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

This study has been completed.

Sponsor:

Information provided by:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00460564

First received: April 13, 2007

Last updated: March 17, 2011

Last verified: March 2011

History of Changes

Results First Received: September 2, 2009

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
Conditions:	Post-Stroke Spasticity Cerebrovascular Accident
Interventions:	Drug: GSK1358820 Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
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)
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)
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)
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)
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])
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])
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])
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])

Participant Flow for 2 periods

Period 1: Double-Blind Phase (12 Weeks)

	High-Dose BTX	High-Dose Placebo	Low-Dose BTX	Low-Dose Placebo
STARTED	51	26	21	11
COMPLETED	47	25	21	11
NOT COMPLETED	4	1	0	0
Adverse Event	3	1	0	0
Withdrawal by Subject	1	0	0	0

Period 2: Open-Label Phase (36 Weeks)

	DB High-Dose BTX + OL High-Dose BTX	DB High-Dose Placebo + OL High-Dose BTX	DB Low-Dose BTX + OL High-Dose BTX	DB Low-Dose Placebo + OL High-Dose BTX
STARTED	47	25	21	11
COMPLETED	38	19	19	11
NOT COMPLETED	9	6	2	0
Adverse Event	3	5	2	0
Withdrawal by Subject	5	1	0	0
Concentrate on Treatment of Diabetes	1	0	0	0

Baseline Characteristics

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Reporting Groups

	Description
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)
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)
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)
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)
Total	Total of all reporting groups

Baseline Measures

	High-Dose BTX	High-Dose Placebo	Low-Dose BTX	Low-Dose Placebo	Total
Number of Participants [units: participants]	51	26	21	11	109
Age [units: years] Mean ± Standard Deviation	63.5 ± 9.32	63.6 ± 11.03	62.7 ± 9.74	62.3 ± 9.61	63.2 ± 9.73
Gender [units: participants]
Female	15	12	2	6	35
Male	36	14	19	5	74
Race/Ethnicity, Customized [units: participants]
Asian-Japanese	51	26	21	11	109

Outcome Measures

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1. 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 [ Time Frame: Baseline, Week 12 ]

Show Outcome Measure 1

2. Secondary:

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 [ Time Frame: Baseline, Week 12 ]

Show Outcome Measure 2

3. Secondary:

Mean Change From Baseline in MAS Wrist Score From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 3

4. Secondary:

Mean Change From Baseline in MAS Finger Score From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

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Measure Type	Secondary
Measure Title	Mean Change From Baseline in MAS Finger Score From Baseline to Week 12 of the Double-blind Phase
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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)
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)
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)
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)

Measured Values

	High-Dose BTX	High-Dose Placebo	Low-Dose BTX	Low-Dose Placebo
Number of Participants Analyzed [units: participants]	51	26	21	11
Mean Change From Baseline in MAS Finger Score From Baseline to Week 12 of the Double-blind Phase [units: Points on a scale] Mean ± Standard Deviation
Week 1	-0.60 ± 0.671	-0.19 ± 0.402	-0.69 ± 0.733	-0.23 ± 0.684
Week 4	-0.92 ± 0.821	-0.37 ± 0.657	-0.95 ± 0.757	-0.55 ± 0.688
Week 6	-0.97 ± 0.800	-0.33 ± 0.734	-0.98 ± 0.782	-0.23 ± 0.684
Week 8	-0.86 ± 0.790	-0.35 ± 0.759	-0.69 ± 0.750	-0.27 ± 0.518
Week 12	-0.67 ± 0.709	-0.26 ± 0.597	-0.45 ± 0.947	-0.14 ± 0.323

No statistical analysis provided for Mean Change From Baseline in MAS Finger Score From Baseline to Week 12 of the Double-blind Phase

5. Secondary:

Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Principal Measure From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 5

6. Secondary:

Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Hygiene From Baseline to week12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 6

7. Secondary:

Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Pain From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 7

8. Secondary:

Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Dressing From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 8

9. Secondary:

Mean Change From Baseline in Disability Assessment Scale (DAS) Score of Limb Posture From Baseline to Week 12 of the Double-blind Phase [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 9

10. Secondary:

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 [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 10

11. Secondary:

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 [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 11

12. Secondary:

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 [ Time Frame: Baseline; Weeks 1, 4, 6, 8, and 12 ]

Show Outcome Measure 12

13. Secondary:

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 [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ]

Show Outcome Measure 13

14. Secondary:

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 [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ]

Show Outcome Measure 14

15. Secondary:

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 [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ]

Show Outcome Measure 15

16. Secondary:

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 [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ]

Show Outcome Measure 16

17. Secondary:

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 [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ]

Show Outcome Measure 17

18. Secondary:

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 [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ]

Show Outcome Measure 18

19. Secondary:

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 [ Time Frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) ]

Show Outcome Measure 19

20. Secondary:

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) ]

Show Outcome Measure 20

21. Secondary:

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) ]

Show Outcome Measure 21

22. Secondary:

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) ]

Show Outcome Measure 22

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided by GlaxoSmithKline

Publications automatically indexed to this study:

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.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00460564 History of Changes
Other Study ID Numbers:	BTX108509
Study First Received:	April 13, 2007
Results First Received:	September 2, 2009
Last Updated:	March 17, 2011
Health Authority:	Japan: Ministry of Health, Labor and Welfare

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