Study Of GSK1358820 In Patients With Post-Stroke Upper Li... | NCT00460564

NCT00460564

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
GSK1358820	Drug	botulinum toxin type A	High-Dose BTX Low-Dose BTX

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.

Eligibility Module

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).

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Fukuoka		811-0213	Japan
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
20569068	Derived	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.

Arm/Group Information

ID	Title	Description
FG000	High-Dose BTX	BTX (GSK1358820) 200U (4 mL) was injected into the wrist and finger muscles, and 40U (0.8 mL) into the thumb muscles if thumb spasticity was present in the 12-week double-blind phase (DB) (once at Week 0)
FG001	High-Dose Placebo	Placebo 4 mL was injected into the wrist and finger muscles, and 0.8 mL into the thumb muscles if thumb spasticity was present in the 12-week double-blind phase (DB) (once at Week 0)
FG002	Low-Dose BTX	BTX (GSK1358820) 120U (2.4 mL) was injected into the wrist and finger muscles, and 30U (0.6 mL) into the thumb muscles if thumb spasticity was present in double-blind phase in the 12-week (DB) (once at Week 0)
FG003	Low-Dose Placebo	Placebo 2.4 mL was injected into the wrist and finger muscles, and 0.6 mL into the thumb muscles if thumb spasticity was present in the 12-week double-blind phase (DB) (once at Week 0)
FG004	DB High-Dose BTX + OL High-Dose BTX	BTX (GSK1358820) 200U (4 mL) was injected into the wrist and finger muscles, and 40U (0.8 mL) into the thumb muscles if thumb spasticity was present in the 12-week double-blind phase (DB) (once at Week 0) plus the 36-week open-label phase (OL) following the DB phase (up to 3 times, from Week 12 to Week 36 if participant met re-injection criteria [Modified Ashworth Scale (MAS) score of wrist >=2 and at least 12 weeks (84 days) since the last injection])
FG005	DB High-Dose Placebo + OL High-Dose BTX	Placebo 4 mL was injected into the wrist and finger muscles, and 0.8 mL into the thumb muscles if thumb spasticity was present in the 12-week double-blind phase (DB) (once at Week 0) plus high-dose BTX in open-label phase (OL) following the DB phase (up to 3 times, from Week 12 to Week 36 if participant met re-injection criteria [Modified Ashworth Scale (MAS) score of wrist >=2 and at least 12 weeks (84 days) since the last injection])
FG006	DB Low-Dose BTX + OL High-Dose BTX	BTX (GSK1358820) 120U (2.4 mL) was injected into the wrist and finger muscles, and 30U (0.6 mL) into the thumb muscles if thumb spasticity was present in double-blind phase in the 12-week (DB) (once at Week 0) plus high-dose BTX in open-label phase (OL) following the DB phase (up to 3 times, from Week 12 to Week 36 if participant met re-injection criteria [Modified Ashworth Scale (MAS) score of wrist >=2 and at least 12 weeks (84 days) since the last injection])
FG007	DB Low-Dose Placebo + OL High-Dose BTX	Placebo 2.4 mL was injected into the wrist and finger muscles, and 0.6 mL into the thumb muscles if thumb spasticity was present in the 12-week double-blind phase (DB) (once at Week 0) plus high-dose BTX in open-label phase (OL) following the DB phase (up to 3 times, from Week 12 to Week 36 if participant met re-injection criteria [Modified Ashworth Scale (MAS) score of wrist >=2 and at least 12 weeks (84 days) since the last injection])

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	High-Dose BTX	BTX (GSK1358820) 200U (4 mL) was injected into the wrist and finger muscles, and 40U (0.8 mL) into the thumb muscles if thumb spasticity was present in the 12-week double-blind phase (DB) (once at Week 0)
BG001	High-Dose Placebo

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS wrist score

Posted

Mean

Standard Deviation

Score*week

Baseline, Week 12

ID	Title	Description
OG000

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	High-Dose BTX	BTX (GSK1358820) 200U (4 mL) was injected into the wrist and finger muscles, and 40U (0.8 mL) into the thumb muscles if thumb spasticity was present in the 12-week double-blind phase (DB) (once at Week 0)

ID	Term
D020521	Stroke
D009128	Muscle Spasticity

ID	Term
D002561	Cerebrovascular Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases