Clinical trial NCT00460655: Study of GSK1358820 In Patients With Post-Stroke Lower Limb Spasticity
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-Stroke Spasticity
Cerebrovascular Accident
Keywords: Post-Stroke
Lower Limb
botulinum toxin type A
Spasticity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-04-16
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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).

Primary outcomes:
measure: 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)
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase
timeFrame: Baseline; Weeks 1, 4, 6, 8, and 12
measure: Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase
timeFrame: Baseline; Weeks 1, 4, 6, 8, and 12
measure: Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase
timeFrame: Baseline; Weeks 1, 4, 6, 8, and 12
measure: 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
timeFrame: Baseline; Weeks 1, 4, 6, 8, and 12
measure: 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
timeFrame: Baseline; Weeks 1, 4, 6, 8, and 12
measure: 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
timeFrame: Baseline; Weeks 1, 4, 6, 8, and 12
measure: 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
timeFrame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
measure: 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
timeFrame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
measure: 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
timeFrame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
measure: 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
timeFrame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
measure: 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
timeFrame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
measure: 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
timeFrame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Yamaguchi
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kaji R, Osako Y, Suyama K, Maeda T, Uechi Y, Iwasaki M; GSK1358820 Spasticity Study Group. Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial. J Neurol. 2010 Aug;257(8):1330-7. doi: 10.1007/s00415-010-5526-3. Epub 2010 Apr 1.