Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Spasticity in the Arm 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 upper limb are effective in treating spasticity in patients after stroke.

Detailed Description
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The study consists of a randomized, double-blind, placebo-controlled, parallel-group, single-dose main period followed by an open-label, non-controlled, repeated-dose extension period (Open-Label Extension Period - OLEX).

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 Upper Limb

Conditions
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Post-stroke Spasticity of the Upper 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: Upper 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 upper 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DB IncobotulinumtoxinA (Xeomin) (400 U)<br>IncobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind (DB), randomized treatment assignment | 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>* Other names: Xeomin;|
| Placebo Comparator: DB Placebo Comparator<br>Placebo to incobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind (DB), randomized treatment assignment | 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) Score of Primary Target Clinical Pattern | Primary target clinical pattern was defined by investigator for each subject at baseline visit and was either flexed wrist or clenched fist or flexed elbow. The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 | 
| Investigator's Global Impression of Change | This is the co-primary outcome measure. The Global Impression of Change Scale [GICS] is used to measure the investigator's impression of change due to treatment. The response option is a common 7-point Likert scale that ranges from -3 = very much worse to +3 = very much improved. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rates on the Ashworth Scale at Week 4 Calculated for the Muscle Group Flexed Wrist | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 4 | 
| Response Rates on the Ashworth Scale at Week 8 Calculated for the Muscle Group Flexed Wrist | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 8 | 
| Response Rates on the Ashworth Scale at Week 12 Calculated for the Muscle Group Flexed Wrist | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 12 | 
| Response Rates on the Ashworth Scale at Week 4 Calculated for the Muscle Group Flexed Elbow | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 4 | 
| Response Rates on the Ashworth Scale at Week 8 Calculated for the Muscle Group Flexed Elbow | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 8 | 
| Response Rates on the Ashworth Scale at Week 12 Calculated for the Muscle Group Flexed Elbow | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 12 | 
| Response Rates on the Ashworth Scale at Week 4 Calculated for the Muscle Group Clenched Fist | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 4 | 
| Response Rates on the Ashworth Scale at Week 8 Calculated for the Muscle Group Clenched Fist | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 8 | 
| Response Rates on the Ashworth Scale at Week 12 Calculated for the Muscle Group Clenched Fist | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 12 | 
| Response Rates on the Ashworth Scale at Week 4 Calculated for the Muscle Group Thumb-in-palm | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 4 | 
| Response Rates on the Ashworth Scale at Week 8 Calculated for the Muscle Group Thumb-in-palm | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 8 | 
| Response Rates on the Ashworth Scale at Week 12 Calculated for the Muscle Group Thumb-in-palm | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 12 | 
| Response Rates on the Ashworth Scale at Week 4 Calculated for the Muscle Group Pronated Forearm | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 4 | 
| Response Rates on the Ashworth Scale at Week 8 Calculated for the Muscle Group Pronated Forearm | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 8 | 
| Response Rates on the Ashworth Scale at Week 12 Calculated for the Muscle Group Pronated Forearm | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 12 | 
| Changes From Baseline to Week 4 in Ashworth Scale Score for Treated Muscle Group Flexed Wrist. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 | 
| Changes From Baseline to Week 8 in Ashworth Scale Score for Treated Muscle Group Flexed Wrist. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 8 | 
| Changes From Baseline to Week 12 in Ashworth Scale Score for Treated Muscle Group Flexed Wrist. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 12 | 
| Changes From Baseline to Week 4 in Ashworth Scale Score for Treated Muscle Group Flexed Elbow. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 | 
| Changes From Baseline to Week 8 in Ashworth Scale Score for Treated Muscle Group Flexed Elbow. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 8 | 
| Changes From Baseline to Week 12 in Ashworth Scale Score for Treated Muscle Group Flexed Elbow. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 12 | 
| Changes From Baseline to Week 4 in Ashworth Scale Score for Treated Muscle Group Clenched Fist. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 | 
| Changes From Baseline to Week 8 in Ashworth Scale Score for Treated Muscle Group Clenched Fist. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 8 | 
| Changes From Baseline to Week 12 in Ashworth Scale Score for Treated Muscle Group Clenched Fist. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 12 | 
| Changes From Baseline to Week 4 in Ashworth Scale Score for Treated Muscle Group Thumb-in-palm. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 | 
| Changes From Baseline to Week 8 in Ashworth Scale Score for Treated Muscle Group Thumb-in-palm. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 8 | 
| Changes From Baseline to Week 12 in Ashworth Scale Score for Treated Muscle Group Thumb-in-palm. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 12 | 
| Changes From Baseline to Week 4 in Ashworth Scale Score for Treated Muscle Group Pronated Forearm. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 | 
| Changes From Baseline to Week 8 in Ashworth Scale Score for Treated Muscle Group Pronated Forearm. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 8 | 
| Changes From Baseline to Week 12 in Ashworth Scale Score for Treated Muscle Group Pronated Forearm. | The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize 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 12 | 
| Changes From Baseline to Week 4 in Disability Assessment Scale - Principal Therapeutic Target Domain | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 4 | 
| Changes From Baseline to Week 8 in Disability Assessment Scale - Principal Therapeutic Target Domain | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 8 | 
| Changes From Baseline to Week 12 in Disability Assessment Scale - Principal Therapeutic Target Domain | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 12 | 
| Changes From Baseline to Week 4 in Disability Assessment Scale - Domain Hygiene | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 4 | 
| Changes From Baseline to Week 8 in Disability Assessment Scale - Domain Hygiene | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 8 | 
| Changes From Baseline to Week 12 in Disability Assessment Scale - Domain Hygiene | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 12 | 
| Changes From Baseline to Week 4 in Disability Assessment Scale - Domain Dressing | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 4 | 
| Changes From Baseline to Week 8 in Disability Assessment Scale - Domain Dressing | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 8 | 
| Changes From Baseline to Week 12 in Disability Assessment Scale - Domain Dressing | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 12 | 
| Changes From Baseline to Week 4 in Disability Assessment Scale - Domain Limb Position | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 4 | 
| Changes From Baseline to Week 8 in Disability Assessment Scale - Domain Limb Position | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 8 | 
| Changes From Baseline to Week 12 in Disability Assessment Scale - Domain Limb Position | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 12 | 
| Changes From Baseline to Week 4 in Disability Assessment Scale - Domain Pain | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 4 | 
| Changes From Baseline to Week 8 in Disability Assessment Scale - Domain Pain | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 8 | 
| Changes From Baseline to Week 12 in Disability Assessment Scale - Domain Pain | The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability). | Week 12 | 
| Response Rates on the Ashworth Scale at Week 4 Calculated for the Primary Target Clinical Pattern | Primary target clinical pattern was defined by investigator for each subject at baseline visit and was either flexed wrist or clenched fist or flexed elbow. Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 4 | 
| Response Rates on the Ashworth Scale at Week 8 Calculated for the Primary Target Clinical Pattern | Primary target clinical pattern was defined by investigator for each subject at baseline visit and was either flexed wrist or clenched fist or flexed elbow. Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 8 | 
| Response Rates on the Ashworth Scale at Week 12 Calculated for the Primary Target Clinical Pattern | Primary target clinical pattern was defined by investigator for each subject at baseline visit and was either flexed wrist or clenched fist or flexed elbow. Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis. | Week 12 |