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

• ClinicalTrials.gov Identifier: NCT01313767
• Recruitment Status: Completed
• First Posted: March 14, 2011
• Results First Posted: March 29, 2019
• Last Update Posted: March 29, 2019
• Sponsor: Medy-Tox
• Information provided by (Responsible Party): Medy-Tox

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 (Clinical Trial)
• 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: March 2011
• Actual Primary Completion Date: January 2012
• Actual Study Completion Date: February 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. MAS(Modified Ashworth Scale) of Wrist Flexor [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: week 12 ]
    Global assessment evaluated by investigator at week 12 after injection
14. Global Assessment by Patient or Caregiver [ Time Frame: week 12 ]
    Global assessment evaluated by patient or caregiver at week 12 after injection
15. Carer Burden Scale of Cleaning the Palm [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

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

Criteria

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.

Contacts and Locations

Locations

Korea, Republic of

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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

Keywords provided by Medy-Tox:

spasticity; upperlimb; Botulinum toxin

Additional relevant MeSH terms:

Muscle Spasticity; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents