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

Phase 3

Completed

Conditions: Spasticity

Interventions: Drug: Botulinum Toxin type A

Registration Number: NCT01313767

Lead Sponsor: Medy-Tox

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 196

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Meditoxin®	Botulinum Toxin type A	Botulinum toxin type A
Botox®	Botulinum Toxin type A	Botulinum Toxin type A

Primary Outcome Measures

Name	Time	Method
MAS(Modified Ashworth Scale) of Wrist Flexor	Baseline and 4 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Improvement Rate on the MAS(Modified Ashworth Score) of Wrist Flexor	week 4, week 8, week 12	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.
Global Assessment by Patient or Caregiver	week 12	Global assessment evaluated by patient or caregiver at week 12 after injection
MAS(Modified Ashworth Scale) of Wrist Flexor	Baseline, week 8 and week 12	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).
MAS(Modified Ashworth Score) of Elbow Flexor	Baseline, week 4, week 8 and week 12	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).
MAS(Modified Ashworth Score) of Finger Flexor	Baseline, week 4, week 8 and week 12	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).
MAS(Modified Ashworth Score) of Thumb Flexor	Baseline, week 4, week 8 and week 12	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).
Improvement Rate on the MAS(Modified Ashworth Score) of Elbow Flexor	week 4, week 8, week 12	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
Improvement Rate on the MAS(Modified Ashworth Score) of Thumb Flexor	week 4, week 8, week 12	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.
Carer Burden Scale of Cutting the Finger-nails	Baseline, week 4, week 8 and week 12	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).
Carer Burden Scale of Cleaning the Armpit	Baseline, week 4, week 8 and week 12	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).
Improvement Rate on the MAS(Modified Ashworth Score) of Finger Flexor	week 4, week 8, week 12	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.
Carer Burden Scale of Cleaning the Palm	Baseline, week 4, week 8 and week 12	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).
DAS(Disability Assessment Scale) of Hygiene	Baseline, week 4, week 8 and week 12	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).
Carer Burden Scale of Putting Shirts on	Baseline, week 4, week 8 and week 12	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).
DAS(Disability Assessment Scale) of Dressing	Baseline, week 4, week 8 and week 12	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).
DAS(Disability Assessment Scale) of Limb Position	Baseline, week 4, week 8 and week 12	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).
DAS(Disability Assessment Scale) of Pain	Baseline, week 4, week 8 and week 12	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).
Global Assessment by Investigator	week 12	Global assessment evaluated by investigator at week 12 after injection