Trial Outcomes & Findings for Dysport® Adult Lower Limb Spasticity Follow-on Study (NCT NCT01251367)

Last Updated: 2022-09-28

Results Overview

Adverse events (AEs) were monitored from the time that the subject gave informed consent to the end of the study/early withdrawal (EOS/EW). An AE was reported as a TEAE if it was not present prior to study treatment administration in Study 140, or if it was present prior to study treatment in Study 140 but the intensity increased during the treatment phase of this study. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any AE that was assessed as a hypersensitivity reaction. TEAEs, treatment related TEAEs, severe TEAEs, TEAEs leading to death, TEAEs leading to withdrawal, treatment emergent AESIs, and serious adverse events (SAEs) are summarised by treatment cycle.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

352 participants

Primary outcome timeframe

Up to EOS (maximum duration of 52 weeks).

Results posted on

2022-09-28

Participant Flow

The study was designed as a multicentre study and included 51 sites in Australia, Belgium, the Czech Republic, France, Hungary, Italy, Poland, Portugal, Russia, Slovakia and the United States of America that included at least one subject. The current study (Study 142) was an open label extension to the double blind Study 140 (Y-55-52120-140).

A total of 366 subjects completed Study 140, of which 352 subjects were enrolled in Study 142. Of these, 7 subjects entered an observational phase and never received open label treatment with Dysport® in Study 142 and the remaining 345 subjects started treatment and received at least one open label injection of Dysport® in Study 142.

Participant milestones

Participant milestones
Measure	Total Dysport® Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 Units \[U\] or 1000 U) by intramuscular (i.m.) injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Overall Study STARTED	345
Overall Study Cycle 1	345
Overall Study Cycle 2	297
Overall Study Cycle 3	224
Overall Study Cycle 4	139
Overall Study COMPLETED	269
Overall Study NOT COMPLETED	76

Reasons for withdrawal

Reasons for withdrawal
Measure	Total Dysport® Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 Units \[U\] or 1000 U) by intramuscular (i.m.) injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Overall Study Protocol Violation	1
Overall Study Lack of Efficacy	2
Overall Study Adverse Event	19
Overall Study Withdrawal by Subject	36
Overall Study Lost to Follow-up	5
Overall Study Subject Required Alternative Treatment	7
Overall Study No Study Drug Available	1
Overall Study Subject had Personal or Medical Issues	4
Overall Study End of Study Visit Performed in Error	1

Baseline Characteristics

Dysport® Adult Lower Limb Spasticity Follow-on Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	280 Participants n=93 Participants
Age, Categorical >=65 years	65 Participants n=93 Participants
Age, Continuous	53.1 years STANDARD_DEVIATION 12.8 • n=93 Participants
Sex: Female, Male Female	110 Participants n=93 Participants
Sex: Female, Male Male	235 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	34 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	311 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	7 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants
Race (NIH/OMB) Black or African American	21 Participants n=93 Participants
Race (NIH/OMB) White	313 Participants n=93 Participants
Race (NIH/OMB) More than one race	3 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: Up to EOS (maximum duration of 52 weeks).

Population: Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE - Cycle 1	140 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE - Cycle 2	97 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE - Cycle 3	47 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE - Cycle 4	21 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) Treatment Related TEAE - Cycle 1	43 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) Treatment Related TEAE - Cycle 2	23 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) Treatment Related TEAE - Cycle 3	7 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) Treatment Related TEAE - Cycle 4	5 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) Severe TEAE - Cycle 1	13 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) Severe TEAE - Cycle 2	9 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) Severe TEAE - Cycle 3	4 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) Severe TEAE - Cycle 4	2 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE leading to death - Cycle 1	0 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE leading to death - Cycle 2	1 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE leading to death - Cycle 3	1 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE leading to death - Cycle 4	0 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE leading to withdrawal - Cycle 1	8 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE leading to withdrawal - Cycle 2	10 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE leading to withdrawal - Cycle 3	1 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) TEAE leading to withdrawal - Cycle 4	0 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) AESI - Cycle 1	31 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) AESI - Cycle 2	24 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) AESI - Cycle 3	10 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) AESI - Cycle 4	5 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) SAE - Cycle 1	23 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) SAE - Cycle 2	14 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) SAE - Cycle 3	7 participants
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) SAE - Cycle 4	2 participants

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Systolic and diastolic BP were recorded at baseline and at each subsequent study visit. BP was measured with the subject in a sitting position after resting for 3 minutes. Mean change in BP from baseline at Week 4 is reported per cycle.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) Systolic BP - Cycle 1	-0.7 Millimetres Mercury (mmHg) Interval -67.0 to 37.0
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) Systolic BP - Cycle 2	-1.9 Millimetres Mercury (mmHg) Interval -69.0 to 37.0
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) Systolic BP - Cycle 3	-2.4 Millimetres Mercury (mmHg) Interval -58.0 to 79.0
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) Systolic BP - Cycle 4	-5.1 Millimetres Mercury (mmHg) Interval -73.0 to 25.0
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) Diastolic BP - Cycle 1	0.3 Millimetres Mercury (mmHg) Interval -34.0 to 37.0
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) Diastolic BP - Cycle 2	-0.2 Millimetres Mercury (mmHg) Interval -38.0 to 30.0
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) Diastolic BP - Cycle 3	-0.3 Millimetres Mercury (mmHg) Interval -32.0 to 28.0
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) Diastolic BP - Cycle 4	-1.1 Millimetres Mercury (mmHg) Interval -35.0 to 32.0

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

HR was recorded at baseline and at each subsequent study visit. HR was measured with the subject in a sitting position after resting for 3 minutes. Mean change in HR from baseline at Week 4 is reported per cycle.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Heart Rate (HR) Cycle 1	3.7 Beats per minute (bpm) Interval -28.0 to 39.0
Mean Change From Baseline to Week 4 in Heart Rate (HR) Cycle 2	4.9 Beats per minute (bpm) Interval -27.0 to 41.0
Mean Change From Baseline to Week 4 in Heart Rate (HR) Cycle 3	3.9 Beats per minute (bpm) Interval -25.0 to 52.0
Mean Change From Baseline to Week 4 in Heart Rate (HR) Cycle 4	4.5 Beats per minute (bpm) Interval -16.0 to 33.0

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples for RBC count were taken at baseline, at Week 4, and at EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count Cycle 1	0.049 Tera cells/Litre (L) Interval -0.51 to 0.66
Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count Cycle 2	0.074 Tera cells/Litre (L) Interval -0.59 to 0.68
Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count Cycle 3	0.046 Tera cells/Litre (L) Interval -0.59 to 0.66
Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count Cycle 4	0.028 Tera cells/Litre (L) Interval -1.24 to 0.61

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples for haemoglobin and MCHC were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) Haemoglobin - Cycle 1	1.2 grams (g)/L Interval -17.0 to 32.0
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) Haemoglobin - Cycle 2	1.5 grams (g)/L Interval -46.0 to 25.0
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) Haemoglobin - Cycle 3	1.5 grams (g)/L Interval -22.0 to 26.0
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) Haemoglobin - Cycle 4	1.2 grams (g)/L Interval -39.0 to 17.0
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) MCHC - Cycle 1	1.9 grams (g)/L Interval -29.0 to 34.0
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) MCHC - Cycle 2	1.3 grams (g)/L Interval -33.0 to 41.0
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) MCHC - Cycle 3	3.4 grams (g)/L Interval -23.0 to 33.0
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) MCHC - Cycle 4	8.9 grams (g)/L Interval -14.0 to 37.0

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples for haematocrit were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Haematocrit Cycle 1	0.001 percentage of RBC in blood Interval -0.057 to 0.081
Mean Change From Baseline to Week 4 in Haematocrit Cycle 2	0.003 percentage of RBC in blood Interval -0.107 to 0.098
Mean Change From Baseline to Week 4 in Haematocrit Cycle 3	-0.001 percentage of RBC in blood Interval -0.066 to 0.086
Mean Change From Baseline to Week 4 in Haematocrit Cycle 4	-0.009 percentage of RBC in blood Interval -0.12 to 0.047

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples for MCH were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH) Cycle 1	-0.06 picograms (pg) Interval -4.7 to 6.3
Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH) Cycle 2	-0.17 picograms (pg) Interval -9.3 to 4.6
Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH) Cycle 3	0.00 picograms (pg) Interval -2.8 to 5.3
Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH) Cycle 4	0.05 picograms (pg) Interval -1.8 to 2.0

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples for MCV were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV) Cycle 1	-0.74 Femtolitres (fL) Interval -10.3 to 14.8
Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV) Cycle 2	-0.9 Femtolitres (fL) Interval -21.2 to 12.5
Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV) Cycle 3	-1.02 Femtolitres (fL) Interval -8.5 to 13.7
Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV) Cycle 4	-2.44 Femtolitres (fL) Interval -9.1 to 3.7

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples for WBC count with differentials (neutrophils, lymphocytes) and platelet count were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets WBC count - Cycle 1	-0.21 Giga cells/L Interval -8.7 to 5.3
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets WBC count - Cycle 2	-0.32 Giga cells/L Interval -5.7 to 4.9
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets WBC count - Cycle 3	-0.26 Giga cells/L Interval -5.2 to 5.1
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets WBC count - Cycle 4	-0.02 Giga cells/L Interval -4.3 to 5.2
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Neutrophils - Cycle 1	-0.17 Giga cells/L Interval -7.5 to 4.5
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Neutrophils - Cycle 2	-0.27 Giga cells/L Interval -5.3 to 4.2
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Neutrophils - Cycle 3	-0.28 Giga cells/L Interval -5.6 to 4.8
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Neutrophils - Cycle 4	-0.06 Giga cells/L Interval -4.4 to 5.5
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Lymphocytes - Cycle 1	-0.05 Giga cells/L Interval -1.3 to 1.4
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Lymphocytes - Cycle 2	-0.05 Giga cells/L Interval -1.3 to 1.4
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Lymphocytes - Cycle 3	0.03 Giga cells/L Interval -1.2 to 2.5
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Lymphocytes - Cycle 4	-0.01 Giga cells/L Interval -0.9 to 2.0
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Platelets - Cycle 1	-0.1 Giga cells/L Interval -193.0 to 192.0
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Platelets - Cycle 2	0.0 Giga cells/L Interval -133.0 to 276.0
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Platelets - Cycle 3	0.1 Giga cells/L Interval -139.0 to 152.0
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets Platelets - Cycle 4	4.6 Giga cells/L Interval -67.0 to 167.0

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples were taken at baseline, at Week 4, and at the EOS/EW for analysis of the following clinical chemistry parameters: ALP, GGT, SGOT and SGPT. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) ALP - Cycle 1	-1.2 IU/L Interval -60.0 to 110.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) ALP - Cycle 2	-2.9 IU/L Interval -141.0 to 57.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) ALP - Cycle 3	-5.2 IU/L Interval -238.0 to 33.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) ALP - Cycle 4	-3.2 IU/L Interval -45.0 to 39.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) SGOT - Cycle 1	2.7 IU/L Interval -47.0 to 35.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) SGOT - Cycle 2	3 IU/L Interval -27.0 to 144.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) SGOT - Cycle 3	1.3 IU/L Interval -109.0 to 34.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) SGOT - Cycle 4	1.8 IU/L Interval -12.0 to 19.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) SGPT - Cycle 1	1.2 IU/L Interval -60.0 to 45.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) SGPT - Cycle 2	2.4 IU/L Interval -53.0 to 302.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) SGPT - Cycle 3	1.7 IU/L Interval -444.0 to 69.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) SGPT - Cycle 4	0.8 IU/L Interval -28.0 to 25.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) GGT - Cycle 1	1 IU/L Interval -122.0 to 614.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) GGT - Cycle 2	-1.9 IU/L Interval -145.0 to 121.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) GGT - Cycle 3	-3 IU/L Interval -254.0 to 107.0
Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) GGT - Cycle 4	-0.4 IU/L Interval -61.0 to 70.0

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples for clinical chemistry analysis of total bilirubin and creatinine were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine Total bilirubin - Cycle 1	0.13 Micromole/L (μmol/L) Interval -13.7 to 12.8
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine Total bilirubin - Cycle 2	0.14 Micromole/L (μmol/L) Interval -10.6 to 15.2
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine Total bilirubin - Cycle 3	0.03 Micromole/L (μmol/L) Interval -10.4 to 7.0
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine Total bilirubin - Cycle 4	-0.05 Micromole/L (μmol/L) Interval -9.1 to 16.1
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine Creatinine - Cycle 1	-2 Micromole/L (μmol/L) Interval -36.0 to 27.0
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine Creatinine - Cycle 2	-5.3 Micromole/L (μmol/L) Interval -36.0 to 35.0
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine Creatinine - Cycle 3	-7.9 Micromole/L (μmol/L) Interval -53.0 to 35.0
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine Creatinine - Cycle 4	-14.2 Micromole/L (μmol/L) Interval -62.0 to 9.0

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Blood samples for analysis of BUN and fasting blood glucose levels were taken at baseline, at Week 4 and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose BUN - Cycle 1	0.14 millimole/L (mmol/L) Interval -3.93 to 5.0
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose BUN - Cycle 2	-0.05 millimole/L (mmol/L) Interval -3.57 to 5.72
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose BUN - Cycle 3	-0.19 millimole/L (mmol/L) Interval -11.06 to 4.29
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose BUN - Cycle 4	-0.37 millimole/L (mmol/L) Interval -4.64 to 3.57
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose Fasting blood glucose - Cycle 1	-0.046 millimole/L (mmol/L) Interval -6.16 to 6.38
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose Fasting blood glucose - Cycle 2	0.009 millimole/L (mmol/L) Interval -4.17 to 9.44
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose Fasting blood glucose - Cycle 3	0.015 millimole/L (mmol/L) Interval -5.66 to 7.0
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose Fasting blood glucose - Cycle 4	0.231 millimole/L (mmol/L) Interval -3.44 to 8.61

PRIMARY outcome

Timeframe: At Week 4

Population: Subjects who received at least one open label injection of Dysport® were included in this analysis population. In addition, the antibody analysis included subjects who had an antibody assessment at baseline and at a post baseline visit (n=343).

Blood samples were collected at baseline, Week 4 and at EOS/EW to test for the presence of BTX-A antibodies. The number of subjects who were either NAb positive at baseline or negative at baseline but then positive following injection of Dysport® were reported.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport® Positive at baseline	3 Participants
Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport® Negative at baseline & positive post baseline	0 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4 of each cycle

Population: Subjects who received at least one open label injection of Dysport® were included in this analysis population.

12-lead ECG tracing was performed at baseline, at Week 4 of each cycle and at EOS/EW. The 12-lead ECG recordings were performed at a paper speed of 25 millimetres/second (mm/s), recorded with the subject in a supine position after 5 minutes rest. The ECG parameters; QT Duration, QT interval corrected with Fridericia's method (QTcF), QT interval corrected with Bazett's method (QTcB), QRS duration and PR duration were recorded and outcome measure is reported per cycle as change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=324 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QT Duration - Cycle 1	-10.1 Milliseconds (ms) Standard Deviation 24.9
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QT Duration - Cycle 2	-12.2 Milliseconds (ms) Standard Deviation 22.9
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QT Duration - Cycle 3	-13.6 Milliseconds (ms) Standard Deviation 26.5
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QT Duration - Cycle 4	-16.5 Milliseconds (ms) Standard Deviation 23.5
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QTcF - Cycle 1	-0.6 Milliseconds (ms) Standard Deviation 16.9
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QTcF - Cycle 2	-1.9 Milliseconds (ms) Standard Deviation 14.8
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QTcF - Cycle 3	-3.8 Milliseconds (ms) Standard Deviation 16.2
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QTcF - Cycle 4	-1.8 Milliseconds (ms) Standard Deviation 16.1
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QTcB - Cycle 1	4.5 Milliseconds (ms) Standard Deviation 20.2
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QTcB - Cycle 2	3.5 Milliseconds (ms) Standard Deviation 18.4
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QTcB - Cycle 3	1.5 Milliseconds (ms) Standard Deviation 19.5
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QTcB - Cycle 4	6.1 Milliseconds (ms) Standard Deviation 21.3
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QRS Duration - Cycle 1	-0.6 Milliseconds (ms) Standard Deviation 6.3
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QRS Duration - Cycle 2	-0.7 Milliseconds (ms) Standard Deviation 5.8
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QRS Duration - Cycle 3	-0.8 Milliseconds (ms) Standard Deviation 6.2
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) QRS Duration - Cycle 4	-0.9 Milliseconds (ms) Standard Deviation 6.7
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) PR Duration - Cycle 1	-2.2 Milliseconds (ms) Standard Deviation 14.5
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) PR Duration - Cycle 2	-1.7 Milliseconds (ms) Standard Deviation 15.2
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) PR Duration - Cycle 3	-0.5 Milliseconds (ms) Standard Deviation 14.4
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) PR Duration - Cycle 4	-0.6 Milliseconds (ms) Standard Deviation 13.4

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. 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. Outcome measure is reported per cycle as mean change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) Cycle 1	-0.8 units on a scale Standard Deviation 0.9
Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) Cycle 2	-0.9 units on a scale Standard Deviation 1
Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) Cycle 3	-1 units on a scale Standard Deviation 1
Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) Cycle 4	-1 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Muscle tone in the treated limb was assessed by MAS in the soleus muscle (with the knee flexed) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. 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. Outcome measure is reported per cycle as mean change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed) Cycle 1	-1 units on a scale Standard Deviation 1.2
Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed) Cycle 2	-1.1 units on a scale Standard Deviation 1
Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed) Cycle 3	-1.2 units on a scale Standard Deviation 1
Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed) Cycle 4	-1.1 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Week 4 of each cycle

Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. 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. Outcome measure is reported per cycle as the percentage of subjects with at least a 1 grade reduction or 2 grades reduction in MAS score at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 At least 1 grade reduction - Cycle 1	56.2 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 At least 1 grade reduction - Cycle 2	57.6 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 At least 1 grade reduction - Cycle 3	60.7 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 At least 1 grade reduction - Cycle 4	66.9 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 At least 2 grades reduction - Cycle 1	18.3 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 At least 2 grades reduction - Cycle 2	23.2 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 At least 2 grades reduction - Cycle 3	23.2 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 At least 2 grades reduction - Cycle 4	22.3 percentage of participants

SECONDARY outcome

Timeframe: Week 4 of each cycle

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 At least 1 grade reduction - Cycle 1	61.4 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 At least 1 grade reduction - Cycle 2	68.4 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 At least 1 grade reduction - Cycle 3	72.3 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 At least 1 grade reduction - Cycle 4	71.9 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 At least 2 grades reduction - Cycle 1	28.4 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 At least 2 grades reduction - Cycle 2	30.6 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 At least 2 grades reduction - Cycle 3	30.4 percentage of participants
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 At least 2 grades reduction - Cycle 4	28.8 percentage of participants

SECONDARY outcome

Timeframe: Week 4 of each cycle

An assessment of overall treatment response was conducted by the investigator at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. 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 nine-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 per cycle at Week 4 were reported.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Physician's Global Assessment (PGA) of Treatment Response at Week 4 Cycle 1	1.4 units on a scale Standard Deviation 1.1
Physician's Global Assessment (PGA) of Treatment Response at Week 4 Cycle 2	1.6 units on a scale Standard Deviation 1
Physician's Global Assessment (PGA) of Treatment Response at Week 4 Cycle 3	1.8 units on a scale Standard Deviation 1
Physician's Global Assessment (PGA) of Treatment Response at Week 4 Cycle 4	1.9 units on a scale Standard Deviation 1

SECONDARY outcome

Timeframe: Week 4 of each cycle

An assessment of overall treatment response was conducted by the investigator at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. 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 nine 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 percentage of responders with a PGA score of +1 or greater are reported at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4 Cycle 1	83.8 percentage of participants
Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4 Cycle 2	86.2 percentage of participants
Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4 Cycle 3	89.3 percentage of participants
Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4 Cycle 4	89.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Range of active dorsiflexion of the ankle joint of the treated limb, measured using a goniometre, both with the knee flexed (90°) and extended, was used to assess treatment response. The measurements were obtained at the end of baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended Knee Extended - Cycle 1	4.1 Degrees Standard Deviation 10.6
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended Knee Extended - Cycle 2	4.4 Degrees Standard Deviation 10.6
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended Knee Extended - Cycle 3	6 Degrees Standard Deviation 11.4
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended Knee Extended - Cycle 4	6.5 Degrees Standard Deviation 10.9
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended Knee Flexed - Cycle 1	4.1 Degrees Standard Deviation 10.7
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended Knee Flexed - Cycle 2	5 Degrees Standard Deviation 10.3
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended Knee Flexed - Cycle 3	5.2 Degrees Standard Deviation 10.9
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended Knee Flexed - Cycle 4	3.8 Degrees Standard Deviation 9.8

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

The intensity of lower limb pain in the treated limb was evaluated by the subject 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 at baseline, Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at the EOS/EW. The mean changes from baseline in subjects with a baseline SPIN Score \>0 at Week 4 was reported per cycle.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Lower Limb Pain Cycle 1	-0.7 units on a scale Standard Deviation 1.2
Mean Change From Baseline to Week 4 in Lower Limb Pain Cycle 2	-0.8 units on a scale Standard Deviation 1.2
Mean Change From Baseline to Week 4 in Lower Limb Pain Cycle 3	-0.9 units on a scale Standard Deviation 1.2
Mean Change From Baseline to Week 4 in Lower Limb Pain Cycle 4	-0.9 units on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Subjects were asked to complete the SF-36 health surveys prior to the study treatment at baseline, at Week 4 and at the EOS/EW visit. The SF-36 is a generic non preference based health status measure. This instrument assessed subject health across 8 variable dimensions, which are specific health domains such as physical functioning, social functioning and vitality. Each variable item score is coded and turned into a 0-100 scale where 0 indicates the worst and 100 indicates the best possible health state for both the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the questionnaire. The mean change in the PCS and MCS from baseline to Week 4 are reported.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) MCS - Cycle 4	0.14 units on a scale Standard Deviation 13.23
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) PCS - Cycle 1	1.05 units on a scale Standard Deviation 7.5
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) PCS - Cycle 2	1.43 units on a scale Standard Deviation 7.67
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) PCS - Cycle 3	1.85 units on a scale Standard Deviation 7.01
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) PCS - Cycle 4	2.8 units on a scale Standard Deviation 6.65
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) MCS - Cycle 1	-1.13 units on a scale Standard Deviation 11.27
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) MCS - Cycle 2	-0.82 units on a scale Standard Deviation 12.7
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) MCS - Cycle 3	0.56 units on a scale Standard Deviation 12.24

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Subjects were asked to complete the EQ-5D-5L QoL questionnaire prior to the study treatment at baseline, at Week 4 and at EOS/EW visit. The EQ-5D-5L index is a generic preference based measure of health related QoL producing utility scores that represent subject preferences for particular health states. This instrument rated subject health state looking at 5 specific dimensions such as mobility, self-care, usual activity, pain/discomfort and anxiety/ depression and scored their general health state. Each dimension has 5 levels of severity: no problems, slight problems, moderate problems, severe problems and extreme problems, rated from 1 to 5 (best to worst). In addition, a visual analogue scale (VAS) ranging from 0 to 100 was also included for the patients to summarize their overall health status, where 0 is the worst and 100 the best possible health state. The mean change in pain and discomfort and VAS scores from baseline to Week 4 are reported.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL Pain/discomfort - Cycle 1	-0.1 units on a scale Standard Deviation 1.0
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL Pain/discomfort - Cycle 2	-0.2 units on a scale Standard Deviation 1.0
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL Pain/discomfort - Cycle 3	-0.2 units on a scale Standard Deviation 1.0
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL Pain/discomfort - Cycle 4	-0.4 units on a scale Standard Deviation 1.2
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL VAS - Cycle 1	2.8 units on a scale Standard Deviation 18.3
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL VAS - Cycle 2	3.8 units on a scale Standard Deviation 17.7
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL VAS - Cycle 3	4.4 units on a scale Standard Deviation 19.9
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL VAS - Cycle 4	5.5 units on a scale Standard Deviation 21.0

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of WS were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Walking Speed (WS) Comfortable WS, barefoot - Cycle 1	0.07 metres/second (m/s) Standard Deviation 0.12
Mean Change From Baseline to Week 4 in Walking Speed (WS) Comfortable WS, barefoot - Cycle 2	0.08 metres/second (m/s) Standard Deviation 0.13
Mean Change From Baseline to Week 4 in Walking Speed (WS) Comfortable WS, barefoot - Cycle 3	0.08 metres/second (m/s) Standard Deviation 0.13
Mean Change From Baseline to Week 4 in Walking Speed (WS) Comfortable WS, barefoot - Cycle 4	0.09 metres/second (m/s) Standard Deviation 0.14
Mean Change From Baseline to Week 4 in Walking Speed (WS) Comfortable WS, with shoes - Cycle 1	0.06 metres/second (m/s) Standard Deviation 0.13
Mean Change From Baseline to Week 4 in Walking Speed (WS) Comfortable WS, with shoes - Cycle 2	0.07 metres/second (m/s) Standard Deviation 0.14
Mean Change From Baseline to Week 4 in Walking Speed (WS) Comfortable WS, with shoes - Cycle 3	0.08 metres/second (m/s) Standard Deviation 0.13
Mean Change From Baseline to Week 4 in Walking Speed (WS) Comfortable WS, with shoes - Cycle 4	0.08 metres/second (m/s) Standard Deviation 0.14
Mean Change From Baseline to Week 4 in Walking Speed (WS) Maximal WS, barefoot - Cycle 1	0.07 metres/second (m/s) Standard Deviation 0.16
Mean Change From Baseline to Week 4 in Walking Speed (WS) Maximal WS, barefoot - Cycle 2	0.08 metres/second (m/s) Standard Deviation 0.18
Mean Change From Baseline to Week 4 in Walking Speed (WS) Maximal WS, barefoot - Cycle 3	0.09 metres/second (m/s) Standard Deviation 0.18
Mean Change From Baseline to Week 4 in Walking Speed (WS) Maximal WS, barefoot - Cycle 4	0.1 metres/second (m/s) Standard Deviation 0.18
Mean Change From Baseline to Week 4 in Walking Speed (WS) Maximal WS, with shoes - Cycle 1	0.07 metres/second (m/s) Standard Deviation 0.17
Mean Change From Baseline to Week 4 in Walking Speed (WS) Maximal WS, with shoes - Cycle 2	0.09 metres/second (m/s) Standard Deviation 0.19
Mean Change From Baseline to Week 4 in Walking Speed (WS) Maximal WS, with shoes - Cycle 3	0.09 metres/second (m/s) Standard Deviation 0.19
Mean Change From Baseline to Week 4 in Walking Speed (WS) Maximal WS, with shoes - Cycle 4	0.1 metres/second (m/s) Standard Deviation 0.21

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of step length were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Step Length Comfortable WS, barefoot - Cycle 1	0.03 m/step Standard Deviation 0.06
Mean Change From Baseline to Week 4 in Step Length Comfortable WS, barefoot - Cycle 2	0.03 m/step Standard Deviation 0.09
Mean Change From Baseline to Week 4 in Step Length Comfortable WS, barefoot - Cycle 3	0.03 m/step Standard Deviation 0.08
Mean Change From Baseline to Week 4 in Step Length Comfortable WS, barefoot - Cycle 4	0.05 m/step Standard Deviation 0.09
Mean Change From Baseline to Week 4 in Step Length Comfortable WS, with shoes - Cycle 1	0.03 m/step Standard Deviation 0.07
Mean Change From Baseline to Week 4 in Step Length Comfortable WS, with shoes - Cycle 2	0.03 m/step Standard Deviation 0.08
Mean Change From Baseline to Week 4 in Step Length Comfortable WS, with shoes - Cycle 3	0.03 m/step Standard Deviation 0.08
Mean Change From Baseline to Week 4 in Step Length Comfortable WS, with shoes - Cycle 4	0.04 m/step Standard Deviation 0.09
Mean Change From Baseline to Week 4 in Step Length Maximal WS, barefoot - Cycle 1	0.03 m/step Standard Deviation 0.08
Mean Change From Baseline to Week 4 in Step Length Maximal WS, barefoot - Cycle 2	0.03 m/step Standard Deviation 0.09
Mean Change From Baseline to Week 4 in Step Length Maximal WS, barefoot - Cycle 3	0.03 m/step Standard Deviation 0.09
Mean Change From Baseline to Week 4 in Step Length Maximal WS, barefoot - Cycle 4	0.04 m/step Standard Deviation 0.09
Mean Change From Baseline to Week 4 in Step Length Maximal WS, with shoes - Cycle 1	0.02 m/step Standard Deviation 0.08
Mean Change From Baseline to Week 4 in Step Length Maximal WS, with shoes - Cycle 2	0.03 m/step Standard Deviation 0.09
Mean Change From Baseline to Week 4 in Step Length Maximal WS, with shoes - Cycle 3	0.03 m/step Standard Deviation 0.09
Mean Change From Baseline to Week 4 in Step Length Maximal WS, with shoes - Cycle 4	0.04 m/step Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of cadence were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Cadence Maximal WS, with shoes - Cycle 2	0.09 steps/s Standard Deviation 0.27
Mean Change From Baseline to Week 4 in Cadence Maximal WS, with shoes - Cycle 3	0.09 steps/s Standard Deviation 0.27
Mean Change From Baseline to Week 4 in Cadence Maximal WS, with shoes - Cycle 4	0.09 steps/s Standard Deviation 0.27
Mean Change From Baseline to Week 4 in Cadence Comfortable WS, barefoot - Cycle 1	0.08 steps/s Standard Deviation 0.21
Mean Change From Baseline to Week 4 in Cadence Comfortable WS, barefoot - Cycle 2	0.08 steps/s Standard Deviation 0.23
Mean Change From Baseline to Week 4 in Cadence Comfortable WS, barefoot - Cycle 3	0.08 steps/s Standard Deviation 0.21
Mean Change From Baseline to Week 4 in Cadence Comfortable WS, barefoot - Cycle 4	0.07 steps/s Standard Deviation 0.21
Mean Change From Baseline to Week 4 in Cadence Comfortable WS, with shoes - Cycle 1	0.07 steps/s Standard Deviation 0.21
Mean Change From Baseline to Week 4 in Cadence Comfortable WS, with shoes - Cycle 2	0.08 steps/s Standard Deviation 0.22
Mean Change From Baseline to Week 4 in Cadence Comfortable WS, with shoes - Cycle 3	0.08 steps/s Standard Deviation 0.22
Mean Change From Baseline to Week 4 in Cadence Comfortable WS, with shoes - Cycle 4	0.07 steps/s Standard Deviation 0.21
Mean Change From Baseline to Week 4 in Cadence Maximal WS, barefoot - Cycle 1	0.07 steps/s Standard Deviation 0.26
Mean Change From Baseline to Week 4 in Cadence Maximal WS, barefoot - Cycle 2	0.08 steps/s Standard Deviation 0.28
Mean Change From Baseline to Week 4 in Cadence Maximal WS, barefoot - Cycle 3	0.09 steps/s Standard Deviation 0.26
Mean Change From Baseline to Week 4 in Cadence Maximal WS, barefoot - Cycle 4	0.11 steps/s Standard Deviation 0.25
Mean Change From Baseline to Week 4 in Cadence Maximal WS, with shoes - Cycle 1	0.07 steps/s Standard Deviation 0.23

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Spasticity in the treated limb was assessed using the Tardieu Scale (TS) for the GSC (knee extended). The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported per cycle.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Angle of arrest (XV1) - Cycle 1	2.7 Degrees Standard Deviation 7.9
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Angle of arrest (XV1) - Cycle 2	2.4 Degrees Standard Deviation 7.8
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Angle of arrest (XV1) - Cycle 3	2.6 Degrees Standard Deviation 8.9
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Angle of arrest (XV1) - Cycle 4	2.7 Degrees Standard Deviation 8.4
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Angle of catch (XV3) - Cycle 1	7.1 Degrees Standard Deviation 10.6
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Angle of catch (XV3) - Cycle 2	7.3 Degrees Standard Deviation 11.1
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Angle of catch (XV3) - Cycle 3	7.9 Degrees Standard Deviation 12.2
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Angle of catch (XV3) - Cycle 4	9.5 Degrees Standard Deviation 12.4
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Spasticity angle (X) - Cycle 1	-4.4 Degrees Standard Deviation 8.6
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Spasticity angle (X) - Cycle 2	-4.9 Degrees Standard Deviation 9.2
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Spasticity angle (X) - Cycle 3	-5.4 Degrees Standard Deviation 9.3
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) Spasticity angle (X) - Cycle 4	-6.8 Degrees Standard Deviation 9.2

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Spasticity in the treated limb was assessed using the TS for the GSC (knee extended). The TS is administered by applying passive stretch to a muscle group. 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. Spasticity grade (Y) was recorded at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported per cycle.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended) Cycle 1	-0.5 units on a scale Standard Deviation 0.8
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended) Cycle 2	-0.5 units on a scale Standard Deviation 0.7
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended) Cycle 3	-0.5 units on a scale Standard Deviation 0.7
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended) Cycle 4	-0.5 units on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Spasticity in the treated limb was assessed using the TS for the soleus muscle (knee flexed). The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported per cycle.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Angle of arrest (XV1) - Cycle 1	1.9 Degrees Standard Deviation 8.0
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Angle of arrest (XV1) - Cycle 2	2.8 Degrees Standard Deviation 8.1
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Angle of arrest (XV1) - Cycle 3	2.6 Degrees Standard Deviation 8.5
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Angle of arrest (XV1) - Cycle 4	2.4 Degrees Standard Deviation 8.6
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Angle of catch (XV3) - Cycle 1	6.9 Degrees Standard Deviation 10.3
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Angle of catch (XV3) - Cycle 2	7.5 Degrees Standard Deviation 10.8
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Angle of catch (XV3) - Cycle 3	7.8 Degrees Standard Deviation 11.2
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Angle of catch (XV3) - Cycle 4	8.8 Degrees Standard Deviation 11.4
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Spasticity angle (X) - Cycle 1	-5.0 Degrees Standard Deviation 10.0
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Spasticity angle (X) - Cycle 2	-4.7 Degrees Standard Deviation 9.8
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Spasticity angle (X) - Cycle 3	-5.2 Degrees Standard Deviation 9.6
Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) Spasticity angle (X) - Cycle 4	-6.4 Degrees Standard Deviation 11.1

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Spasticity in the treated limb was assessed using the TS for the soleus muscle (knee flexed). The TS is administered by applying passive stretch to a muscle group. 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. Spasticity grade (Y) was recorded at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported per cycle.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed) Cycle 1	-0.6 units on a scale Standard Deviation 0.8
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed) Cycle 2	-0.6 units on a scale Standard Deviation 0.7
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed) Cycle 3	-0.7 units on a scale Standard Deviation 0.8
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed) Cycle 4	-0.7 units on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline and Week 4 of each cycle

Subjects were assessed on their use of walking aids and orthoses at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at the EOS/EW visit. Outcome measure is reported per cycle at baseline and Week 4. Number of subjects with no walking aid/orthoses were included in the 'No Walking Aid' category and number of subjects with any kind of walking aid/orthosis (including single point cane, tripod cane, ankle foot orthosis or other type of walking aid/orthosis) were combined into the 'Walking Aid' category.

Outcome measures

Outcome measures
Measure	Total Dysport® n=345 Participants Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Use of Walking Aids/Orthoses at Baseline and Week 4 No Walking Aid at Week 4 - Cycle 2	80 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 Walking Aid at Week 4 - Cycle 2	212 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 No Walking Aid at Baseline - Cycle 3	56 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 Walking Aid at Baseline - Cycle 3	168 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 No Walking Aid at Week 4 - Cycle 3	59 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 Walking Aid at Week 4 - Cycle 3	147 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 No Walking Aid at Baseline - Cycle 4	40 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 Walking Aid at Baseline - Cycle 4	99 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 No Walking Aid at Week 4 - Cycle 4	33 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 Walking Aid at Week 4 - Cycle 4	64 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 No Walking Aid at Baseline - Cycle 1	101 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 Walking Aid at Baseline - Cycle 1	244 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 No Walking Aid at Week 4 - Cycle 1	99 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 Walking Aid at Week 4 - Cycle 1	242 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 No Walking Aid at Baseline - Cycle 2	84 Participants
Use of Walking Aids/Orthoses at Baseline and Week 4 Walking Aid at Baseline - Cycle 2	213 Participants

Adverse Events

Total Dysport®

Serious events: 43 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Total Dysport® n=345 participants at risk Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Vascular disorders Venous thrombosis	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Vascular disorders Haematoma	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Injury, poisoning and procedural complications Subdural haemorrhage	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Injury, poisoning and procedural complications Wrist fracture	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Injury, poisoning and procedural complications Concussion	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Injury, poisoning and procedural complications Head injury	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Injury, poisoning and procedural complications Fibula fracture	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Cardiac disorders Atrial fibrillation	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Cardiac disorders Coronary artery dissection	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Cardiac disorders Acute myocardial infarction	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Cardiac disorders Coronary artery disease	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Cardiac disorders Myocardial infarction	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.29% 1/345 • Number of events 2 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Nervous system disorders Cerebral haemorrhage	0.58% 2/345 • Number of events 2 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Nervous system disorders Presyncope	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Nervous system disorders Epilepsy	1.4% 5/345 • Number of events 5 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Nervous system disorders Syncope	0.58% 2/345 • Number of events 2 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Nervous system disorders Transient ischaemic attack	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Nervous system disorders Seizure	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Nervous system disorders Cerebrovascular accident	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
General disorders Asthenia	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
General disorders Gait disturbance	0.58% 2/345 • Number of events 2 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
General disorders Chest pain	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Psychiatric disorders Completed suicide	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Psychiatric disorders Anxiety	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Psychiatric disorders Suicidal ideation	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Psychiatric disorders Suicide attempt	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Gastrointestinal disorders Dysphagia	0.58% 2/345 • Number of events 2 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Gastrointestinal disorders Dyspepsia	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Gastrointestinal disorders Diarrhoea	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Gastrointestinal disorders Intestinal polyp	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Hepatobiliary disorders Cholecystitis	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Hepatobiliary disorders Cholecystitis acute	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Musculoskeletal and connective tissue disorders Muscular weakness	0.87% 3/345 • Number of events 3 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Infections and infestations Pneumonia	0.87% 3/345 • Number of events 3 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Infections and infestations Bronchitis	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Infections and infestations Anal abscess	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Infections and infestations Appendicitis	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Infections and infestations Urinary tract infection	0.29% 1/345 • Number of events 1 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.

Other adverse events

Other adverse events
Measure	Total Dysport® n=345 participants at risk Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Injury, poisoning and procedural complications Fall	12.2% 42/345 • Number of events 52 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.
Musculoskeletal and connective tissue disorders Muscular weakness	10.4% 36/345 • Number of events 41 • From baseline to EOS (maximum duration of 52 weeks). AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study.

Additional Information

Medical Director, Neurology,

Ipsen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place