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

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

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).

Study Overview

• Status: Completed
• Conditions: Spasticity
• Intervention / Treatment: Drug: Botulinum toxin type A; Drug: Botulinum Toxin type A

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 Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

10. 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.
11. Patient who are participating in other clinical trials at the screening
12. 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.
13. Patients who are not eligible for this study at the discretion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• Seo HG, Paik NJ, Lee SU, Oh BM, Chun MH, Kwon BS, Bang MS. Neuronox versus BOTOX in the Treatment of Post-Stroke Upper Limb Spasticity: A Multicenter Randomized Controlled Trial. PLoS One. 2015 Jun 1;10(6):e0128633. doi: 10.1371/journal.pone.0128633. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: March 10, 2011
• First Submitted That Met QC Criteria: March 10, 2011
• First Posted (Estimate): March 14, 2011

Study Record Updates

• Last Update Posted (Actual): March 29, 2019
• Last Update Submitted That Met QC Criteria: March 26, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: spasticity; Botulinum toxin; upperlimb
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Muscle Spasticity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: MT-PRT-ST01