Dose-response Relationship of Botullinum Toxin (DWP 450) for Finger Flexor Spasticity

Study Design: Randomized Single Blind Study Objective: To determine the dose relationship of DWP 450 for finger flexor spasticity Subjects: 78 patients with upper extremity spasticity after CVA Inclusion criteria: Patient who have spasticity (MAS greater than 2 in finger flexors) Methods: Patients will be randomly assigned to one of 5 groups. Gp 1: placebo, Gp 2: 15U, Gp 3: 30 U, Gp 4: 50 U, Gp 5: 75 U

Study Overview

• Status: Unknown
• Conditions: Spasticity as Sequela of Stroke
• Intervention / Treatment: Drug: Normal Saline 0.9% 1.2 ml; Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 15 U; Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 30 U; Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 50 U; Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 70 U

Detailed Description

Seventy-eight patients with upper extremity spasticity after cerebrovascular accident will be recruited and randomly assigned to one of 5 groups. The groups are as followings.

Gp 1: placebo group (Normal saline 1.2 ml) Gp 2: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 15 U Gp 3: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 30 U Gp 4: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 50 U Gp 5: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 70 U

According to the group, the injection will be performed to the finger flexor musles (flexor digitorum superficialis and profundus). Outcome measurement will be MAS (Modified ashworth scale), FMA, Wolf Motor Assessment, Cross sectional area measured by Ultrasonography.

Patient evaluation will be conducted 2 weeks, 1 months, 2 months, and 3 months after the injection.

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shi-Uk Lee, MD, PhD; Email: shiuk.lee@gmail.com
• Study Contact Backup: Name: Min Hyung Lee; Email: 0206330@gmail.com

Study Locations

• Korea, Republic of
  • Dong Jak Ku
    • Seoul, Dong Jak Ku, Korea, Republic of, 156-707
      • Recruiting
      • Seoul Metropolitan Government-Seoul National University Boramae Medical Center
      • Contact: Shi-Uk Lee, MD, PhD; Email: shiuk.lee@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• over 6 weeks after stroke onset
• MAS (modified Ashworth scale) greater than 2 in finger flexor

Exclusion Criteria:

• neuromuscular junction disease or motor neuron disease
• phenol or alcohol block for the target limbs within 6 months before screening
• botulinum toxin injection within 3 months before screening
• history or plan for tendon lengthening surgery
• significant contracture ormuscle atrophy at the target joint or muscle
• concurrent treatment with intrathecal baclofen
• hypersensitivity or allergy to study drug or its components
• pregnancy or planned pregnancy, breastfeeding
• abnormal lab findings for alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and serum creatinine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Normal Saline 0.9% 1.2 ml will be injected to finger flexor muscles	Drug: Normal Saline 0.9% 1.2 ml
Experimental: Treatment dose 15; Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 15 U will be injected to finger flexor muscles	Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 15 U; Other Names: Nabota (DWP 450)
Experimental: Treatment dose 30; Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 30 U will be injected to finger flexor muscles	Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 30 U; Other Names: Nabota (DWP 450)
Experimental: Treatment dose 50; Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 50 U will be injected to finger flexor muscles	Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 50 U; Other Names: Nabota (DWP 450)
Experimental: Treatment dose 70; Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 70 U will be injected to finger flexor muscles	Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 70 U; Other Names: Nabota (DWP 450)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MAS (Modified Ashworth Scale)	Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension	baseline
MAS (Modified Ashworth Scale)	Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension	2wks after injection
MAS (Modified Ashworth Scale)	Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension	4wks after injection
MAS (Modified Ashworth Scale)	Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension	8wks after injection
MAS (Modified Ashworth Scale)	Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension	12wks after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ultrasonography	measurement of changes of cross sectional area	baseline
Ultrasonography	measurement of changes of cross sectional area	2wks after injection
Ultrasonography	measurement of changes of cross sectional area	4wks after injection
Ultrasonography	measurement of changes of cross sectional area	8wks after injection
Ultrasonography	measurement of changes of cross sectional area	12wks after injection
Fugl Myer Upper Extremity Assessment	measurement of upper extremity function	baseline
Fugl Myer Upper Extremity Assessment	measurement of upper extremity function	2 wks after injection
Fugl Myer Upper Extremity Assessment	measurement of upper extremity function	4 wks after injection
Fugl Myer Upper Extremity Assessment	measurement of upper extremity function	8 wks after injection
Fugl Myer Upper Extremity Assessment	measurement of upper extremity function	12 wks after injection
Wolf Motor Assessment	measurement of upper extremity function	baseline
Wolf Motor Assessment	measurement of upper extremity function	2 wks after injection
Wolf Motor Assessment	measurement of upper extremity function	4 wks after injection
Wolf Motor Assessment	measurement of upper extremity function	8 wks after injection
Wolf Motor Assessment	measurement of upper extremity function	12 wks after injection

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Daewoong Pharmaceutical Co. LTD.
• Investigators: Study Chair: Shi-Uk Lee, Seoul National University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (Actual): May 7, 2018

Study Record Updates

• Last Update Posted (Actual): May 7, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• 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: 26-2016-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO