Dysport® Adult Lower Limb Spasticity Study

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01249404
• Collaborator: (none)
• Enrollment: 388
• Locations: 62
• Arms: 3
• Duration (Months): 38
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to assess the efficacy of Dysport® compared to placebo in improving muscle tone in hemiparetic subjects with lower limb spasticity due to stroke or traumatic brain injury.

Condition or Disease	Intervention/Treatment	Phase
Leg Spasticity	Biological: Botulinum toxin type A; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 388 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicentre, Double-blind, Prospective, Randomized, Placebo-controlled Study, Assessing the Efficacy and Safety of Dysport® Used for the Treatment of Lower-limb Spasticity in Adult Subjects With Hemiparesis Due to Stroke or Traumatic Brain Injury
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dysport® 1000 U, IM 1000 U, I.M. (in the muscle), on day 1 (single treatment cycle)	Biological: Botulinum toxin type A; I.M. injection on day 1 (single treatment cycle); Other Names: AbobotulinumtoxinA (Dysport®)
Experimental: Dysport® 1500 U, IM 1500 U, I.M., on day 1 (single treatment cycle)	Biological: Botulinum toxin type A; I.M. injection on day 1 (single treatment cycle); Other Names: AbobotulinumtoxinA (Dysport®)
Placebo Comparator: Placebo I.M., on day 1 (single treatment cycle)	Drug: Placebo; I.M. injection on day 1 (single treatment cycle)

Outcome Measures

Primary Outcome Measures

1. Least Squares Mean Change From Baseline to Week 4 in the MAS Score in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) [Baseline and 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.

Secondary Outcome Measures

1. Physician's Global Assesment (PGA) of Treatment Response at Week 4 [At Week 4]

   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.

2. Least Squares Mean Change From Baseline to Week 4 in Comfortable Barefoot Walking Speed [Baseline and Week 4]

   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.

Other Outcome Measures

1. Least Squares Mean Change From Baseline in MAS Score in the GSC (Knee Extended) at Weeks 1 and 12 [Baseline and Weeks 1 and 12]

   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.

2. Least Squares Mean Change From Baseline in MAS Score in the Soleus (Knee Flexed) at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

   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.

3. PGA of Treatment Response at Week 12 [At Week 12]

   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.

4. Least Squares Mean Change From Baseline in Comfortable Barefoot Walking Speed at Weeks 1 and 12 [Baseline and Weeks 1 and 12]

   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.

5. Least Squares Mean Change From Baseline in Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

   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.

6. Least Squares Mean Change From Baseline in Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

   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.

7. Least Squares Mean Change From Baseline in Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

   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.

8. Least Squares Mean Change From Baseline in Cadence With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

   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.

9. Least Squares Mean Change From Baseline in Average Step Length With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

   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.

10. Least Squares Mean Change From Baseline in Cadence With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

    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

11. Least Squares Mean Change From Baseline in Average Step Length With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

    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.

12. Least Squares Mean Change From Baseline in Cadence With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

    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.

13. Least Squares Mean Change From Baseline in Average Step Length With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

    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.

14. Least Squares Mean Change From Baseline in Cadence With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

    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.

15. Least Squares Mean Change From Baseline in Average Step Length With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

    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.

16. 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) [Baseline and Weeks 1, 4 and 12]

    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.

17. Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Spasticity Grade (Y) [Baseline and Weeks 1, 4 and 12]

    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.

18. 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) [Baseline and Weeks 1, 4 and 12]

    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.

19. Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Spasticity Grade (Y) [Baseline and Weeks 1, 4 and 12]

    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.

20. Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed) [Baseline and Weeks 1, 4 and 12]

    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.

21. Least Squares Mean Change From Baseline in Lower Limb Pain at Weeks 1, 4 and 12 [Baseline and Weeks 1, 4 and 12]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects aged 18 to 80 years of age

• Post stroke or brain injury

• Intensity of muscle tone greater than or equal to 2, as measured on the Modified Ashworth Scale

• Ambulatory patients

Exclusion Criteria:

• Fixed contractures

• Physiotherapy initiated less than 4 weeks before entry

• Previous surgery or previous treatment with phenol and/or alcohol in lower limb

• Neurological/neuromuscular disorders which may interfere with protocol evaluations

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Scottsdale	Arizona	United States	85259
2	Rancho Los Amigos	Downey	California	United States	90242
3	Pacific Neuroscience Medical Group	Oxnard	California	United States	93030
4	Associated Neurologists of Southern CT, PC	Fairfield	Connecticut	United States	06824
5	Parkinson's Disease & Movement Disorders Center of Boca Raton	Boca Raton	Florida	United States	33486
6	Design Neuroscience	Miami Gardens	Florida	United States	33169
7	Mount Sinai School of Medicine	New York	New York	United States	10029
8	Weill Cornell Medical College	New York	New York	United States	10065
9	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7200
10	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
11	MossRehab & Albert Einstein	Elkins Park	Pennsylvania	United States	19027
12	Vanderbilt University	Nashville	Tennessee	United States	37232
13	The University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390-9016
14	University of North Texas HSC at Ben Hogan Center	Fort Worth	Texas	United States	76104
15	Neurorehabilitation Specialist	Houston	Texas	United States	66211
16	University of Texas - Houston	Houston	Texas	United States	77030
17	University of Utah School of Medicine	Salt Lake City	Utah	United States	84132
18	Epworth HealthCare	Richmond	Victoria	Australia	3121
19	Caulfield Hospital	Caulfield		Australia	3162
20	Saint Vincent's Hospital	Darlinghurst		Australia
21	Saint Vincent's Hospital	Fitzroy		Australia
22	St George Hospital	Kogarah		Australia
23	Royal Melbourne Hospital	Parkville		Australia
24	Epworth Healthcare	Richmond		Australia
25	Westmead Hospital	Westmead		Australia
26	Université catholique de Louvain av Hippocrate 10	Bruxelles		Belgium
27	Clinique Universitaire	Yvoir		Belgium
28	Neurologicka Klinika	Olomouc		Czechia	775 20
29	Neurologicka Klinika, VFN	Praha		Czechia	12000
30	CHU Jean MINJOZ	Besançon		France
31	Service de Réeducation Fonctionnelle, CHU de Brest, Hôpital Morvan	Brest		France	29609
32	Centre de Réadaptation de Coubert	Coubert		France
33	Centre Hospitalier Albert Chenevier	Créteil		France
34	Hopital Raymond Poincarré	Garches		France
35	Hôpital de L'Archet	Nice		France
36	Hôpital Sébastopol, Médecine Physique et Réadaptation, CHU Reims	Reims		France	51092
37	Hôpital Sébastopol	Reims		France
38	Nouvel Civil Hospital	Strasbourg		France
39	Hopital Rangueil	Toulouse		France
40	National Institute for Medical Rehabilitation	Budapest		Hungary
41	Szent János Hospital	Budapest		Hungary
42	Uno Medical Trials	Budapest		Hungary
43	Petz Aladar Country Hospital	Gyor		Hungary
44	Batthyány Kázmér Hospital	Kisbér		Hungary
45	Azienda Ospedaliero	Catania		Italy
46	SSD Neurofisiologia Riabilitativa	Fossano		Italy
47	Servizio di Neurofisiologia Clinica-Ospedale San Raffaele	Milano		Italy
48	Polo IRCCS Eugenio Medea La Nostra Famiglia	Treviso		Italy
49	Specjalistyczna Praktyka Lekarska	Katowice		Poland
50	Centrum Medyczne Plejady	Krakow		Poland
51	Krakowska Akademia Neurologii	Krakow		Poland
52	Malopolskie Centrum Medyczne	Krakow		Poland
53	Nzoz Neuro - Card	Poznan		Poland
54	Samodzielny Publiczny Centralny Szpital	Warsaw		Poland
55	Servicio de Rehabilitation de Adultos	Alcabideche		Portugal
56	Centro Hospitalar Lisboa Norte	Lisbon		Portugal
57	Centro Hospitalar São João	Porto		Portugal
58	Treatments and Rehabilitation Center	Moscow		Russian Federation
59	State Institution "Scientific Centre of Neurology of Russian Academy of Medical Sciences"	Saint Petersburg		Russian Federation	125367
60	St-Petersberg State Medical University	St Petersburg		Russian Federation
61	Neurologicka klinika, Univerzitna nemocnica Bratislava	Bratislava		Slovakia	82606
62	Univerzitna Nemocnica Bratislava	Bratislava		Slovakia

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Study Director, Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT01249404
• Other Study ID Numbers: Y-55-52120-140; 2009-015868-34
• First Posted: Nov 29, 2010
• Last Update Posted: Aug 6, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Muscle Spasticity; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	A total of 456 subjects were screened, 388 were enrolled into the study and randomised to 1 of 3 treatment groups.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Period Title: Overall Study
STARTED	127	129	132
COMPLETED	120	121	125
NOT COMPLETED	7	8	7

Baseline Characteristics

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo	Total Title
Arm/Group Description	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).	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).	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 Participants	125	128	128	381
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.2 (13.2)	53.3 (12.0)	51.4 (12.9)	52.6 (12.7)
Sex: Female, Male (Count of Participants)
Female	38 30.4%	49 38.3%	38 29.7%	125 32.8%
Male	87 69.6%	79 61.7%	90 70.3%	256 67.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	3 2.4%	4 3.1%	3 2.3%	10 2.6%
Black or African American	5 4%	13 10.2%	5 3.9%	23 6%
Caucasian or White	116 92.8%	109 85.2%	119 93%	344 90.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.8%	0 0%	1 0.3%
Multiple	1 0.8%	1 0.8%	1 0.8%	3 0.8%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	14 11.2%	11 8.6%	11 8.6%	36 9.4%
Not Hispanic or Latino	111 88.8%	117 91.4%	117 91.4%	345 90.6%

Outcome Measures

1. Primary Outcome

Title	Least Squares Mean Change From Baseline to Week 4 in the MAS Score in the Gastrocnemius-soleus Complex (GSC) (Knee Extended)
Description	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.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Least Squares Mean (95% Confidence Interval) [units on a scale]	-0.6	-0.8	-0.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dysport® 1000 U, Placebo
	Comments	The least squares mean change from baseline to Week 4 for MAS in the Dysport® 1000 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect analysis of covariance (ANCOVA) model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.2859
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares (LS) mean difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, BTX treatment status at baseline and centre as covariates.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dysport® 1500 U, Placebo
	Comments	The least squares mean change from baseline to Week 4 for MAS in the Dysport® 1500 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect ANCOVA model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.0091
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.5 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, BTX treatment status at baseline and centre as covariates.

2. Secondary Outcome

Title	Physician's Global Assesment (PGA) of Treatment Response at Week 4
Description	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.
Time Frame	At Week 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	124	125	128
Least Squares Mean (95% Confidence Interval) [units on a scale]	0.9	0.9	0.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dysport® 1000 U, Placebo
	Comments	The mean PGA at Week 4 in the Dysport® 1000 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect ANCOVA model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.0640
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.0 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on visit results with treatment, BTX treatment status at baseline and centre as covariates.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dysport® 1500 U, Placebo
	Comments	The mean PGA at Week 4 in the Dysport® 1500 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect ANCOVA model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.0665
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.0 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on visit results with treatment, BTX treatment status at baseline and centre as covariates.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dysport® 1000 U, Placebo
	Comments	The LS mean rank values were back transformed to the original scale to give ranked PGA scores in an attempt to better normalise the data and restore power.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0466
	Comments
	Method	ANCOVA on rank PGA scores
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS means for each treatment group and treatment comparisons and the p-values are obtained from an analysis of variance on visit results based on ranked values with treatment, BTX treatment status at baseline and centre as explanatory variables.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Dysport® 1500 U, Placebo
	Comments	The LS mean rank values were back transformed to the original scale to give ranked PGA scores in an attempt to better normalise the data and restore power.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0406
	Comments
	Method	ANCOVA on rank PGA scores
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS means for each treatment group and treatment comparisons and the p-values are obtained from an analysis of variance on visit results based on ranked values with treatment, BTX treatment status at baseline and centre as explanatory variables.

3. Secondary Outcome

Title	Least Squares Mean Change From Baseline to Week 4 in Comfortable Barefoot Walking Speed
Description	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.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	124	127	126
Least Squares Mean (95% Confidence Interval) [m/s]	0.05	0.04	0.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dysport® 1000 U, Placebo
	Comments	The least squares mean change from baseline to Week 4 for barefoot comfortable walking speed in the Dysport® 1000 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect analysis of covariance (ANCOVA) model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.7247
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, BTX treatment status at baseline and centre as covariates.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dysport® 1500 U, Placebo
	Comments	The least squares mean change from baseline to Week 4 for barefoot comfortable walking speed in the Dysport® 1500 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect ANCOVA model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.7266
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, BTX treatment status at baseline and centre as covariates.

4. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in MAS Score in the GSC (Knee Extended) at Weeks 1 and 12
Description	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.
Time Frame	Baseline and Weeks 1 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	-0.4	-0.5	-0.4
Week 12	-0.4	-0.6	-0.4

5. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in MAS Score in the Soleus (Knee Flexed) at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	-0.4	-0.6	-0.4
Week 4	-0.7	-0.8	-0.4
Week 12	-0.5	-0.6	-0.3

6. Other Pre-specified Outcome

Title	PGA of Treatment Response at Week 12
Description	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.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	120	123	122
Least Squares Mean (95% Confidence Interval) [units on a scale]	0.6	0.6	0.5

7. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Comfortable Barefoot Walking Speed at Weeks 1 and 12
Description	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.
Time Frame	Baseline and Weeks 1 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.05	0.04	0.04
Week 12	0.07	0.06	0.05

8. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.05	0.05	0.04
Week 4	0.05	0.04	0.06
Week 12	0.06	0.05	0.05

9. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Maximal Barefoot Walking Speed at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.06	0.05	0.05
Week 4	0.07	0.04	0.05
Week 12	0.09	0.06	0.06

10. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Maximal Walking Speed With Shoes at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.05	0.05	0.04
Week 4	0.05	0.04	0.05
Week 12	0.07	0.05	0.05

11. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Cadence With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.07	0.07	0.04
Week 4	0.07	0.06	0.06
Week 12	0.09	0.06	0.05

12. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Average Step Length With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.02	0.02	0.02
Week 4	0.02	0.01	0.03
Week 12	0.02	0.02	0.03

13. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Cadence With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12
Description	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
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.10	0.05	0.05
Week 4	0.08	0.06	0.06
Week 12	0.12	0.08	0.07

14. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Average Step Length With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.02	0.02	0.01
Week 4	0.02	0.02	0.02
Week 12	0.02	0.02	0.02

15. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Cadence With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.06	0.07	0.04
Week 4	0.05	0.05	0.05
Week 12	0.08	0.07	0.04

16. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Average Step Length With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.02	0.01	0.02
Week 4	0.02	0.02	0.02
Week 12	0.02	0.02	0.03

17. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Cadence With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.07	0.05	0.06
Week 4	0.08	0.05	0.07
Week 12	0.12	0.08	0.06

18. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Average Step Length With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	0.02	0.02	0.02
Week 4	0.02	0.02	0.02
Week 12	0.02	0.02	0.02

19. Other Pre-specified Outcome

Title	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)
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1: Angle of Arrest (XV1)	2.4	2.3	1.7
Week 4: Angle of Arrest (XV1)	0.7	1.4	1.3
Week 12: Angle of Arrest (XV1)	0.4	0.4	0.5
Week 1: Angle of Catch (XV3)	5.1	5.4	3.2
Week 4: Angle of Catch (XV3)	4.8	5.3	3.4
Week 12: Angle of Catch (XV3)	3.0	2.9	2.6
Week 1: Spasticity Angle (X)	-2.5	-3.2	-1.7
Week 4: Spasticity Angle (X)	-4.0	-4.0	-2.5
Week 12: Spasticity Angle (X)	-2.4	-2.8	-2.3

20. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Spasticity Grade (Y)
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	-0.2	-0.3	-0.2
Week 4	-0.3	-0.4	-0.1
Week 12	-0.3	-0.4	-0.1

21. Other Pre-specified Outcome

Title	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)
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1: Angle of Arrest (XV1)	2.2	1.5	1.4
Week 4: Angle of Arrest (XV1)	1.2	1.0	1.3
Week 12: Angle of Arrest (XV1)	0.4	0.1	0.0
Week 1: Angle of Catch (XV3)	4.1	4.1	2.5
Week 4: Angle of Catch (XV3)	5.1	4.9	2.9
Week 12: Angle of Catch (XV3)	4.0	3.7	2.7
Week 1: Spasticity Angle (X)	-1.7	-2.8	-1.3
Week 4: Spasticity Angle (X)	-3.6	-4.2	-1.8
Week 12: Spasticity Angle (X)	-3.3	-3.9	-2.8

22. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Spasticity Grade (Y)
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	-0.2	-0.3	-0.1
Week 4	-0.5	-0.5	-0.1
Week 12	-0.4	-0.4	-0.1

23. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed)
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1: Knee Extended	1.7	2.4	1.1
Week 4: Knee Extended	1.5	3.7	1.6
Week 12: Knee Extended	1.1	2.0	1.7
Week 1: Knee Flexed	3.0	2.0	1.9
Week 4: Knee Flexed	2.9	3.3	2.7
Week 12: Knee Flexed	2.0	1.4	1.8

24. Other Pre-specified Outcome

Title	Least Squares Mean Change From Baseline in Lower Limb Pain at Weeks 1, 4 and 12
Description	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.
Time Frame	Baseline and Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dysport® 1000 U	Dysport® 1500 U	Placebo
Arm/Group Description	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).	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).	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.
Measure Participants	125	128	128
Week 1	-0.3	-0.1	-0.2
Week 4	-0.1	-0.2	-0.1
Week 12	-0.2	-0.1	0.1

Adverse Events

Time Frame	From baseline up to Week 24 +/- 2 weeks.
Adverse Event Reporting Description	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.
Arm/Group Title	Dysport® 1000 U		Dysport® 1500 U		Placebo
Arm/Group Description	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).		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).		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.
All Cause Mortality
	Dysport® 1000 U		Dysport® 1500 U		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dysport® 1000 U		Dysport® 1500 U		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/127 (3.9%)		5/128 (3.9%)		7/130 (5.4%)
Blood and lymphatic system disorders
Anaemia	0/127 (0%)	0	1/128 (0.8%)	1	0/130 (0%)	0
Cardiac disorders
Sinus tachycardia	1/127 (0.8%)	1	0/128 (0%)	0	0/130 (0%)	0
Congenital, familial and genetic disorders
Atrial septal defect	0/127 (0%)	0	0/128 (0%)	0	1/130 (0.8%)	1
General disorders
Chest pain	0/127 (0%)	0	0/128 (0%)	0	1/130 (0.8%)	1
Infections and infestations
Appendicitis	0/127 (0%)	0	1/128 (0.8%)	1	0/130 (0%)	0
Post procedural infection	0/127 (0%)	0	0/128 (0%)	0	1/130 (0.8%)	1
Pneumonia	0/127 (0%)	0	0/128 (0%)	0	1/130 (0.8%)	1
Injury, poisoning and procedural complications
Humerus fracture	1/127 (0.8%)	1	0/128 (0%)	0	0/130 (0%)	0
Femoral neck fracture	0/127 (0%)	0	0/128 (0%)	0	1/130 (0.8%)	1
Femur Fracture	0/127 (0%)	0	1/128 (0.8%)	1	0/130 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	0/127 (0%)	0	1/128 (0.8%)	1	0/130 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma	1/127 (0.8%)	1	0/128 (0%)	0	0/130 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/127 (0%)	0	1/128 (0.8%)	1	0/130 (0%)	0
Convulsion	2/127 (1.6%)	2	0/128 (0%)	0	1/130 (0.8%)	1
Ischaemic stroke	0/127 (0%)	0	0/128 (0%)	0	1/130 (0.8%)	1
Loss of consciousness	0/127 (0%)	0	0/128 (0%)	0	1/130 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/127 (0%)	0	1/128 (0.8%)	1	1/130 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Dysport® 1000 U		Dysport® 1500 U		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/127 (17.3%)		21/128 (16.4%)		11/130 (8.5%)
Injury, poisoning and procedural complications
Fall	12/127 (9.4%)	14	8/128 (6.3%)	9	4/130 (3.1%)	8
Musculoskeletal and connective tissue disorders
Pain in extremity	7/127 (5.5%)	7	8/128 (6.3%)	9	3/130 (2.3%)	3
Muscular weakness	3/127 (2.4%)	3	7/128 (5.5%)	8	4/130 (3.1%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.