloDalton), free from complexing proteins) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection. | Drug: IncobotulinumtoxinA (400 Units)<br>* Main period: One injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400 units, total volume 8.0 mL; Mode of administration: intramuscular injection.<br>|
| Placebo Comparator: Placebo Comparator Arm<br>Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection. | Drug: Placebo Comparator<br>* Main period: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl, corresponding total placebo volume 8.0 mL; Mode of administration: intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Ashworth Scale (AS) for Plantar Flexors at Week 4 | The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). | Baseline and Week 4 | 
| Co-primary Variable: Investigator's Global Assessment of Efficacy at Week 12 | A 4-point Likert scale will be used with the ratings 1 = very good, 2 = good, 3 = moderate, and 4 = poor. Investigator's Global Assessment of Efficacy at Week 12 will be a co-primary outcome measure to fulfill post marketing commitments for U.S. regulatory authorities only. Elsewhere, it will be a secondary outcome measure. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate for Plantar Flexors at All Post-Baseline Visits for Subjects With an Improvement (Reduction) of at Least 1 Point From Baseline in the Ashworth Scale (AS) | Response is defined as an improvement (reduction) of the plantar flexor Ashworth Score by at least one score point. The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). | Week 4, 8, and 12 | 
| Ashworth Scale (AS) for Plantar Flexors at All Post-Baseline Visits | The AS is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). Here, 'n' specifies those subjects who were evaluated for this outcome measure at given time point. | Baseline, Week 4, 8, and 12 |