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Study Of GSK1358820 In Patients With Post-Stroke Upper Limb Spasticity

Primary Purpose

Post-Stroke Spasticity, Cerebrovascular Accident

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
GSK1358820
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post-Stroke Spasticity focused on measuring Spasticity, Post-Stroke, botulinum toxin type A, Upper Limb

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects eligible for enrollment in the study must meet all of the following criteria:

  • Patients with upper limb spasticity who are at least 6 months post stroke and present with spasticity of both the wrist and fingers at the start of double-blind phase (Visit 2).
  • Wrist flexor muscle tone of ≥3 and finger flexor muscle tone of ≥2 on the MAS, and at least one functional disability item (i.e., hygiene, pain, dressing or limb posture) with a rating of ≥2 on the Disabilty Assessment Scale (DAS) 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.
  • ≥40kg 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.
  • 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 wrist and/or fingers (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 wrist and/or finger spasticity.
  • Casting of the study upper 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 botulinum toxin therapy.
  • 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, hepatic or respiratory disease.
  • Infection or dermatological condition at the proposed injection sites.
  • Previous or planned participation in another clinical study (including the lower 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).

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

High-Dose BTX

High-Dose Placebo

Low-Dose BTX

Low-Dose Placebo

Arm Description

Outcomes

Primary Outcome Measures

Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Wrist Score to the End of the DB Phase (Week 12) in the High-dose Groups
Change from baseline in MAS wrist 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 wrist score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS wrist score. Negative changes from baseline indicate improvement, and the AUC has a negative sign.

Secondary Outcome Measures

Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Wrist Score to the End of the DB Phase (Week 12) in the Low-dose Groups
Change from baseline in MAS wrist 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 (HA) and changes from baseline on the vertical axis, the area surrounded by the MAS wrist score change curve and the HA was calculated and used as a summary index (AUC) for assessment of the MAS wrist score. Negative changes from baseline indicate improvement, and the area under the AUC has a negative sign.
Mean Change From Baseline in MAS Wrist Score From Baseline to Week 12 of the Double-blind Phase
The investigator assessed MAS wrist 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 MAS Finger Score From Baseline to Week 12 of the Double-blind Phase
The investigator assessed MAS finger 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 Disability Assessment Scale (DAS) Score of Principal Measure From Baseline to Week 12 of the Double-blind Phase
DAS scores of Hygiene, Pain, Dressing, and Limb posture were assessed using a 4-point scale (0=No functional disability to 3=Severe disability). Prior to the first injection, the investigator, in consultation with the participant, selected one functional disability item and assessed it as a principal measure at each time point in the double-blind phase.
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Hygiene From Baseline to week12 of the Double-blind Phase
DAS score of Hygiene was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point in double-blind phase.
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Pain From Baseline to Week 12 of the Double-blind Phase
DAS score of pain was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point in the double-blind phase.
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Dressing From Baseline to Week 12 of the Double-blind Phase
DAS score of Dressing was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point in the double-blind phase.
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Limb Posture From Baseline to Week 12 of the Double-blind Phase
DAS score of Limb Posture was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point in the double-blind phase.
Mean Change From Baseline in Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase
The CGI score 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 Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase
The CGI score 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 Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase
The CGI score 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 Wrist Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The investigator assessed the MAS wrist 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 MAS Finger Score From at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The investigator assessed the MAS finger 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 Disability Assessment Scale (DAS) Score of Principal Measure at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
DAS scores of Hygiene, Pain, Dressing, and Limb posture were assessed using a 4-point scale (0=No functional disability to 3=Severe disability). Prior to the first injection, the investigator, in consultation with the participant, selected one functional disability item and assessed it as a principal measure 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 Disability Assessment Scale (DAS) Score of Hygiene at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The DAS score of Hygiene was assessed using a 4-point scale (0=No functional disability; 3=Severe disability) at each time point from baseline (at the start of the double-blind phase) to Week 48. BTX was injected in participants up to 3 times from Week 12 to Week 36 when participants met re-injection criteria. Measurements were taken at each point until Week 48 and summarized by the number of weeks after the re-injection in individuals (4, 8, and 12 weeks after each injection) in open-label phase; thus, measurements could have been taken up to Week 48 (12 weeks after the Week 36 injection).
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Disability Assessment Scale (DAS) Score of Pain at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The DAS score of Pain was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point from baseline (at the start of the double-blind phase) to Week 48. BTX was injected in participants up to 3 times from Week 12 to Week 36 when participants met re-injection criteria. Measurements were taken at each point until Week 48 and summarized by the number of weeks after the re-injection in individuals (4, 8, and 12 weeks after each injection) in open-label phase; thus, measurements could have been taken up to Week 48 (12 weeks after the Week 36 injection).
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Disability Assessment Scale (DAS) Score of Dressing at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The DAS score of Dressing was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point from baseline (at the start of the double-blind phase) to Week 48. BTX was injected in participants up to 3 times from Week 12 to Week 36 when participants met re-injection criteria. Measurements were taken at each point until Week 48 and summarized by the number of weeks after the re-injection in individuals (4, 8, and 12 weeks after each injection) in open-label phase; thus, measurements could have been taken up to Week 48 (12 weeks after the Week 36 injection).
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Disability Assessment Scale (DAS) Score of Limb Posture at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The DAS score of Limb Posture was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point from baseline (at the start of the double-blind phase) to Week 48. BTX was injected in participants up to 3 times from Weeks 12 to 36 when participants met re-injection criteria. Measurements were taken at each point until Week 48 and summarized by the number of weeks after the re-injection in individuals (4, 8, and 12 weeks after each injection) in open-label phase; thus, measurements could have been taken up to Week 48 (12 weeks after the Week 36 injection).
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
The CGI score 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
The CGI score 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
The CGI score 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.

Full Information

First Posted
April 13, 2007
Last Updated
May 25, 2017
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00460564
Brief Title
Study Of GSK1358820 In Patients With Post-Stroke Upper Limb Spasticity
Official Title
A Multicenter Study to Evaluate the Efficacy and Safety in Patients With Post-Stroke Upper Limb Spasticity Receiving a Double-Blind, Placebo-Controlled GSK1358820 Treatment Followed by an Open-Label GSK1358820 Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
May 2007 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a study to confirm the superior efficacy of a single treatment of GSK1358820 over placebo in patients with post-stroke upper limb spasticity of both the wrist and finger flexors using the Modified Ashworth Scale (MAS) wrist score.
Detailed Description
This is a study to confirm the superior efficacy of a single treatment of GSK1358820 over placebo in patients with post-stroke upper limb spasticity of both the wrist and finger flexors using the Modified Ashworth Scale (MAS) wrist score.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-Stroke Spasticity, Cerebrovascular Accident
Keywords
Spasticity, Post-Stroke, botulinum toxin type A, Upper Limb

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
109 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High-Dose BTX
Arm Type
Active Comparator
Arm Title
High-Dose Placebo
Arm Type
Placebo Comparator
Arm Title
Low-Dose BTX
Arm Type
Active Comparator
Arm Title
Low-Dose Placebo
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
GSK1358820
Intervention Description
botulinum toxin type A
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Wrist Score to the End of the DB Phase (Week 12) in the High-dose Groups
Description
Change from baseline in MAS wrist 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 wrist score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS wrist score. Negative changes from baseline indicate improvement, and the AUC has a negative sign.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Wrist Score to the End of the DB Phase (Week 12) in the Low-dose Groups
Description
Change from baseline in MAS wrist 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 (HA) and changes from baseline on the vertical axis, the area surrounded by the MAS wrist score change curve and the HA was calculated and used as a summary index (AUC) for assessment of the MAS wrist score. Negative changes from baseline indicate improvement, and the area under the AUC has a negative sign.
Time Frame
Baseline, Week 12
Title
Mean Change From Baseline in MAS Wrist Score From Baseline to Week 12 of the Double-blind Phase
Description
The investigator assessed MAS wrist 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.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in MAS Finger Score From Baseline to Week 12 of the Double-blind Phase
Description
The investigator assessed MAS finger 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.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Principal Measure From Baseline to Week 12 of the Double-blind Phase
Description
DAS scores of Hygiene, Pain, Dressing, and Limb posture were assessed using a 4-point scale (0=No functional disability to 3=Severe disability). Prior to the first injection, the investigator, in consultation with the participant, selected one functional disability item and assessed it as a principal measure at each time point in the double-blind phase.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Hygiene From Baseline to week12 of the Double-blind Phase
Description
DAS score of Hygiene was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point in double-blind phase.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Pain From Baseline to Week 12 of the Double-blind Phase
Description
DAS score of pain was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point in the double-blind phase.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Dressing From Baseline to Week 12 of the Double-blind Phase
Description
DAS score of Dressing was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point in the double-blind phase.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Limb Posture From Baseline to Week 12 of the Double-blind Phase
Description
DAS score of Limb Posture was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point in the double-blind phase.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase
Description
The CGI score 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.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase
Description
The CGI score 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.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline in Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase
Description
The CGI score 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.
Time Frame
Baseline; Weeks 1, 4, 6, 8, and 12
Title
Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Wrist Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
Description
The investigator assessed the MAS wrist 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.
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Finger Score From at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
Description
The investigator assessed the MAS finger 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.
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Disability Assessment Scale (DAS) Score of Principal Measure at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
Description
DAS scores of Hygiene, Pain, Dressing, and Limb posture were assessed using a 4-point scale (0=No functional disability to 3=Severe disability). Prior to the first injection, the investigator, in consultation with the participant, selected one functional disability item and assessed it as a principal measure at each time point from baseline (at the start of the double-blind phase) to Week 48.
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Disability Assessment Scale (DAS) Score of Hygiene at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
Description
The DAS score of Hygiene was assessed using a 4-point scale (0=No functional disability; 3=Severe disability) at each time point from baseline (at the start of the double-blind phase) to Week 48. BTX was injected in participants up to 3 times from Week 12 to Week 36 when participants met re-injection criteria. Measurements were taken at each point until Week 48 and summarized by the number of weeks after the re-injection in individuals (4, 8, and 12 weeks after each injection) in open-label phase; thus, measurements could have been taken up to Week 48 (12 weeks after the Week 36 injection).
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Disability Assessment Scale (DAS) Score of Pain at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
Description
The DAS score of Pain was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point from baseline (at the start of the double-blind phase) to Week 48. BTX was injected in participants up to 3 times from Week 12 to Week 36 when participants met re-injection criteria. Measurements were taken at each point until Week 48 and summarized by the number of weeks after the re-injection in individuals (4, 8, and 12 weeks after each injection) in open-label phase; thus, measurements could have been taken up to Week 48 (12 weeks after the Week 36 injection).
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Disability Assessment Scale (DAS) Score of Dressing at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
Description
The DAS score of Dressing was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point from baseline (at the start of the double-blind phase) to Week 48. BTX was injected in participants up to 3 times from Week 12 to Week 36 when participants met re-injection criteria. Measurements were taken at each point until Week 48 and summarized by the number of weeks after the re-injection in individuals (4, 8, and 12 weeks after each injection) in open-label phase; thus, measurements could have been taken up to Week 48 (12 weeks after the Week 36 injection).
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Disability Assessment Scale (DAS) Score of Limb Posture at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
Description
The DAS score of Limb Posture was assessed using a 4-point scale (0=No functional disability to 3=Severe disability) at each time point from baseline (at the start of the double-blind phase) to Week 48. BTX was injected in participants up to 3 times from Weeks 12 to 36 when participants met re-injection criteria. Measurements were taken at each point until Week 48 and summarized by the number of weeks after the re-injection in individuals (4, 8, and 12 weeks after each injection) in open-label phase; thus, measurements could have been taken up to Week 48 (12 weeks after the Week 36 injection).
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
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
Description
The CGI score 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.
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
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
Description
The CGI score 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.
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Title
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
Description
The CGI score 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.
Time Frame
Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects eligible for enrollment in the study must meet all of the following criteria: Patients with upper limb spasticity who are at least 6 months post stroke and present with spasticity of both the wrist and fingers at the start of double-blind phase (Visit 2). Wrist flexor muscle tone of ≥3 and finger flexor muscle tone of ≥2 on the MAS, and at least one functional disability item (i.e., hygiene, pain, dressing or limb posture) with a rating of ≥2 on the Disabilty Assessment Scale (DAS) 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. ≥40kg 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. 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 wrist and/or fingers (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 wrist and/or finger spasticity. Casting of the study upper 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 botulinum toxin therapy. 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, hepatic or respiratory disease. Infection or dermatological condition at the proposed injection sites. Previous or planned participation in another clinical study (including the lower 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Fukuoka
ZIP/Postal Code
811-0213
Country
Japan
Facility Name
GSK Investigational Site
City
Hiroshima
ZIP/Postal Code
720-0825
Country
Japan
Facility Name
GSK Investigational Site
City
Hiroshima
ZIP/Postal Code
728-0001
Country
Japan
Facility Name
GSK Investigational Site
City
Hokkaido
ZIP/Postal Code
005-0802
Country
Japan
Facility Name
GSK Investigational Site
City
Hokkaido
ZIP/Postal Code
006-0805
Country
Japan
Facility Name
GSK Investigational Site
City
Hokkaido
ZIP/Postal Code
053-0803
Country
Japan
Facility Name
GSK Investigational Site
City
Ibaraki
ZIP/Postal Code
302-0112
Country
Japan
Facility Name
GSK Investigational Site
City
Kanagawa
ZIP/Postal Code
227-8518
Country
Japan
Facility Name
GSK Investigational Site
City
Kanagawa
ZIP/Postal Code
247-8533
Country
Japan
Facility Name
GSK Investigational Site
City
Kanagawa
ZIP/Postal Code
253-8558
Country
Japan
Facility Name
GSK Investigational Site
City
Kanagawa
ZIP/Postal Code
257-0001
Country
Japan
Facility Name
GSK Investigational Site
City
Kumamoto
ZIP/Postal Code
860-8518
Country
Japan
Facility Name
GSK Investigational Site
City
Shizuoka
ZIP/Postal Code
410-1128
Country
Japan
Facility Name
GSK Investigational Site
City
Shizuoka
ZIP/Postal Code
410-2507
Country
Japan
Facility Name
GSK Investigational Site
City
Shizuoka
ZIP/Postal Code
410-3293
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
105-8471
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
142-8666
Country
Japan
Facility Name
GSK Investigational Site
City
Yamaguchi
ZIP/Postal Code
740-0021
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
20569068
Citation
Kaji R, Osako Y, Suyama K, Maeda T, Uechi Y, Iwasaki M; GSK1358820 Spasticity Study Group. Botulinum toxin type A in post-stroke upper limb spasticity. Curr Med Res Opin. 2010 Aug;26(8):1983-92. doi: 10.1185/03007995.2010.497103.
Results Reference
derived

Learn more about this trial

Study Of GSK1358820 In Patients With Post-Stroke Upper Limb Spasticity

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