Trial Outcomes & Findings for Study of GSK1358820 In Patients With Post-Stroke Lower Limb Spasticity (NCT NCT00460655)

NCT ID: NCT00460655

Last Updated: 2010-09-08

Results Overview

Change from baseline in MAS ankle 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 ankle score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS ankle score. Negative changes from baseline indicate improvement, and the AUC has a negative sign.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 120 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2010-09-08

Participant Flow

Participant milestones

Measure	BTX 300U BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	DB BTX + OL BTX BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles 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 \[Modified Ashworth Scale (MAS) score of ankle \>=2 and at least 12 weeks (84 days) since the last injection\])	DB Placebo + OL BTX Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0) plus BTX (GSK1358820) 300U 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 \[Modified Ashworth Scale (MAS) score of ankle \>=2 and at least 12 weeks (84 days) since the last injection\])
Double-Blind Phase (12 Weeks) STARTED	58	62	0	0
Double-Blind Phase (12 Weeks) COMPLETED	52	61	0	0
Double-Blind Phase (12 Weeks) NOT COMPLETED	6	1	0	0
Open-Label Phase (36 Weeks) STARTED	0	0	52	61
Open-Label Phase (36 Weeks) COMPLETED	0	0	45	52
Open-Label Phase (36 Weeks) NOT COMPLETED	0	0	7	9

Reasons for withdrawal

Measure	BTX 300U BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	DB BTX + OL BTX BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles 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 \[Modified Ashworth Scale (MAS) score of ankle \>=2 and at least 12 weeks (84 days) since the last injection\])	DB Placebo + OL BTX Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0) plus BTX (GSK1358820) 300U 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 \[Modified Ashworth Scale (MAS) score of ankle \>=2 and at least 12 weeks (84 days) since the last injection\])
Double-Blind Phase (12 Weeks) Adverse Event	3	0	0	0
Double-Blind Phase (12 Weeks) Withdrawal by Subject	3	0	0	0
Double-Blind Phase (12 Weeks) Protocol Violation	0	1	0	0
Open-Label Phase (36 Weeks) Adverse Event	0	0	1	6
Open-Label Phase (36 Weeks) Withdrawal by Subject	0	0	6	2
Open-Label Phase (36 Weeks) Meeting the Exclusion Criteria	0	0	0	1

Baseline Characteristics

Study of GSK1358820 In Patients With Post-Stroke Lower Limb Spasticity

Baseline characteristics by cohort

Measure	BTX 300U n=58 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Total n=120 Participants Total of all reporting groups
Age Continuous	62.4 years STANDARD_DEVIATION 8.66 • n=5 Participants	62.5 years STANDARD_DEVIATION 9.32 • n=7 Participants	62.5 years STANDARD_DEVIATION 8.97 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	16 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	46 Participants n=7 Participants	96 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Japanese	58 participants n=5 Participants	62 participants n=7 Participants	120 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: 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 ankle score

Change from baseline in MAS ankle 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 ankle score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS ankle score. Negative changes from baseline indicate improvement, and the AUC has a negative sign.

Outcome measures

Measure	BTX 300U n=58 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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)	-8.513 Score*week Standard Deviation 6.6904	-5.085 Score*week Standard Deviation 6.6496

SECONDARY outcome

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

Population: 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 ankle score

The investigator assessed Modified Ashworth Scale (MAS) ankle 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.

Outcome measures

Measure	BTX 300U n=58 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase Week 1	-0.61 Points on a scale Standard Deviation 0.675	-0.52 Points on a scale Standard Deviation 0.765
Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase Week 4	-0.88 Points on a scale Standard Deviation 0.687	-0.43 Points on a scale Standard Deviation 0.718
Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase Week 6	-0.91 Points on a scale Standard Deviation 0.733	-0.47 Points on a scale Standard Deviation 0.712
Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase Week 8	-0.82 Points on a scale Standard Deviation 0.660	-0.43 Points on a scale Standard Deviation 0.676
Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase Week 12	-0.56 Points on a scale Standard Deviation 0.685	-0.40 Points on a scale Standard Deviation 0.583

SECONDARY outcome

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

Population: 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 ankle score

The investigator assessed the PRS of gait pattern consisting of 3 parameters. Affected limb was scored on a scale of -1 (worst) to 9 (best) based on 3 parameters (initial foot contact, foot contact at midstance, gait assistive devices) at each time point in double-blind phase.

Outcome measures

Measure	BTX 300U n=58 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase Week 1	0.40 Points on a scale Standard Deviation 1.178	0.66 Points on a scale Standard Deviation 1.401
Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase Week 4	0.54 Points on a scale Standard Deviation 1.224	0.63 Points on a scale Standard Deviation 1.449
Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase Week 6	0.46 Points on a scale Standard Deviation 1.190	0.72 Points on a scale Standard Deviation 1.474
Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase Week 8	0.61 Points on a scale Standard Deviation 1.188	0.78 Points on a scale Standard Deviation 1.811
Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase Week 12	0.55 Points on a scale Standard Deviation 1.264	0.58 Points on a scale Standard Deviation 1.565

SECONDARY outcome

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

Population: 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 ankle score

The time (seconds) required to walk 10 meters was measured at each time point in the double-blind phase.

Outcome measures

Measure	BTX 300U n=58 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase Week 1	2.14 seconds Standard Deviation 34.828	-5.02 seconds Standard Deviation 11.436
Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase Week 4	-6.10 seconds Standard Deviation 22.852	-7.37 seconds Standard Deviation 20.782
Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase Week 6	-7.80 seconds Standard Deviation 20.568	-8.48 seconds Standard Deviation 18.075
Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase Week 8	-3.14 seconds Standard Deviation 35.780	-8.19 seconds Standard Deviation 18.633
Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase Week 12	-10.14 seconds Standard Deviation 26.930	-8.53 seconds Standard Deviation 24.710

SECONDARY outcome

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

Population: 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 ankle score

The CGI 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.

Outcome measures

Measure	BTX 300U n=58 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 1	0.82 Points on a scale Standard Deviation 1.283	0.45 Points on a scale Standard Deviation 1.082
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 Week 4	1.09 Points on a scale Standard Deviation 1.254	0.64 Points on a scale Standard Deviation 1.065
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 Week 6	1.21 Points on a scale Standard Deviation 1.558	0.66 Points on a scale Standard Deviation 1.182
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 Week 8	1.13 Points on a scale Standard Deviation 1.318	0.59 Points on a scale Standard Deviation 1.230
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 Week 12	0.81 Points on a scale Standard Deviation 1.302	0.52 Points on a scale Standard Deviation 1.273

SECONDARY outcome

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

Population: 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 ankle score

The CGI 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

Outcome measures

Measure	BTX 300U n=58 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 1	0.49 Points on a scale Standard Deviation 1.477	0.34 Points on a scale Standard Deviation 1.470
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 Week 4	0.75 Points on a scale Standard Deviation 1.575	0.44 Points on a scale Standard Deviation 1.756
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 Week 6	0.82 Points on a scale Standard Deviation 1.850	0.72 Points on a scale Standard Deviation 1.976
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 Week 8	1.00 Points on a scale Standard Deviation 2.028	0.70 Points on a scale Standard Deviation 1.978
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 Week 12	0.49 Points on a scale Standard Deviation 1.527	0.49 Points on a scale Standard Deviation 2.180

SECONDARY outcome

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

Population: 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 ankle score

The CGI 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

Outcome measures

Measure	BTX 300U n=58 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 6	0.82 Points on a scale Standard Deviation 1.550	1.03 Points on a scale Standard Deviation 1.906
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 Week 1	0.63 Points on a scale Standard Deviation 1.190	0.48 Points on a scale Standard Deviation 1.004
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 Week 4	0.64 Points on a scale Standard Deviation 1.271	1.07 Points on a scale Standard Deviation 1.377
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 Week 8	1.04 Points on a scale Standard Deviation 1.780	1.00 Points on a scale Standard Deviation 1.643
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 Week 12	1.02 Points on a scale Standard Deviation 1.337	0.97 Points on a scale Standard Deviation 1.505

SECONDARY outcome

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

Population: 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 ankle score

The investigator assessed Modified Ashworth Scale (MAS) ankle 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.

Outcome measures

Measure	BTX 300U n=50 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=57 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 4 after first injection in OL	-1.37 Points on a scale Standard Deviation 0.660	-1.27 Points on a scale Standard Deviation 0.653
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 Week 8 after first injection in OL	-1.29 Points on a scale Standard Deviation 0.682	-1.33 Points on a scale Standard Deviation 0.590
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 Week 12 after first injection in OL	-1.03 Points on a scale Standard Deviation 0.646	-1.04 Points on a scale Standard Deviation 0.654
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 Week 4 after second injection in OL	-1.55 Points on a scale Standard Deviation 0.706	-1.51 Points on a scale Standard Deviation 0.640
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 Week 8 after second injection in OL	-1.36 Points on a scale Standard Deviation 0.675	-1.43 Points on a scale Standard Deviation 0.554
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 Week 12 after second injection in OL	-1.19 Points on a scale Standard Deviation 0.732	-1.21 Points on a scale Standard Deviation 0.750
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 Week 4 after third injection in OL	-1.48 Points on a scale Standard Deviation 0.750	-1.43 Points on a scale Standard Deviation 0.764
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 Week 8 after third injection in OL	-1.41 Points on a scale Standard Deviation 0.694	-1.43 Points on a scale Standard Deviation 0.556
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 Week 12 after third injection in OL	-1.44 Points on a scale Standard Deviation 0.751	-1.34 Points on a scale Standard Deviation 0.578

SECONDARY outcome

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

Population: 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 ankle score

The investigator assessed the PRS of gait pattern consisting of 3 parameters. Affected limb was scored on a scale of -1 (worst) to 9 (best) based on 3 parameters (initial foot contact, foot contact at midstance, gait assistive devices) at each time point from baseline (at the start of the double-blind phase) to Week 48.

Outcome measures

Measure	BTX 300U n=50 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=57 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 4 after first injection in OL	1.10 Points on a scale Standard Deviation 1.433	1.35 Points on a scale Standard Deviation 1.601
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 Week 8 after first injection in OL	1.17 Points on a scale Standard Deviation 1.494	1.46 Points on a scale Standard Deviation 1.668
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 Week 12 after first injection in OL	0.91 Points on a scale Standard Deviation 1.501	1.15 Points on a scale Standard Deviation 1.638
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 Week 4 after second injection in OL	1.30 Points on a scale Standard Deviation 1.389	1.48 Points on a scale Standard Deviation 1.722
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 Week 8 after second injection in OL	1.33 Points on a scale Standard Deviation 1.569	1.47 Points on a scale Standard Deviation 1.700
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 Week 12 after second injection in OL	1.40 Points on a scale Standard Deviation 1.449	1.29 Points on a scale Standard Deviation 1.842
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 Week 4 after third injection in OL	1.28 Points on a scale Standard Deviation 1.461	1.04 Points on a scale Standard Deviation 1.551
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 Week 8 after third injection in OL	1.33 Points on a scale Standard Deviation 1.494	1.15 Points on a scale Standard Deviation 1.433
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 Week 12 after third injection in OL	1.22 Points on a scale Standard Deviation 1.121	0.96 Points on a scale Standard Deviation 1.344

SECONDARY outcome

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

Population: 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 ankle score

The time (seconds) required to walk 10 meters was measured at each time point from baseline (at the start of the double-blind phase) to Week 48.

Outcome measures

Measure	BTX 300U n=50 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=57 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 4 after first injection in OL	-11.21 seconds Standard Deviation 25.670	-12.09 seconds Standard Deviation 27.148
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 Week 8 after first injection in OL	-11.14 seconds Standard Deviation 27.453	-8.05 seconds Standard Deviation 22.735
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 Week 12 after first injection in OL	-10.50 seconds Standard Deviation 27.726	-9.29 seconds Standard Deviation 21.851
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 Week 4 after second injection in OL	-13.49 seconds Standard Deviation 29.674	-13.05 seconds Standard Deviation 31.241
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 Week 8 after second injection in OL	-8.05 seconds Standard Deviation 45.061	-7.65 seconds Standard Deviation 22.715
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 Week 12 after second injection in OL	-16.31 seconds Standard Deviation 32.613	-13.40 seconds Standard Deviation 29.508
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 Week 4 after third injection in OL	-20.09 seconds Standard Deviation 42.452	-13.42 seconds Standard Deviation 33.205
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 Week 8 after third injection in OL	-15.91 seconds Standard Deviation 43.589	-12.10 seconds Standard Deviation 28.240
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 Week 12 after third injection in OL	-16.37 seconds Standard Deviation 51.482	-13.84 seconds Standard Deviation 29.241

SECONDARY outcome

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

Population: 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 ankle score

The CGI 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.

Outcome measures

Measure	BTX 300U n=50 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=57 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 12 after third injection in OL	2.00 Points on a scale Standard Deviation 1.177	1.68 Points on a scale Standard Deviation 1.416
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 Week 4 after first injection in OL	1.43 Points on a scale Standard Deviation 1.443	1.43 Points on a scale Standard Deviation 1.463
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 Week 8 after first injection in OL	1.40 Points on a scale Standard Deviation 1.393	1.54 Points on a scale Standard Deviation 1.513
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 Week 12 after first injection in OL	1.11 Points on a scale Standard Deviation 1.387	1.21 Points on a scale Standard Deviation 1.589
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 Week 4 after second injection in OL	1.93 Points on a scale Standard Deviation 1.639	2.02 Points on a scale Standard Deviation 1.550
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 Week 8 after second injection in OL	1.70 Points on a scale Standard Deviation 1.670	1.89 Points on a scale Standard Deviation 1.676
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 Week 12 after second injection in OL	1.55 Points on a scale Standard Deviation 1.611	1.52 Points on a scale Standard Deviation 1.683
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 Week 4 after third injection in OL	2.07 Points on a scale Standard Deviation 1.387	1.59 Points on a scale Standard Deviation 1.476
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 Week 8 after third injection in OL	2.04 Points on a scale Standard Deviation 1.224	1.82 Points on a scale Standard Deviation 1.389

SECONDARY outcome

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

Population: 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 ankle score

The CGI 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.

Outcome measures

Measure	BTX 300U n=50 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=57 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 4 after first injection in OL	0.92 Points on a scale Standard Deviation 1.891	1.00 Points on a scale Standard Deviation 2.149
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 Week 12 after third injection in OL	1.33 Points on a scale Standard Deviation 2.557	1.86 Points on a scale Standard Deviation 2.013
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 Week 8 after first injection in OL	0.98 Points on a scale Standard Deviation 2.080	1.04 Points on a scale Standard Deviation 2.215
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 Week 12 after first injection in OL	0.66 Points on a scale Standard Deviation 1.536	1.19 Points on a scale Standard Deviation 2.349
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 Week 4 after second injection in OL	1.26 Points on a scale Standard Deviation 2.205	1.75 Points on a scale Standard Deviation 1.973
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 Week 8 after second injection in OL	1.37 Points on a scale Standard Deviation 2.226	1.67 Points on a scale Standard Deviation 2.119
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 Week 12 after second injection in OL	1.19 Points on a scale Standard Deviation 2.222	1.57 Points on a scale Standard Deviation 2.029
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 Week 4 after third injection in OL	1.62 Points on a scale Standard Deviation 2.305	1.66 Points on a scale Standard Deviation 1.396
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 Week 8 after third injection in OL	1.56 Points on a scale Standard Deviation 2.532	1.86 Points on a scale Standard Deviation 1.715

SECONDARY outcome

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

Population: 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 ankle score

The CGI 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.

Outcome measures

Measure	BTX 300U n=50 Participants BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=57 Participants Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)
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 Week 4 after second injection in OL	1.49 Points on a scale Standard Deviation 1.882	2.00 Points on a scale Standard Deviation 1.798
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 Week 8 after second injection in OL	1.42 Points on a scale Standard Deviation 1.880	1.76 Points on a scale Standard Deviation 1.888
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 Week 4 after first injection in OL	1.14 Points on a scale Standard Deviation 1.708	1.54 Points on a scale Standard Deviation 1.878
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 Week 8 after first injection in OL	1.40 Points on a scale Standard Deviation 1.814	1.54 Points on a scale Standard Deviation 1.768
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 Week 12 after first injection in OL	1.28 Points on a scale Standard Deviation 1.919	1.46 Points on a scale Standard Deviation 1.702
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 Week 12 after second injection in OL	1.57 Points on a scale Standard Deviation 1.965	1.83 Points on a scale Standard Deviation 1.992
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 Week 4 after third injection in OL	1.38 Points on a scale Standard Deviation 1.840	1.62 Points on a scale Standard Deviation 2.145
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 Week 8 after third injection in OL	1.30 Points on a scale Standard Deviation 1.918	1.86 Points on a scale Standard Deviation 2.155
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 Week 12 after third injection in OL	1.59 Points on a scale Standard Deviation 2.438	1.50 Points on a scale Standard Deviation 2.219

Adverse Events

BTX 300U

Serious events: 5 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

DB BTX + OL BTX

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

DB Placebo + OL BTX

Serious events: 8 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	BTX 300U n=58 participants at risk BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 participants at risk Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	DB BTX + OL BTX n=50 participants at risk BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles 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 \[Modified Ashworth Scale (MAS) score of ankle \>=2 and at least 12 weeks (84 days) since the last injection\])	DB Placebo + OL BTX n=57 participants at risk Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0) plus BTX (GSK1358820) 300U 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 \[Modified Ashworth Scale (MAS) score of ankle \>=2 and at least 12 weeks (84 days) since the last injection\])
Cardiac disorders Angina pectoris	3.4% 2/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Gastrointestinal disorders Gastric ulcer hemorrhage	1.7% 1/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Injury, poisoning and procedural complications Fibula fracture	1.7% 1/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Musculoskeletal and connective tissue disorders Myalgia	1.7% 1/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Nervous system disorders Convulsion	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.6% 1/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Nervous system disorders Epilepsy	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	2.0% 1/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Psychiatric disorders Depression	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	2.0% 1/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Psychiatric disorders Mania	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Gastrointestinal disorders Colonic polyp	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Gastrointestinal disorders Gastric polyps	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Infections and infestations Gastroenteritis	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	2.0% 1/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Renal and urinary disorders Calculus ureteric	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.

Other adverse events

Measure	BTX 300U n=58 participants at risk BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	Placebo n=62 participants at risk Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0)	DB BTX + OL BTX n=50 participants at risk BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles 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 \[Modified Ashworth Scale (MAS) score of ankle \>=2 and at least 12 weeks (84 days) since the last injection\])	DB Placebo + OL BTX n=57 participants at risk Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0) plus BTX (GSK1358820) 300U 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 \[Modified Ashworth Scale (MAS) score of ankle \>=2 and at least 12 weeks (84 days) since the last injection\])
Infections and infestations Nasopharyngitis	13.8% 8/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	19.4% 12/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	30.0% 15/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	10.5% 6/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Musculoskeletal and connective tissue disorders Myalgia	3.4% 2/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	3.2% 2/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	6.0% 3/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
General disorders Injection site pain	5.2% 3/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.6% 1/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.8% 1/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Infections and infestations Tinea pedis	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	6.0% 3/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Infections and infestations Urinary tract infection	1.7% 1/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	5.3% 3/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Injury, poisoning and procedural complications Contusion	1.7% 1/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.6% 1/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	10.0% 5/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	7.0% 4/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	2.0% 1/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	5.3% 3/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Musculoskeletal and connective tissue disorders Muscle spasm	1.7% 1/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	6.0% 3/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
Skin and subcutaneous tissue disorders Eczema	3.4% 2/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	1.6% 1/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	6.0% 3/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	5.3% 3/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.
General disorders Pyrexia	0.00% 0/58 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/62 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	6.0% 3/50 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.	0.00% 0/57 • Adverse Events (AEs) were classified by onset time because the study consists of the double-blind (DB) and open-label (OL) phases. AEs in the double-blind (DB) phase (Arms 1-2), AEs occurring after the start (injection) of the DB phase (Week 0), but before the first injection day in the open-label (OL) phase; AEs in the OL phase (Arms 3-4), AEs occurring after the first injection day in the OL phase. SAEs and AEs were analyzed in the Full Analysis Set.

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