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

• Sponsor: Medy-Tox (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01313767
• Collaborator: (none)
• Enrollment: 196
• Location: 1
• Arms: 2
• Duration (Months): 11.1
• Patients Per Site Per Month: 17.7

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Spasticity	Drug: Botulinum toxin type A; Drug: Botulinum Toxin type A	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 196 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Meditoxin® Botulinum toxin type A	Drug: Botulinum toxin type A; Botulinum toxin type A; Other Names: Neuronox®, Siax®
Active Comparator: Botox® Botulinum Toxin type A	Drug: Botulinum Toxin type A; Botulinum Toxin type A; Other Names: Botox®

Outcome Measures

Primary Outcome Measures

1. 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

1. 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).

2. 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).

3. 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).

4. 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).

5. 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.

6. 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

7. 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.

8. 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.

9. 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).

10. 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).

11. 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).

12. 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).

13. Global Assessment by Investigator [week 12]

    Global assessment evaluated by investigator at week 12 after injection

14. Global Assessment by Patient or Caregiver [week 12]

    Global assessment evaluated by patient or caregiver at week 12 after injection

15. 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).

16. 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).

17. 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).

18. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female patients ≥ 20 years

2. ≥ 6 weeks since the last stroke

3. ≥ 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)

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)

5. Informed consent has been obtained.

Exclusion Criteria:

1. Neuromuscular disorders such as Lambert-Eaton syndrome, myasthenia gravis, or amyotrophic lateral sclerosis

2. History(within 6 months of screening visit) or planned(during study period) treatment with phenol or alcohol injection or surgery in the target limb

3. History(within 6 months of screening visit) or planned(during study period) treatment with tendon lengthening in the target limb

4. Fixed joint/muscle contracture

5. Severe atrophy

6. Concurrent treatment with an intrathecal baclofen

7. History(within 3 months of screening visit) Planned(during study period) treatment with Botulinum Toxin

8. Known allergy or sensitivity to study medication or its components

9. 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.

1. 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.

1. Patient who are participating in other clinical trials at the screening

2. 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.

3. Patients who are not eligible for this study at the discretion of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Hospital	Seoul		Korea, Republic of

Sponsors and Collaborators

• Medy-Tox

Investigators

• Principal Investigator: Moon Suk Bang, Ph.D, Seoul National Universtiy Hospital, 101 Daehak-ro Jong-gu, Seoul 110-744, Korea
• Principal Investigator: Min Ho Chun, Ph.D, Asan Medical Center, 388-1 Pungnap-2 dong, Songpa-Gu, Seoul, 138-736, Korea
• Principal Investigator: Nam Jong Baik, Ph. D, University Bundang Hospital, Seoul National Univ. Bundang Hospital, Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea
• Principal Investigator: Si Uk Lee, Ph.D, SMG-SNU Boramae Medical Center, 41, Borame-Gill, Dong Gjak-Gu, Seoul, 156-707, Seoul, Korea
• Principal Investigator: Beom Seon Gwon, Ph.D, Dongguk University International Hospital, Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do, Korea

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medy-Tox
• ClinicalTrials.gov Identifier: NCT01313767
• Other Study ID Numbers: MT-PRT-ST01
• First Posted: Mar 14, 2011
• Last Update Posted: Mar 29, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Medy-Tox: spasticity; upperlimb; Botulinum toxin
• Additional relevant MeSH terms: Muscle Spasticity; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Recruitment Details	In this study, total 208 patients were screened and total 196 subjects (98 subjects per group) were randomized, except 12 screening-failures, at 5 study sites.
Pre-assignment Detail	Total 9 subjects were prematurely discontinued from the study due to unmet inclusion/exclusion criteria found after randomization, AEs/SAEs, consent withdrawal and follow-up lost: 7 subjects in study group (7.14%) and 2 subjects in control group (2.04%). Thus total 187 subjects (91 in study group; 96 in control group) completed the study.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Clostridium Botulinum toxin type A, up to total 360U injected into selected sites, Intra-muscle	Clostridium Botulinum toxin type A, up to total 360U injected into selected sites, Intra-muscle
Period Title: Overall Study
STARTED	98	98
COMPLETED	91	96
NOT COMPLETED	7	2

Baseline Characteristics

Arm/Group Title	Meditoxin®	Botox®	Total
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A	Total of all reporting groups
Overall Participants	94	98	192
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	67 71.3%	69 70.4%	136 70.8%
>=65 years	27 28.7%	29 29.6%	56 29.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.54 (11.03)	56.99 (13.01)	57.26 (12.05)
Sex: Female, Male (Count of Participants)
Female	29 30.9%	31 31.6%	60 31.3%
Male	65 69.1%	67 68.4%	132 68.8%
Region of Enrollment (participants) [Number]
Korea, Republic of	94 100%	98 100%	192 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	65.51 (10.27)	62.94 (9.67)	64.18 (10.02)

Outcome Measures

1. Primary Outcome

Title	MAS(Modified Ashworth Scale) of Wrist Flexor
Description	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).
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 94 subjects receiving Meditoxin and 98 subjects for Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	94	98
Baseline	2.41 (0.61)	2.52 (0.66)
Week 4	1.02 (0.81)	0.96 (0.64)
Change(Week4-Baseline)	-1.39 (0.79)	-1.56 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	The difference between the two groups was provided with 95% CI. If the upper limit of CI is no greater than 0.45 (non-inferiority margin), the study group was determined not inferior to the control group. Additionally, difference between groups in change from baseline to week 4 in wrist flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	90% of the power, 0.45 of non-inferiority margin
Statistical Test of Hypothesis	p-Value	0.1347
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	MAS(Modified Ashworth Scale) of Wrist Flexor
Description	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).
Time Frame	Baseline, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 94 subjects receiving Meditoxin and 98 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	94	98
Baseline	2.41 (0.61)	2.52 (0.66)
Week 8	1.07 (0.78)	1.04 (1.16)
Week 12	1.16 (0.86)	1.16 (0.66)
Change(Week 8 - Baseline)	-1.35 (0.77)	-1.48 (0.87)
Change(Week12 - Baseline)	-1.25 (0.78)	-1.36 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in wrist flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2591
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in wrist flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3395
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	MAS(Modified Ashworth Score) of Elbow Flexor
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 87 subjects receiving Meditoxin and 94 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	87	94
Baseline	2.33 (0.75)	2.18 (0.65)
Week 4	1.26 (0.73)	1.30 (0.58)
Week 8	1.36 (0.54)	1.41 (0.58)
Week 12	1.45 (0.68)	1.52 (0.60)
Change(Week 4 - Baseline)	-1.07 (0.73)	-0.87 (0.71)
Change(Week 8 - Baseline)	-0.97 (0.74)	-0.77 (0.72)
Change(Week 12 - Baseline)	-0.88 (0.75)	-0.65 (0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in elbow flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0675
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in elbow flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0605
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in elbow flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0429
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	MAS(Modified Ashworth Score) of Finger Flexor
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 82 subjects receiving Meditoxin and 83 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	82	83
Baseline	2.37 (0.80)	2.48 (0.75)
Week 4	1.01 (0.67)	1.05 (0.66)
Week 8	1.15 (0.62)	1.17 (0.66)
Week 12	1.20 (0.68)	1.30 (0.66)
Change(Week 4 - Baseline)	-1.36 (0.90)	-1.42 (0.94)
Change(Week 8 - Baseline)	-1.23 (0.89)	-1.30 (0.91)
Change(Week 12 - Baseline)	-1.18 (0.90)	-1.16 (0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in finger flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6954
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in finger flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6024
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in finger flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9316
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	MAS(Modified Ashworth Score) of Thumb Flexor
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 54 subjects receiving Meditoxin and 58 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	54	58
Baseline	1.94 (0.73)	1.94 (0.74)
Week 4	0.89 (0.71)	0.69 (0.66)
Week 8	1.01 (0.67)	0.84 (0.77)
Week 12	1.06 (0.84)	0.96 (0.69)
Change(Week 4 - Baseline)	-1.06 (0.85)	-1.25 (0.83)
Change(Week 8 - Baseline)	-0.94 (0.85)	-1.09 (0.85)
Change(Week 12 - Baseline)	-0.89 (0.99)	-0.98 (0.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in thumb flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2284
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.19
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in thumb flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3221
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.15
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in thumb flexor MAS score was compared using two sample t-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5930
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Improvement Rate on the MAS(Modified Ashworth Score) of Wrist Flexor
Description	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.
Time Frame	week 4, week 8, week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 94 subjects receiving Meditoxin and 98 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	94	98
Week 4	77	88
Week 8	77	80
Week 12	71	77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 4 from baseline in wrist flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1585
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 8 from baseline in wrist flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9596
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0028
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 12 from baseline in wrist flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6164
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.0304
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Improvement Rate on the MAS(Modified Ashworth Score) of Elbow Flexor
Description	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
Time Frame	week 4, week 8, week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 87 subjects receiving Meditoxin and 94 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	87	94
Week 4	56	52
Week 8	49	42
Week 12	46	39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 4 from baseline in elbow flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1802
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0980
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 8 from baseline in elbow flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1176
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.1164
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 12 from baseline in elbow flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1252
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.1138
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Improvement Rate on the MAS(Modified Ashworth Score) of Finger Flexor
Description	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.
Time Frame	week 4, week 8, week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 82 subjects receiving Meditoxin and 83 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	82	83
Week 4	58	64
Week 8	51	60
Week 12	47	54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 4 from baseline in finger flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3431
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0980
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 8 from baseline in finger flexor was compared using Pearson's chi-square test
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1329
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.1097
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 12 from baseline in finger flexor was compared using Pearson's chi-square test
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2611
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0853
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Improvement Rate on the MAS(Modified Ashworth Score) of Thumb Flexor
Description	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.
Time Frame	week 4, week 8, week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 54 subjects receiving Meditoxin and 58 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	54	58
Week 4	34	41
Week 8	28	37
Week 12	27	30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 4 from baseline in thumb flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4623
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.0654
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 8 from baseline in thumb flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2007
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.1194
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency of responders who have improved at least 1-point on the MAS at week 12 from baseline in thumb flexor was compared using Pearson's chi-square test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8553
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0172
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	DAS(Disability Assessment Scale) of Hygiene
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 39 subjects receiving Meditoxin and 34 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	39	34
Baseline	2.62 (0.49)	2.74 (0.45)
Week 4	1.90 (1.02)	2.09 (0.87)
Week 8	1.85 (0.99)	2.12 (0.88)
Week 12	1.87 (0.98)	2.12 (0.84)
Change(Week 4 - Baseline)	-0.72 (0.79)	-0.65 (0.65)
Change(Week 8 - Baseline)	-0.77 (0.67)	-0.62 (0.65)
Change(Week 12 - Baseline)	-0.74 (0.75)	-0.62 (0.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in DAS score of hygiene was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6040
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in DAS score of hygiene was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3233
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in DAS score of hygiene was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4469
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	DAS(Disability Assessment Scale) of Dressing
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 11 subjects receiving Meditoxin and 15 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	11	15
Baseline	2.09 (0.30)	2.13 (0.35)
Week 4	1.30 (0.67)	1.07 (0.47)
Week 8	1.36 (0.50)	1.00 (0.55)
Week 12	1.27 (0.65)	1.00 (0.55)
Change(Week 4 - Baseline)	-0.70 (0.67)	-1.07 (0.47)
Change(Week 8 - Baseline)	-0.73 (0.47)	-1.14 (0.66)
Change(Week 12 - Baseline)	-0.82 (0.60)	-1.14 (0.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in DAS score of dressing was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1220
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in DAS score of dressing was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1016
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in DAS score of dressing was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2235
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.32
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	DAS(Disability Assessment Scale) of Limb Position
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 40 subjects receiving Meditoxin and 47 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	40	47
Baseline	2.50 (0.51)	2.45 (0.50)
Week 4	1.28 (0.55)	1.29 (0.54)
Week 8	1.27 (0.55)	1.25 (0.53)
Week 12	1.29 (0.56)	1.23 (0.47)
Change(Week 4 - Baseline)	-1.23 (0.62)	-1.15 (0.55)
Change(Week 8 - Baseline)	-1.23 (0.66)	-1.19 (0.54)
Change(Week 12 - Baseline)	-1.20 (0.69)	-1.21 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in DAS score of limb position was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5030
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in DAS score of limb position was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6934
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in DAS score of limb position was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9574
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	DAS(Disability Assessment Scale) of Pain
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 4 subjects receiving Meditoxin and 2 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	4	2
Baseline	2.00 (0.00)	2.00 (0.00)
Week 4	1.25 (0.50)	1.00 (0.00)
Week 8	0.75 (0.50)	1.00 (0.00)
Week 12	0.50 (0.58)	0.00 (0.00)
Change(Week 4 - Baseline)	-0.75 (0.50)	-1.00 (0.00)
Change(Week 8 - Baseline)	-1.25 (0.50)	-1.00 (0.00)
Change(Week 12 - Baseline)	-1.50 (0.58)	-2.00 (0.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in DAS score of pain was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7237
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.25
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in DAS score of pain was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7237
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in DAS score of pain was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4017
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Global Assessment by Investigator
Description	Global assessment evaluated by investigator at week 12 after injection
Time Frame	week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 94 subjects receiving Meditoxin and 98 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	94	98
Very good	19 20.2%	19 19.4%
Good	63 67%	56 57.1%
Moderate	10 10.6%	18 18.4%
Insufficient	1 1.1%	4 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency distribution of responders on the Global Assessment at week 12 was compared using Fisher's exact test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2346
	Comments
	Method	Fisher Exact
	Comments

15. Secondary Outcome

Title	Global Assessment by Patient or Caregiver
Description	Global assessment evaluated by patient or caregiver at week 12 after injection
Time Frame	week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 94 subjects receiving Meditoxin and 98 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	94	98
Very good	11 11.7%	10 10.2%
Good	39 41.5%	44 44.9%
Moderate	36 38.3%	35 35.7%
Insufficient	7 7.4%	8 8.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in frequency distribution of responders on the Global Assessment at week 12 was compared using Fisher's exact test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9513
	Comments
	Method	Fisher Exact
	Comments

16. Secondary Outcome

Title	Carer Burden Scale of Cleaning the Palm
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 92 subjects receiving Meditoxin and 98 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	92	98
Baseline	1.70 (1.16)	1.67 (1.17)
Week 4	1.26 (1.02)	1.34 (1.00)
Week 8	1.24 (0.96)	1.40 (1.09)
Week 12	1.18 (1.05)	1.44 (1.09)
Change(Week 4 - Baseline)	-0.40 (1.29)	-0.34 (1.10)
Change(Week 8 - Baseline)	-0.46 (1.24)	-0.28 (1.09)
Change(Week 12 - Baseline)	-0.51 (1.34)	-0.23 (1.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in carer burden scale of cleaning the palm was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8088
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in carer burden scale of cleaning the palm was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3702
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in carer burden scale of cleaning the palm was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1497
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Carer Burden Scale of Cutting the Finger-nails
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 92 subjects receiving Meditoxin and 98 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	92	98
Baseline	2.08 (1.34)	2.22 (1.27)
Week 4	1.58 (1.30)	1.89 (1.32)
Week 8	1.57 (1.25)	1.84 (1.37)
Week 12	1.59 (1.32)	1.81 (1.35)
Change(Week 4 - Baseline)	-0.47 (1.26)	-0.34 (1.17)
Change(Week 8 - Baseline)	-0.51 (1.29)	-0.39 (1.25)
Change(Week 12 - Baseline)	-0.49 (1.35)	-0.42 (1.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in carer burden scale of cutting the finger-nails was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9634
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in carer burden scale of cutting the finger-nails was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7302
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in carer burden scale of cutting the finger-nails was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7715
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Carer Burden Scale of Putting Shirts on
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 92 subjects receiving Meditoxin and 98 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	92	98
Baseline	1.79 (1.00)	1.64 (1.11)
Week 4	1.46 (0.97)	1.42 (1.10)
Week 8	1.34 (0.96)	1.28 (0.97)
Week 12	1.32 (1.05)	1.30 (1.07)
Change(Week 4 - Baseline)	-0.32 (1.12)	-0.22 (0.98)
Change(Week 8 - Baseline)	-0.46 (1.11)	-0.37 (1.17)
Change(Week 12 - Baseline)	-0.48 (1.13)	-0.35 (1.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in carer burden scale of putting shirts on was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9362
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in carer burden scale of putting shirts on was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7998
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in carer burden scale of putting shirts on was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5436
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Carer Burden Scale of Cleaning the Armpit
Description	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).
Time Frame	Baseline, week 4, week 8 and week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set population which consisted of 92 subjects receiving Meditoxin and 98 Botox.

Arm/Group Title	Meditoxin®	Botox®
Arm/Group Description	Botulinum toxin type A	Botulinum Toxin type A
Measure Participants	92	98
Baseline	1.98 (1.21)	1.97 (1.27)
Week 4	1.56 (1.15)	1.71 (1.26)
Week 8	1.50 (1.16)	1.59 (1.29)
Week 12	1.42 (1.15)	1.69 (1.33)
Change(Week 4 - Baseline)	-0.39 (1.12)	-0.26 (1.20)
Change(Week 8 - Baseline)	-0.48 (1.12)	-0.38 (1.26)
Change(Week 12 - Baseline)	-0.55 (1.19)	-0.28 (1.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 4 in carer burden scale of cleaning the armpit was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7014
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 8 in carer burden scale of cleaning the armpit was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8884
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Meditoxin®, Botox®
	Comments	Difference between groups in change from baseline to week 12 in carer burden scale of cleaning the armpit was compared using wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2840
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	The subjects were observed every visit after signing an Informed consent form (visit 1) until 12 weeks post injection
Adverse Event Reporting Description	All AEs reported during the study period were tabulated and AE incidence was determined.
Arm/Group Title	Meditoxin®		Botox®
Arm/Group Description	Botulinum toxin type A		Botulinum Toxin type A
All Cause Mortality
	Meditoxin®		Botox®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Meditoxin®		Botox®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/98 (5.1%)		8/98 (8.2%)
Cardiac disorders
Myocardial infarction	1/98 (1%)	1	0/98 (0%)	0
Gastrointestinal disorders
Inguinal hernia	0/98 (0%)	0	1/98 (1%)	1
Hepatobiliary disorders
Hepatitis toxic	1/98 (1%)	1	0/98 (0%)	0
Cholecystitis acute	2/98 (2%)	2	0/98 (0%)	0
Immune system disorders
Behcet's syndrome	0/98 (0%)	0	1/98 (1%)	1
Infections and infestations
Pyelonephritis acute	0/98 (0%)	0	1/98 (1%)	1
Pneumonia	1/98 (1%)	1	0/98 (0%)	0
Pulmonary tuberculosis	1/98 (1%)	1	0/98 (0%)	0
Injury, poisoning and procedural complications
Fall	0/98 (0%)	0	1/98 (1%)	1
Femoral neck fracture	0/98 (0%)	0	1/98 (1%)	1
Musculoskeletal and connective tissue disorders
Muscular weakness	0/98 (0%)	0	1/98 (1%)	1
Nervous system disorders
Intraventricular haemorrhage	1/98 (1%)	1	0/98 (0%)	0
Convulsion	0/98 (0%)	0	2/98 (2%)	2
Renal and urinary disorders
Renal failure	1/98 (1%)	1	0/98 (0%)	0
Other (Not Including Serious) Adverse Events
	Meditoxin®		Botox®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/98 (35.7%)		35/98 (35.7%)
Gastrointestinal disorders
Diarrhoea	3/98 (3.1%)	4	2/98 (2%)	2
Vomiting	3/98 (3.1%)	4	1/98 (1%)	1
Abdominal distension	2/98 (2%)	2	0/98 (0%)	0
Dyspepsia	2/98 (2%)	2	1/98 (1%)	1
Nausea	2/98 (2%)	2	0/98 (0%)	0
Consitipation	1/98 (1%)	1	3/98 (3.1%)	3
General disorders
Oedema peripheral	3/98 (3.1%)	3	1/98 (1%)	1
Injection site haematoma	2/98 (2%)	2	1/98 (1%)	1
Pyrexia	2/98 (2%)	2	2/98 (2%)	2
Hepatobiliary disorders
Cholecystitis acute	2/98 (2%)	2	0/98 (0%)	0
Infections and infestations
Nasopharyngitis	4/98 (4.1%)	5	4/98 (4.1%)	4
Upper respiratory tract infection	2/98 (2%)	2	5/98 (5.1%)	6
Metabolism and nutrition disorders
Hyperlipidaemia	0/98 (0%)	0	2/98 (2%)	2
Musculoskeletal and connective tissue disorders
Pain in extremity	4/98 (4.1%)	5	0/98 (0%)	0
Back pain	3/98 (3.1%)	3	0/98 (0%)	0
Musculoskeletal pain	2/98 (2%)	2	0/98 (0%)	0
Nervous system disorders
Convulsion	1/98 (1%)	1	3/98 (3.1%)	5
Dizziness	1/98 (1%)	1	3/98 (3.1%)	4
Headache	1/98 (1%)	1	3/98 (3.1%)	3
Partial seizures	0/98 (0%)	0	2/98 (2%)	2
Respiratory, thoracic and mediastinal disorders
Cough	0/98 (0%)	0	2/98 (2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All the results which arise directly or indirectly from the clinical trial in any form shall be the exclusive property of the sponsor. PIs and the sponsor will discuss, prior to public release of the results, any draft publication or communication made by the investigator. PIs shall not mention any information for a patent or for any intellectual property rights. The sponsor may use or explit all the results at its own discretion, without any limitation to its property right.