Study of GSK1358820 In Patients With Post-Stroke Lower Limb Spasticity

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00460655
First received: April 13, 2007
Last updated: August 30, 2010
Last verified: August 2010
  Purpose

This is a study to confirm the superior efficacy of GSK1358820 over placebo in patients with equinus deformity associated with post-stroke lower limb spasticity using the Modified Ashworth Scale (MAS) ankle score.


Condition Intervention Phase
Post-Stroke Spasticity
Cerebrovascular Accident
Drug: GSK1358820
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter Study to Evaluate the Efficacy and Safety in Patients With Post-Stroke Lower Limb Spasticity Receiving a Double-Blind, Placebo-Controlled GSK1358820 Treatment Followed by an Open-Label GSK1358820 Treatment

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Ankle Score to the End of the DB Phase (Week 12) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Change from baseline in MAS ankle score using a 6-point scale (0, 1, 1+ [regarded as 1.5], 2, 3, and 4; 0=no increase in muscle tone; 4=affected part[s] rigid in flexion/extension) to each time point in the DB phase was calculated. In the graph plotting time points on the horizontal axis and changes from baseline on the vertical axis, the area surrounded by the MAS ankle score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS ankle score. Negative changes from baseline indicate improvement, and the AUC has a negative sign.


Secondary Outcome Measures:
  • Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ] [ Designated as safety issue: No ]
    The investigator assessed Modified Ashworth Scale (MAS) ankle score using a 6-point scale (0, 1, 1+, 2, 3, and 4; 0=No increase in muscle tone to 4=Affected part[s] rigid in flexion or extension) at each time point in the double-blind phase. The "+1" (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder [less than half] of ROM [range of motion]) of MAS score is regarded as score 1.5.

  • Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ] [ Designated as safety issue: No ]
    The investigator assessed the PRS of gait pattern consisting of 3 parameters. Affected limb was scored on a scale of -1 (worst) to 9 (best) based on 3 parameters (initial foot contact, foot contact at midstance, gait assistive devices) at each time point in double-blind phase.

  • Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ] [ Designated as safety issue: No ]
    The time (seconds) required to walk 10 meters was measured at each time point in the double-blind phase.

  • Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ] [ Designated as safety issue: No ]
    The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase.

  • Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ] [ Designated as safety issue: No ]
    The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase

  • Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ] [ Designated as safety issue: No ]
    The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase

  • Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ] [ Designated as safety issue: No ]
    The investigator assessed Modified Ashworth Scale (MAS) ankle score using a 6-point scale (0, 1, 1+, 2, 3, and 4; 0=No increase in muscle tone to 4=Affected part[s] rigid in flexion or extension) at each time point from baseline (at the start of the double-blind phase) to Week 48. The "+1" (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder [less than half] of ROM [range of motion]) of MAS score is regarded as score 1.5.

  • Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ] [ Designated as safety issue: No ]
    The investigator assessed the PRS of gait pattern consisting of 3 parameters. Affected limb was scored on a scale of -1 (worst) to 9 (best) based on 3 parameters (initial foot contact, foot contact at midstance, gait assistive devices) at each time point from baseline (at the start of the double-blind phase) to Week 48.

  • Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ] [ Designated as safety issue: No ]
    The time (seconds) required to walk 10 meters was measured at each time point from baseline (at the start of the double-blind phase) to Week 48.

  • Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ] [ Designated as safety issue: No ]
    The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48.

  • Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ] [ Designated as safety issue: No ]
    The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48.

  • Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ] [ Designated as safety issue: No ]
    The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48.


Enrollment: 120
Study Start Date: May 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: BTX Drug: GSK1358820
botulinum toxin type A
Other Name: GSK1358820
Placebo Comparator: Placebo Drug: Placebo
Placebo

Detailed Description:

This is a study to confirm the superior efficacy of GSK1358820 over placebo in patients with equinus deformity associated with post-stroke lower limb spasticity using the Modified Ashworth Scale (MAS) ankle score.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects eligible for enrollment in the study must meet all of the following criteria:
  • Patients with lower limb spasticity who are at least 6 months post-stroke and present with equinus deformity (plantar flexion of the ankle) at the start of double-blind phase (Visit 2).
  • Patients with MAS ankle score of ≥3 at the start of double-blind phase (Visit 2).
  • Male or female between 20 and 80 years of age at the time of informed consent. For males, only those who can practice contraception during the study period are eligible.
  • ≥50kg in weight at the start of double-blind phase (Visit 2).
  • Inpatient or outpatient; however, the hospitalization status must remain unchanged during the double-blind phase. NOTE: Subjects may be hospitalized for ≤10 days after injection during the treatment period.
  • Written informed consent from the subject him/herself. If the subject's signature is not legible, the attendance of a witness is required.

Exclusion Criteria:

  • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
  • Bilateral hemiplegia or quadriplegia.
  • Presence of fixed contractures of the ankle (absence of range of motion).
  • Profound atrophy of the muscles to be injected.
  • Previous surgical intervention, phenol block, ethanol block, or Muscle Afferent Block (MAB) for ankle spasticity.
  • Casting of the study lower limb within 3 months prior to the start of double-blind phase (Visit 2).
  • Current treatment with intrathecal baclofen.
  • Use of peripheral muscle relaxants (dantrolene sodium, suxamethonium chloride, pancuronium bromide, vecuronium bromide, rocuronium bromide).
  • Concurrent use of antibiotics that interfere with neuromuscular transmission, such as aminoglycoside antibiotics (e.g., streptomycin sulfate, kanamycin sulfate, gentamicin sulfate, neomycin sulphate, spectinomycin hydrochloride), polypeptide antibiotics (e.g., polymixin B sulfate), lincomycin antibiotics (e.g., lincomycin hydrochloride, clindamycin), and enviomycin sulfate.
  • Previous or current botulinum toxin therapy of any serotype.
  • Diagnosis of systemic neuromuscular disorders (e.g., myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis).
  • Females who are pregnant, nursing, may be pregnant, or planning a pregnancy during the study period.
  • Known allergy or hypersensitivity to any ingredient of study medication (e.g., human serum albumin).
  • Presence of psychiatric disorder or impairment of intellectual function that may interfere with the subject's ability to give informed consent or the conduct of the study.
  • Bedridden patients.
  • Presence of clinically unstable severe cardiovascular disease.
  • Presence of clinically significant severe renal or hepatic disease.
  • Infection or dermatological condition at the proposed injection sites.
  • Previous or planned participation in another clinical study (including the upper limb spasticity study of GSK1358820) within 6 months prior to the start of double-blind phase (Visit 2).
  • Others whom the investigator or sub investigator considers not eligible for the study.
  • Clinically significant severe reduction of muscle strength.
  • Angle closure glaucoma or its preposition (narrow angle).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00460655

Locations
Japan
GSK Investigational Site
Fukuoka, Japan, 811-0213
GSK Investigational Site
Hiroshima, Japan, 720-0825
GSK Investigational Site
Hiroshima, Japan, 728-0001
GSK Investigational Site
Hokkaido, Japan, 005-8555
GSK Investigational Site
Hokkaido, Japan, 005-0802
GSK Investigational Site
Hokkaido, Japan, 053-0803
GSK Investigational Site
Hokkaido, Japan, 006-0805
GSK Investigational Site
Ibaraki, Japan, 302-0112
GSK Investigational Site
Kanagawa, Japan, 247-8533
GSK Investigational Site
Kanagawa, Japan, 257-0001
GSK Investigational Site
Kanagawa, Japan, 253-8558
GSK Investigational Site
Kanagawa, Japan, 227-8518
GSK Investigational Site
Kumamoto, Japan, 860-8518
GSK Investigational Site
Shizuoka, Japan, 410-3293
GSK Investigational Site
Shizuoka, Japan, 410-1128
GSK Investigational Site
Shizuoka, Japan, 410-2507
GSK Investigational Site
Tokyo, Japan, 140-0001
GSK Investigational Site
Tokyo, Japan, 105-8471
GSK Investigational Site
Tokyo, Japan, 142-8666
GSK Investigational Site
Yamaguchi, Japan, 740-0021
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00460655     History of Changes
Other Study ID Numbers: BTX108512
Study First Received: April 13, 2007
Results First Received: September 2, 2009
Last Updated: August 30, 2010
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
Post-Stroke
Lower Limb
botulinum toxin type A
Spasticity

Additional relevant MeSH terms:
Muscle Spasticity
Cerebral Infarction
Stroke
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Botulinum Toxins, Type A
Botulinum Toxins
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014