Trial Outcomes & Findings for Dysport® Adult Lower Limb Spasticity Study (NCT NCT01249404)

Results Overview

Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM)), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Week 4 is reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

388 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2022-09-28

Participant Flow

The study was designed as a mutlicentre study and included 62 investigational centres in Australia, Belgium, the Czech Republic, France, Hungary, Italy, Poland, Portugal, Russia, Slovakia and the United States. Subjects were screened at 53 centres and in 52 centres subjects were randomised to receive study treatment.

A total of 456 subjects were screened, 388 were enrolled into the study and randomised to 1 of 3 treatment groups.

Participant milestones

Participant milestones
Measure	Dysport® 1000 U Subjects received intramuscular (i.m.) injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Placebo Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Study STARTED	127	129	132
Overall Study COMPLETED	120	121	125
Overall Study NOT COMPLETED	7	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Dysport® 1000 U Subjects received intramuscular (i.m.) injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Placebo Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Study Study treatment not received	0	1	2
Overall Study No MAS Score at baseline and/or Week 4	2	0	2
Overall Study Adverse Event	2	2	2
Overall Study Withdrawal by Subject	2	2	0
Overall Study Botulinum toxin (BTX) in upper limb	1	2	1
Overall Study Non compliance to visit schedule	0	1	0

Baseline Characteristics

Dysport® Adult Lower Limb Spasticity Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dysport® 1000 U n=125 Participants Subjects received i.m.injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Total Title n=381 Participants
Age, Continuous	53.2 years STANDARD_DEVIATION 13.2 • n=5 Participants	53.3 years STANDARD_DEVIATION 12.0 • n=7 Participants	51.4 years STANDARD_DEVIATION 12.9 • n=5 Participants	52.6 years STANDARD_DEVIATION 12.7 • n=4 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	49 Participants n=7 Participants	38 Participants n=5 Participants	125 Participants n=4 Participants
Sex: Female, Male Male	87 Participants n=5 Participants	79 Participants n=7 Participants	90 Participants n=5 Participants	256 Participants n=4 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	13 Participants n=7 Participants	5 Participants n=5 Participants	23 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian or White	116 Participants n=5 Participants	109 Participants n=7 Participants	119 Participants n=5 Participants	344 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	14 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	36 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	111 Participants n=5 Participants	117 Participants n=7 Participants	117 Participants n=5 Participants	345 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4.

Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM)), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Week 4 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline to Week 4 in the MAS Score in the Gastrocnemius-soleus Complex (GSC) (Knee Extended)	-0.5 units on a scale Interval -0.7 to -0.4	-0.6 units on a scale Interval -0.8 to -0.5	-0.8 units on a scale Interval -0.9 to -0.7

SECONDARY outcome

Timeframe: At Week 4

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data at Week 4 are included in the analysis.

An assessment of overall treatment response was conducted at Weeks 4 and 12, and discretionary visits at Weeks 16, 20 and 24 and at end of study by an investigator who had not assessed the MAS. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a 9 point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. The mean PGA score at Week 4 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=124 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=125 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Physician's Global Assesment (PGA) of Treatment Response at Week 4	0.7 units on a scale Interval 0.5 to 0.9	0.9 units on a scale Interval 0.7 to 1.1	0.9 units on a scale Interval 0.7 to 1.1

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data at baseline and Week 4 are included in the analysis.

Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Week 4 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=124 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=127 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline to Week 4 in Comfortable Barefoot Walking Speed	0.05 m/s Interval 0.03 to 0.07	0.05 m/s Interval 0.03 to 0.07	0.04 m/s Interval 0.03 to 0.06

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Weeks 1 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in MAS Score in the GSC (Knee Extended) at Weeks 1 and 12 Week 1	-0.4 units on a scale Interval -0.5 to -0.2	-0.4 units on a scale Interval -0.6 to -0.3	-0.5 units on a scale Interval -0.6 to -0.4
Least Squares Mean Change From Baseline in MAS Score in the GSC (Knee Extended) at Weeks 1 and 12 Week 12	-0.4 units on a scale Interval -0.5 to -0.2	-0.4 units on a scale Interval -0.5 to -0.2	-0.6 units on a scale Interval -0.7 to -0.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Muscle tone in the treated limb was assessed by MAS in the soleus (with the knee flexed) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in MAS Score in the Soleus (Knee Flexed) at Weeks 1, 4 and 12 Week 1	-0.4 units on a scale Interval -0.6 to -0.3	-0.4 units on a scale Interval -0.5 to -0.2	-0.6 units on a scale Interval -0.7 to -0.4
Least Squares Mean Change From Baseline in MAS Score in the Soleus (Knee Flexed) at Weeks 1, 4 and 12 Week 4	-0.4 units on a scale Interval -0.6 to -0.3	-0.7 units on a scale Interval -0.8 to -0.5	-0.8 units on a scale Interval -1.0 to -0.7
Least Squares Mean Change From Baseline in MAS Score in the Soleus (Knee Flexed) at Weeks 1, 4 and 12 Week 12	-0.3 units on a scale Interval -0.4 to -0.1	-0.5 units on a scale Interval -0.7 to -0.4	-0.6 units on a scale Interval -0.7 to -0.4

OTHER_PRE_SPECIFIED outcome

Timeframe: At Week 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data at Week 12 are included in the analysis.

An assessment of overall treatment response was conducted at Weeks 4 and 12, and discretionary visits at Weeks 16, 20 and 24 and at end of study by an investigator who had not assessed the MAS. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a 9 point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. The mean PGA scores at Week 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=122 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=120 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=123 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
PGA of Treatment Response at Week 12	0.5 units on a scale Interval 0.3 to 0.7	0.6 units on a scale Interval 0.4 to 0.7	0.6 units on a scale Interval 0.4 to 0.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Comfortable Barefoot Walking Speed at Weeks 1 and 12 Week 1	0.04 m/s Interval 0.02 to 0.05	0.05 m/s Interval 0.04 to 0.07	0.04 m/s Interval 0.02 to 0.05
Least Squares Mean Change From Baseline in Comfortable Barefoot Walking Speed at Weeks 1 and 12 Week 12	0.05 m/s Interval 0.03 to 0.07	0.07 m/s Interval 0.05 to 0.09	0.06 m/s Interval 0.04 to 0.08

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made with shoes, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 1	0.04 m/s Interval 0.02 to 0.05	0.05 m/s Interval 0.03 to 0.07	0.05 m/s Interval 0.03 to 0.07
Least Squares Mean Change From Baseline in Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 4	0.06 m/s Interval 0.04 to 0.08	0.05 m/s Interval 0.03 to 0.07	0.04 m/s Interval 0.02 to 0.06
Least Squares Mean Change From Baseline in Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 12	0.05 m/s Interval 0.03 to 0.07	0.06 m/s Interval 0.04 to 0.08	0.05 m/s Interval 0.03 to 0.07

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Maximal walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 1	0.05 m/s Interval 0.03 to 0.07	0.06 m/s Interval 0.04 to 0.08	0.05 m/s Interval 0.03 to 0.07
Least Squares Mean Change From Baseline in Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 4	0.05 m/s Interval 0.03 to 0.08	0.07 m/s Interval 0.05 to 0.1	0.04 m/s Interval 0.02 to 0.06
Least Squares Mean Change From Baseline in Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 12	0.06 m/s Interval 0.03 to 0.09	0.09 m/s Interval 0.06 to 0.12	0.06 m/s Interval 0.03 to 0.08

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Maximal walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made with shoes, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 1	0.04 m/s Interval 0.03 to 0.06	0.05 m/s Interval 0.03 to 0.07	0.05 m/s Interval 0.03 to 0.07
Least Squares Mean Change From Baseline in Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 4	0.05 m/s Interval 0.03 to 0.08	0.05 m/s Interval 0.03 to 0.08	0.04 m/s Interval 0.02 to 0.07
Least Squares Mean Change From Baseline in Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 12	0.05 m/s Interval 0.02 to 0.08	0.07 m/s Interval 0.04 to 0.1	0.05 m/s Interval 0.03 to 0.08

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Cadence was assessed during the 10-metre walking speed test at comfortable walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Cadence With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 1	0.04 steps/s Interval 0.01 to 0.07	0.07 steps/s Interval 0.04 to 0.1	0.07 steps/s Interval 0.04 to 0.1
Least Squares Mean Change From Baseline in Cadence With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 4	0.06 steps/s Interval 0.02 to 0.09	0.07 steps/s Interval 0.04 to 0.1	0.06 steps/s Interval 0.03 to 0.1
Least Squares Mean Change From Baseline in Cadence With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 12	0.05 steps/s Interval 0.01 to 0.08	0.09 steps/s Interval 0.05 to 0.12	0.06 steps/s Interval 0.03 to 0.09

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Average step length was assessed during the 10-metre walking speed test at comfortable walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Average Step Length With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 12	0.03 m/step Interval 0.01 to 0.04	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.04
Least Squares Mean Change From Baseline in Average Step Length With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 1	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.03
Least Squares Mean Change From Baseline in Average Step Length With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 Week 4	0.03 m/step Interval 0.02 to 0.04	0.02 m/step Interval 0.01 to 0.03	0.01 m/step Interval 0.0 to 0.02

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Cadence was assessed during the 10-metre walking speed test at comfortable walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Cadence With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 Week 1	0.05 steps/s Interval 0.02 to 0.08	0.10 steps/s Interval 0.07 to 0.13	0.05 steps/s Interval 0.02 to 0.08
Least Squares Mean Change From Baseline in Cadence With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 Week 4	0.06 steps/s Interval 0.02 to 0.09	0.08 steps/s Interval 0.04 to 0.11	0.06 steps/s Interval 0.03 to 0.1
Least Squares Mean Change From Baseline in Cadence With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 Week 12	0.07 steps/s Interval 0.04 to 0.11	0.12 steps/s Interval 0.08 to 0.15	0.08 steps/s Interval 0.05 to 0.12

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Average step length was assessed during the 10-metre walking speed test at comfortable walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Average Step Length With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 Week 1	0.01 m/step Interval 0.0 to 0.02	0.02 m/step Interval 0.01 to 0.02	0.02 m/step Interval 0.01 to 0.02
Least Squares Mean Change From Baseline in Average Step Length With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 Week 4	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.03
Least Squares Mean Change From Baseline in Average Step Length With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 Week 12	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.03

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Cadence was assessed during the 10-metre walking speed test at maximal walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Cadence With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 1	0.04 steps/s Interval 0.01 to 0.08	0.06 steps/s Interval 0.02 to 0.09	0.07 steps/s Interval 0.03 to 0.1
Least Squares Mean Change From Baseline in Cadence With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 4	0.05 steps/s Interval 0.02 to 0.09	0.05 steps/s Interval 0.02 to 0.09	0.05 steps/s Interval 0.02 to 0.09
Least Squares Mean Change From Baseline in Cadence With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 12	0.04 steps/s Interval 0.0 to 0.08	0.08 steps/s Interval 0.04 to 0.12	0.07 steps/s Interval 0.03 to 0.11

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Average step length was assessed during the 10-metre walking speed test at maximal walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Average Step Length With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 1	0.02 m/step Interval 0.01 to 0.04	0.02 m/step Interval 0.0 to 0.03	0.01 m/step Interval 0.0 to 0.03
Least Squares Mean Change From Baseline in Average Step Length With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 4	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.0 to 0.03	0.02 m/step Interval 0.0 to 0.03
Least Squares Mean Change From Baseline in Average Step Length With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 Week 12	0.03 m/step Interval 0.01 to 0.04	0.02 m/step Interval 0.0 to 0.03	0.02 m/step Interval 0.0 to 0.03

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Cadence was assessed during the 10-metre walking speed test at maximal walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Cadence With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 1	0.06 steps/s Interval 0.02 to 0.09	0.07 steps/s Interval 0.04 to 0.11	0.05 steps/s Interval 0.02 to 0.09
Least Squares Mean Change From Baseline in Cadence With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 4	0.07 steps/s Interval 0.03 to 0.1	0.08 steps/s Interval 0.04 to 0.12	0.05 steps/s Interval 0.01 to 0.09
Least Squares Mean Change From Baseline in Cadence With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 12	0.06 steps/s Interval 0.02 to 0.11	0.12 steps/s Interval 0.08 to 0.16	0.08 steps/s Interval 0.03 to 0.12

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Average step length was assessed during the 10-metre walking speed test at maximal walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Average Step Length With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 1	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.01 to 0.03
Least Squares Mean Change From Baseline in Average Step Length With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 4	0.02 m/step Interval 0.0 to 0.03	0.02 m/step Interval 0.01 to 0.04	0.02 m/step Interval 0.0 to 0.03
Least Squares Mean Change From Baseline in Average Step Length With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 Week 12	0.02 m/step Interval 0.01 to 0.04	0.02 m/step Interval 0.01 to 0.03	0.02 m/step Interval 0.0 to 0.03

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

The Tardieu Scale in the GSC was used to assess spasticity with the knee extended. Assessments were made at slow (V1) and fast (V3) speeds of stretch. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest (XV1), either due to subject discomfort or a mechanical resistance. The same movement is repeated at a fast speed to determine the angle of catch and release (XV3). The spasticity angle (X) was calculated as the difference between XV1 and XV3. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 1: Angle of Arrest (XV1)	1.7 Degrees Interval 0.7 to 2.6	2.4 Degrees Interval 1.4 to 3.4	2.3 Degrees Interval 1.3 to 3.3
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 4: Angle of Arrest (XV1)	1.3 Degrees Interval 0.1 to 2.5	0.7 Degrees Interval -0.5 to 1.9	1.4 Degrees Interval 0.2 to 2.6
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 12: Angle of Arrest (XV1)	0.5 Degrees Interval -0.8 to 1.7	0.4 Degrees Interval -0.9 to 1.7	0.4 Degrees Interval -0.9 to 1.6
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 1: Angle of Catch (XV3)	3.2 Degrees Interval 1.9 to 4.5	5.1 Degrees Interval 3.8 to 6.5	5.4 Degrees Interval 4.1 to 6.7
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 4: Angle of Catch (XV3)	3.4 Degrees Interval 1.9 to 4.9	4.8 Degrees Interval 3.3 to 6.3	5.3 Degrees Interval 3.8 to 6.8
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 12: Angle of Catch (XV3)	2.6 Degrees Interval 1.0 to 4.2	3.0 Degrees Interval 1.4 to 4.6	2.9 Degrees Interval 1.3 to 4.5
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 1: Spasticity Angle (X)	-1.7 Degrees Interval -2.8 to -0.5	-2.5 Degrees Interval -3.7 to -1.3	-3.2 Degrees Interval -4.4 to -2.0
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 4: Spasticity Angle (X)	-2.5 Degrees Interval -3.7 to -1.3	-4.0 Degrees Interval -5.2 to -2.8	-4.0 Degrees Interval -5.2 to -2.8
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 12: Spasticity Angle (X)	-2.3 Degrees Interval -3.5 to -1.0	-2.4 Degrees Interval -3.7 to -1.1	-2.8 Degrees Interval -4.0 to -1.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

The Tardieu Scale in the GSC was used to assess spasticity with the knee extended. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 = no resistance throughout passive movement; 1 = slight resistance throughout passive movement; 2 = clear catch at precise angle, interrupting passive movement, followed by release; 3 = fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release; 4 = unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline for spasticity grade at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Spasticity Grade (Y) Week 1	-0.2 units on a scale Interval -0.3 to -0.1	-0.2 units on a scale Interval -0.3 to -0.1	-0.3 units on a scale Interval -0.4 to -0.2
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Spasticity Grade (Y) Week 4	-0.1 units on a scale Interval -0.2 to 0.0	-0.3 units on a scale Interval -0.4 to -0.2	-0.4 units on a scale Interval -0.5 to -0.3
Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Spasticity Grade (Y) Week 12	-0.1 units on a scale Interval -0.2 to 0.0	-0.3 units on a scale Interval -0.4 to -0.2	-0.4 units on a scale Interval -0.5 to -0.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

The Tardieu Scale in the soleus was used to assess spasticity with the knee flexed. Assessments were made at slow (V1) and fast (V3) speeds of stretch. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest (XV1), either due to subject discomfort or a mechanical resistance. The same movement is repeated at a fast speed to determine the angle of catch and release (XV3). The spasticity angle (X) was calculated as the difference between XV1 and XV3. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 12: Angle of Catch (XV3)	2.7 Degrees Interval 1.2 to 4.1	4.0 Degrees Interval 2.5 to 5.4	3.7 Degrees Interval 2.2 to 5.1
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 4: Spasticity Angle (X)	-1.8 Degrees Interval -3.1 to -0.6	-3.6 Degrees Interval -4.9 to -2.4	-4.2 Degrees Interval -5.5 to -3.0
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 1: Angle of Arrest (XV1)	1.4 Degrees Interval 0.4 to 2.3	2.2 Degrees Interval 1.2 to 3.2	1.5 Degrees Interval 0.6 to 2.5
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 4: Angle of Arrest (XV1)	1.3 Degrees Interval 0.2 to 2.4	1.2 Degrees Interval 0.1 to 2.3	1.0 Degrees Interval -0.1 to 2.1
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 12: Angle of Arrest (XV1)	0.0 Degrees Interval -1.0 to 1.1	0.4 Degrees Interval -0.7 to 1.5	0.1 Degrees Interval -1.0 to 1.1
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 1: Angle of Catch (XV3)	2.5 Degrees Interval 0.9 to 4.1	4.1 Degrees Interval 2.5 to 5.8	4.1 Degrees Interval 2.5 to 5.8
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 4: Angle of Catch (XV3)	2.9 Degrees Interval 1.5 to 4.4	5.1 Degrees Interval 3.5 to 6.6	4.9 Degrees Interval 3.4 to 6.4
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 1: Spasticity Angle (X)	-1.3 Degrees Interval -2.6 to -0.1	-1.7 Degrees Interval -3.1 to -0.2	-2.8 Degrees Interval -4.2 to -1.4
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) Week 12: Spasticity Angle (X)	-2.8 Degrees Interval -4.1 to -1.6	-3.3 Degrees Interval -4.6 to -2.1	-3.9 Degrees Interval -5.2 to -2.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

The Tardieu Scale in the soleus was used to assess spasticity with the knee flexed. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 = no resistance throughout passive movement; 1 = slight resistance throughout passive movement; 2 = clear catch at precise angle, interrupting passive movement, followed by release; 3 = fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release; 4 = unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline for spasticity grade at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Spasticity Grade (Y) Week 12	-0.1 units on a scale Interval -0.2 to 0.0	-0.4 units on a scale Interval -0.5 to -0.3	-0.4 units on a scale Interval -0.5 to -0.3
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Spasticity Grade (Y) Week 1	-0.1 units on a scale Interval -0.2 to 0.0	-0.2 units on a scale Interval -0.3 to -0.1	-0.3 units on a scale Interval -0.4 to -0.2
Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Spasticity Grade (Y) Week 4	-0.1 units on a scale Interval -0.2 to 0.0	-0.5 units on a scale Interval -0.6 to -0.3	-0.5 units on a scale Interval -0.6 to -0.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

Range of active dorsiflexion of the ankle joint, both with the knee flexed (90°) and extended (measured by goniometry) was used to assess treatment response. The measurements were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits when needed at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed) Week 1: Knee Extended	1.1 Degrees Interval -0.2 to 2.4	1.7 Degrees Interval 0.4 to 3.0	2.4 Degrees Interval 1.1 to 3.7
Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed) Week 4: Knee Extended	1.6 Degrees Interval -0.1 to 3.2	1.5 Degrees Interval -0.2 to 3.1	3.7 Degrees Interval 2.0 to 5.3
Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed) Week 12: Knee Extended	1.7 Degrees Interval 0.1 to 3.2	1.1 Degrees Interval -0.5 to 2.7	2.0 Degrees Interval 0.5 to 3.6
Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed) Week 1: Knee Flexed	1.9 Degrees Interval 0.5 to 3.3	3.0 Degrees Interval 1.5 to 4.4	2.0 Degrees Interval 0.6 to 3.4
Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed) Week 4: Knee Flexed	2.7 Degrees Interval 1.2 to 4.2	2.9 Degrees Interval 1.4 to 4.5	3.3 Degrees Interval 1.8 to 4.9
Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed) Week 12: Knee Flexed	1.8 Degrees Interval 0.2 to 3.3	2.0 Degrees Interval 0.4 to 3.6	1.4 Degrees Interval -0.1 to 2.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 1, 4 and 12

Population: The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.

The intensity of lower limb pain was evaluated using the Scale of Pain Intensity (SPIN) which provided a pictorial representation of pain in a 6-point graphic scale with the degree of red shading inside a circle representing the intensity of pain. The bottom and top of the scale are anchored by two extremes: 'no pain' (circle with no red shading and scored as 0) and 'pain as bad as it could be' (circle completely red and scored as 5), marked with either verbal or visual cues. The intervening points are represented by red circles increasing proportionally in size. The subject marks the circle that best indicates their pain intensity. The SPIN assessments were obtained prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits when needed at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.	Dysport® 1000 U n=125 Participants Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 Participants Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Least Squares Mean Change From Baseline in Lower Limb Pain at Weeks 1, 4 and 12 Week 1	-0.2 units on a scale Interval -0.3 to 0.0	-0.3 units on a scale Interval -0.4 to -0.1	-0.1 units on a scale Interval -0.3 to 0.0
Least Squares Mean Change From Baseline in Lower Limb Pain at Weeks 1, 4 and 12 Week 4	-0.1 units on a scale Interval -0.3 to 0.1	-0.1 units on a scale Interval -0.3 to -0.1	-0.2 units on a scale Interval -0.4 to 0.0
Least Squares Mean Change From Baseline in Lower Limb Pain at Weeks 1, 4 and 12 Week 12	0.1 units on a scale Interval -0.1 to 0.3	-0.2 units on a scale Interval -0.4 to 0.0	-0.1 units on a scale Interval -0.3 to 0.1

Adverse Events

Dysport® 1000 U

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Dysport® 1500 U

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dysport® 1000 U n=127 participants at risk Subjects received intramuscular (i.m.) injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Dysport® 1500 U n=128 participants at risk Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).	Placebo n=130 participants at risk Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Injury, poisoning and procedural complications Fall	9.4% 12/127 • Number of events 14 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.	6.2% 8/128 • Number of events 9 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.	3.1% 4/130 • Number of events 8 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	5.5% 7/127 • Number of events 7 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.	6.2% 8/128 • Number of events 9 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.	2.3% 3/130 • Number of events 3 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.
Musculoskeletal and connective tissue disorders Muscular weakness	2.4% 3/127 • Number of events 3 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.	5.5% 7/128 • Number of events 8 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.	3.1% 4/130 • Number of events 4 • From baseline up to Week 24 +/- 2 weeks. Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.

Additional Information

Medical Director, Neurology

Ipsen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place