MEDITOXIN® Versus BOTOX® in the Treatment of Post-stroke Spasticity of the Upper Limb Spasticity

Study Overview
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Brief Summary
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This study is a randomized, double blind, multi-center, active drug controlled, phase III clinical trial to compare the efficacy and safety of MEDITOXIN® versus BOTOX® in treatment of post stroke upper limb(wrist, finger, thumb) spasticity Approximately 196 subjects(1:1 group ratio)will be enrolled. Subjects will receive a single treatment of intramuscular Investigational product up to 360U. The subjects will be observed every 4 weeks until 12 weeks post injection. Outcome measures include Modified Ashworth Scale (MAS), Disability Assessment Scale (DAS), Global Assessment Scale(patient or caregiver/investigator) and Carer burden scale. The primary efficacy endpoint is the change from baseline at week 4 for wrist flexor muscle tone as measured on the Modified Ashworth Scale. Safety parameters will also be measured including adverse events, vital signs and clinical laboratory tests (haematology, serum chemistry and urinanalysis).

Detailed Description
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Each completed subject will attend 4 5 clinic visits. The maximum study duration is 15 weeks. Only one upper limb (eligible inclusion/exclusion criteria) will be injected and evaluated in the study. Maximun injection dose is 360U.

Official Title
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A Randomized, Double Blind, Multi-center, Active Drug Controlled Clinical Trial to Compare the Efficacy and Safety of MEDITOXIN® Versus BOTOX® in Treatment of Post Stroke Upper Limb Spasticity

Conditions
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Spasticity

Intervention / Treatment
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* Drug: Botulinum toxin type A
* Drug: Botulinum Toxin type A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥ 20 years ≥ 6 weeks since the last stroke ≥ 2 points in the focal spasticity of wrist flexor and ≥ 1 points at least one of elbow flexor and finger flexor as measured on MAS(0 to 4) Targeted one functional disability item (i.e., hygiene, dressing, pain, or cosmesis) with a rating of 2 or greater on DAS (0 to 3) Informed consent has been obtained. Exclusion Criteria: Neuromuscular disorders such as Lambert-Eaton syndrome, myasthenia gravis, or amyotrophic lateral sclerosis History(within 6 months of screening visit) or planned(during study period) treatment with phenol or alcohol injection or surgery in the target limb History(within 6 months of screening visit) or planned(during study period) treatment with tendon lengthening in the target limb Fixed joint/muscle contracture Severe atrophy Concurrent treatment with an intrathecal baclofen History(within 3 months of screening visit) Planned(during study period) treatment with Botulinum Toxin Known allergy or sensitivity to study medication or its components Concurrent or planed Muscle relaxants and/or benzodiazepine medication If patient has taken these medication stable from one month before screening and no treatment changes are not planned during the study, participation is allowed. Current Physical, occupational, Splinting therapy If these therapy regimens will be permitted if they has been stable in the one month before screening;no treatment and no changes are planned during the study. Patient who are participating in other clinical trials at the screening Females who are pregnant, breatfeeding,or planning a pregnancy during the study period, or female of childbearing potential, not using a reliable means of centraception. Patients who are not eligible for this study at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 20 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: Meditoxin®<br>Botulinum toxin type A | Drug: Botulinum toxin type A<br>* Botulinum toxin type A<br>* Other names: Neuronox®, Siax®;|
| Active Comparator: Botox®<br>Botulinum Toxin type A | Drug: Botulinum Toxin type A<br>* Botulinum Toxin type A<br>* Other names: Botox®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MAS(Modified Ashworth Scale) of Wrist Flexor | Change from baseline at week 4 for wrist flexor muscle tone as measured on the MAS(Modified Ashworth Scale). The Modified Ashworth Scale 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 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MAS(Modified Ashworth Scale) of Wrist Flexor | Change from baseline at week 8 and 12 for wrist flexor muscle tone as measured on the MAS(Modified Ashworth Scale). The Modified Ashworth Scale 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, week 8 and week 12 | 
| MAS(Modified Ashworth Score) of Elbow Flexor | Change from baseline at week 4, week 8 and 12 for elbow flexor muscle tone as measured on the MAS(Modified Ashworth Scale). The Modified Ashworth Scale 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, week 4, week 8 and week 12 | 
| MAS(Modified Ashworth Score) of Finger Flexor | Change from baseline at week 4, week 8 and 12 for finger flexor muscle tone as measured on the MAS(Modified Ashworth Scale). The Modified Ashworth Scale 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, week 4, week 8 and week 12 | 
| MAS(Modified Ashworth Score) of Thumb Flexor | Change from baseline at week 4, 8, 12 for thumb flexor muscle tone as measured on MAS. The Modified Ashworth Scale 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, week 4, week 8 and week 12 | 
| Improvement Rate on the MAS(Modified Ashworth Score) of Wrist Flexor | Improvement in the injected site muscle tone at week 4, 8 and 12 as measured by MAS(Modified Ashworth Score) of wrist flexor. * A treatment response is defined as 1-point improvement on the MAS(Modified Ashworth Score) of injection site. | week 4, week 8, week 12 | 
| Improvement Rate on the MAS(Modified Ashworth Score) of Elbow Flexor | Improvement in the injected site muscle tone at week 4, 8 and 12 as measured by MAS(Modified Ashworth Score) of elbow flexor. * A treatment response is defined as 1-point improvement on the MAS(Modified Ashworth Score) of injection site | week 4, week 8, week 12 | 
| Improvement Rate on the MAS(Modified Ashworth Score) of Finger Flexor | Improvement in the injected site muscle tone at week 4, 8 and 12 as measured by MAS(Modified Ashworth Score) of finger flexor. * A treatment response is defined as 1-point improvement on the MAS(Modified Ashworth Score) of injection site. | week 4, week 8, week 12 | 
| Improvement Rate on the MAS(Modified Ashworth Score) of Thumb Flexor | Improvement in the injected site muscle tone at week 4, 8 and 12 as measured by MAS(Modified Ashworth Score) of thumb flexor. * A treatment response is defined as 1-point improvement on the MAS(Modified Ashworth Score) of injection site. | week 4, week 8, week 12 | 
| DAS(Disability Assessment Scale) of Hygiene | Change From Baseline to week 4, 8, 12 in the DAS(Disability Assessment Scale) for the Principal Therapeutic Target as 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). | Baseline, week 4, week 8 and week 12 | 
| DAS(Disability Assessment Scale) of Dressing | Change From Baseline to week 4, 8, 12 in the DAS(Disability Assessment Scale) for the Principal Therapeutic Target as 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). | Baseline, week 4, week 8 and week 12 | 
| DAS(Disability Assessment Scale) of Limb Position | Change From Baseline to week 4, 8, 12 in the DAS(Disability Assessment Scale) for the Principal Therapeutic Target as 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). | Baseline, week 4, week 8 and week 12 | 
| DAS(Disability Assessment Scale) of Pain | Change From Baseline to week 4, 8, 12 in the DAS(Disability Assessment Scale) for the Principal Therapeutic Target as 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). | Baseline, week 4, week 8 and week 12 | 
| Global Assessment by Investigator | Global assessment evaluated by investigator at week 12 after injection | week 12 | 
| Global Assessment by Patient or Caregiver | Global assessment evaluated by patient or caregiver at week 12 after injection | week 12 | 
| Carer Burden Scale of Cleaning the Palm | The Carer Burden Scale evaluates the impact of antispastic medication on the physical burden of the carer. It was assessed on a 5-point Likert scale which values ranges from 0 (=no difficulty) to 4 (=cannot do the task). | Baseline, week 4, week 8 and week 12 | 
| Carer Burden Scale of Cutting the Finger-nails | The Carer Burden Scale evaluates the impact of antispastic medication on the physical burden of the carer. It was assessed on a 5-point Likert scale which values ranges from 0 (=no difficulty) to 4 (=cannot do the task). | Baseline, week 4, week 8 and week 12 | 
| Carer Burden Scale of Putting Shirts on | The Carer Burden Scale evaluates the impact of antispastic medication on the physical burden of the carer. It was assessed on a 5-point Likert scale which values ranges from 0 (=no difficulty) to 4 (=cannot do the task). | Baseline, week 4, week 8 and week 12 | 
| Carer Burden Scale of Cleaning the Armpit | The Carer Burden Scale evaluates the impact of antispastic medication on the physical burden of the carer. It was assessed on a 5-point Likert scale which values ranges from 0 (=no difficulty) to 4 (=cannot do the task). | Baseline, week 4, week 8 and week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spasticity, upperlimb, Botulinum toxin