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

NCT00460564 | Completed Phase 3 Results

• 1 other identifier: BTX108509
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 18

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.

Conditions

Post-Stroke Spasticity; Cerebrovascular Accident

Keywords

Spasticity; Post-Stroke; botulinum toxin type A; Upper Limb

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Week 12

Secondary Outcomes (21)

• 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

  Baseline, Week 12

• Mean Change From Baseline in MAS Wrist Score From Baseline to Week 12 of the Double-blind Phase

  Baseline; Weeks 1, 4, 6, 8, and 12

• Mean Change From Baseline in MAS Finger Score From Baseline to Week 12 of the Double-blind Phase

  Baseline; Weeks 1, 4, 6, 8, and 12

• Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Principal Measure From Baseline to Week 12 of the Double-blind Phase

  Baseline; Weeks 1, 4, 6, 8, and 12

• Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Hygiene From Baseline to week12 of the Double-blind Phase

  Baseline; Weeks 1, 4, 6, 8, and 12

Study Arms (4)

High-Dose BTX

ACTIVE COMPARATOR

Drug: GSK1358820

High-Dose Placebo

PLACEBO COMPARATOR

Drug: Placebo

Low-Dose BTX

ACTIVE COMPARATOR

Drug: GSK1358820

Low-Dose Placebo

ACTIVE COMPARATOR

Drug: Placebo

Interventions

GSK1358820 DRUG

botulinum toxin type A

High-Dose BTX; Low-Dose BTX

Placebo DRUG

Placebo

High-Dose Placebo; Low-Dose Placebo

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (18)

GSK Investigational Site

Fukuoka, 811-0213, Japan

Location

GSK Investigational Site

Hiroshima, 720-0825, Japan

Location

GSK Investigational Site

Hiroshima, 728-0001, Japan

Location

GSK Investigational Site

Hokkaido, 005-0802, Japan

Location

GSK Investigational Site

Hokkaido, 006-0805, Japan

Location

GSK Investigational Site

Hokkaido, 053-0803, Japan

Location

GSK Investigational Site

Ibaraki, 302-0112, Japan

Location

GSK Investigational Site

Kanagawa, 227-8518, Japan

Location

GSK Investigational Site

Kanagawa, 247-8533, Japan

Location

GSK Investigational Site

Kanagawa, 253-8558, Japan

Location

GSK Investigational Site

Kanagawa, 257-0001, Japan

Location

GSK Investigational Site

Kumamoto, 860-8518, Japan

Location

GSK Investigational Site

Shizuoka, 410-1128, Japan

Location

GSK Investigational Site

Shizuoka, 410-2507, Japan

Location

GSK Investigational Site

Shizuoka, 410-3293, Japan

Location

GSK Investigational Site

Tokyo, 105-8471, Japan

Location

GSK Investigational Site

Tokyo, 142-8666, Japan

Location

GSK Investigational Site

Yamaguchi, 740-0021, Japan

Location

Related Publications (1)

• 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.

  PMID: 20569068 DERIVED

MeSH Terms

Conditions

Stroke; Muscle Spasticity

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The frequency threshold (5%) for reporting other adverse events is based on the result of the double-blind phase for the first four arms listed in the table and on the open-label phase for the last four arms listed in the table.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2007
• First Posted: April 16, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: May 30, 2017
• Results First Posted: February 10, 2010

Record last verified: 2017-05

Locations

JP (18)