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Dysport® Adult Lower Limb Spasticity Follow-on Study

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ClinicalTrials.gov Identifier: NCT01251367
Recruitment Status : Completed
First Posted : December 1, 2010
Results First Posted : November 9, 2017
Last Update Posted : November 9, 2017
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Post-stroke Spasticity
Spasticity Post-Traumatic Brain Injury
Intervention: Drug: Dysport®

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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).

Participant Flow:   Overall Study
    Total Dysport®
STARTED   345 
Cycle 1   345 
Cycle 2   297 
Cycle 3   224 
Cycle 4   139 
COMPLETED   269 
NOT COMPLETED   76 
Protocol Violation                1 
Lack of Efficacy                2 
Adverse Event                19 
Withdrawal by Subject                36 
Lost to Follow-up                5 
Subject Required Alternative Treatment                7 
No Study Drug Available                1 
Subject had Personal or Medical Issues                4 
End of Study Visit Performed in Error                1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The summary of baseline characteristics presented are from subjects completing Study 140 who were selected by the investigator for entry into Study 142 and received at least one injection of study treatment in this open label extension study.

Reporting Groups
  Description
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 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).

Baseline Measures
   Total Dysport® 
Overall Participants Analyzed 
[Units: Participants]
 345 
Age 
[Units: Participants]
Count of Participants
 
<=18 years      0   0.0% 
Between 18 and 65 years      280  81.2% 
>=65 years      65  18.8% 
Age 
[Units: Years]
Mean (Standard Deviation)
 53.1  (12.8) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      110  31.9% 
Male      235  68.1% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
 
Hispanic or Latino      34   9.9% 
Not Hispanic or Latino      311  90.1% 
Unknown or Not Reported      0   0.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
 
American Indian or Alaska Native      0   0.0% 
Asian      7   2.0% 
Native Hawaiian or Other Pacific Islander      1   0.3% 
Black or African American      21   6.1% 
White      313  90.7% 
More than one race      3   0.9% 
Unknown or Not Reported      0   0.0% 


  Outcome Measures

1.  Primary:   Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)   [ Time Frame: Up to EOS (maximum duration of 52 weeks). ]

Measure Type Primary
Measure Title Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Measure Description 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.
Time Frame Up to EOS (maximum duration of 52 weeks).  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) 
[Units: Participants]
 
TEAE - Cycle 1   
Participants Analyzed   345 
TEAE - Cycle 1   140 
TEAE - Cycle 2   
Participants Analyzed   297 
TEAE - Cycle 2   97 
TEAE - Cycle 3   
Participants Analyzed   224 
TEAE - Cycle 3   47 
TEAE - Cycle 4   
Participants Analyzed   139 
TEAE - Cycle 4   21 
Treatment Related TEAE - Cycle 1   
Participants Analyzed   345 
Treatment Related TEAE - Cycle 1   43 
Treatment Related TEAE - Cycle 2   
Participants Analyzed   297 
Treatment Related TEAE - Cycle 2   23 
Treatment Related TEAE - Cycle 3   
Participants Analyzed   224 
Treatment Related TEAE - Cycle 3   7 
Treatment Related TEAE - Cycle 4   
Participants Analyzed   139 
Treatment Related TEAE - Cycle 4   5 
Severe TEAE - Cycle 1   
Participants Analyzed   345 
Severe TEAE - Cycle 1   13 
Severe TEAE - Cycle 2   
Participants Analyzed   297 
Severe TEAE - Cycle 2   9 
Severe TEAE - Cycle 3   
Participants Analyzed   224 
Severe TEAE - Cycle 3   4 
Severe TEAE - Cycle 4   
Participants Analyzed   139 
Severe TEAE - Cycle 4   2 
TEAE leading to death - Cycle 1   
Participants Analyzed   345 
TEAE leading to death - Cycle 1   0 
TEAE leading to death - Cycle 2   
Participants Analyzed   297 
TEAE leading to death - Cycle 2   1 
TEAE leading to death - Cycle 3   
Participants Analyzed   224 
TEAE leading to death - Cycle 3   1 
TEAE leading to death - Cycle 4   
Participants Analyzed   139 
TEAE leading to death - Cycle 4   0 
TEAE leading to withdrawal - Cycle 1   
Participants Analyzed   345 
TEAE leading to withdrawal - Cycle 1   8 
TEAE leading to withdrawal - Cycle 2   
Participants Analyzed   297 
TEAE leading to withdrawal - Cycle 2   10 
TEAE leading to withdrawal - Cycle 3   
Participants Analyzed   224 
TEAE leading to withdrawal - Cycle 3   1 
TEAE leading to withdrawal - Cycle 4   
Participants Analyzed   139 
TEAE leading to withdrawal - Cycle 4   0 
AESI - Cycle 1   
Participants Analyzed   345 
AESI - Cycle 1   31 
AESI - Cycle 2   
Participants Analyzed   297 
AESI - Cycle 2   24 
AESI - Cycle 3   
Participants Analyzed   224 
AESI - Cycle 3   10 
AESI - Cycle 4   
Participants Analyzed   139 
AESI - Cycle 4   5 
SAE - Cycle 1   
Participants Analyzed   345 
SAE - Cycle 1   23 
SAE - Cycle 2   
Participants Analyzed   297 
SAE - Cycle 2   14 
SAE - Cycle 3   
Participants Analyzed   224 
SAE - Cycle 3   7 
SAE - Cycle 4   
Participants Analyzed   139 
SAE - Cycle 4   2 

No statistical analysis provided for Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)



2.  Primary:   Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) 
[Units: Millimetres Mercury (mmHg)]
Mean (Full Range)
 
Systolic BP - Cycle 1   
Participants Analyzed   331 
Systolic BP - Cycle 1   -0.7 
 (-67 to 37) 
Systolic BP - Cycle 2   
Participants Analyzed   281 
Systolic BP - Cycle 2   -1.9 
 (-69 to 37) 
Systolic BP - Cycle 3   
Participants Analyzed   200 
Systolic BP - Cycle 3   -2.4 
 (-58 to 79) 
Systolic BP - Cycle 4   
Participants Analyzed   92 
Systolic BP - Cycle 4   -5.1 
 (-73 to 25) 
Diastolic BP - Cycle 1   
Participants Analyzed   331 
Diastolic BP - Cycle 1   0.3 
 (-34 to 37) 
Diastolic BP - Cycle 2   
Participants Analyzed   281 
Diastolic BP - Cycle 2   -0.2 
 (-38 to 30) 
Diastolic BP - Cycle 3   
Participants Analyzed   200 
Diastolic BP - Cycle 3   -0.3 
 (-32 to 28) 
Diastolic BP - Cycle 4   
Participants Analyzed   92 
Diastolic BP - Cycle 4   -1.1 
 (-35 to 32) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP)



3.  Primary:   Mean Change From Baseline to Week 4 in Heart Rate (HR)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Heart Rate (HR)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Heart Rate (HR) 
[Units: Beats per minute (bpm)]
Mean (Full Range)
 
Cycle 1   
Participants Analyzed   331 
Cycle 1   3.7 
 (-28 to 39) 
Cycle 2   
Participants Analyzed   281 
Cycle 2   4.9 
 (-27 to 41) 
Cycle 3   
Participants Analyzed   200 
Cycle 3   3.9 
 (-25 to 52) 
Cycle 4   
Participants Analyzed   92 
Cycle 4   4.5 
 (-16 to 33) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Heart Rate (HR)



4.  Primary:   Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count 
[Units: Tera cells/Litre (L)]
Mean (Full Range)
 
Cycle 1   
Participants Analyzed   305 
Cycle 1   0.049 
 (-0.51 to 0.66) 
Cycle 2   
Participants Analyzed   260 
Cycle 2   0.074 
 (-0.59 to 0.68) 
Cycle 3   
Participants Analyzed   180 
Cycle 3   0.046 
 (-0.59 to 0.66) 
Cycle 4   
Participants Analyzed   78 
Cycle 4   0.028 
 (-1.24 to 0.61) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count



5.  Primary:   Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) 
[Units: Grams (g)/L]
Mean (Full Range)
 
Haemoglobin - Cycle 1   
Participants Analyzed   305 
Haemoglobin - Cycle 1   1.2 
 (-17 to 32) 
Haemoglobin - Cycle 2   
Participants Analyzed   260 
Haemoglobin - Cycle 2   1.5 
 (-46 to 25) 
Haemoglobin - Cycle 3   
Participants Analyzed   180 
Haemoglobin - Cycle 3   1.5 
 (-22 to 26) 
Haemoglobin - Cycle 4   
Participants Analyzed   78 
Haemoglobin - Cycle 4   1.2 
 (-39 to 17) 
MCHC - Cycle 1   
Participants Analyzed   305 
MCHC - Cycle 1   1.9 
 (-29 to 34) 
MCHC - Cycle 2   
Participants Analyzed   260 
MCHC - Cycle 2   1.3 
 (-33 to 41) 
MCHC - Cycle 3   
Participants Analyzed   180 
MCHC - Cycle 3   3.4 
 (-23 to 33) 
MCHC - Cycle 4   
Participants Analyzed   78 
MCHC - Cycle 4   8.9 
 (-14 to 37) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)



6.  Primary:   Mean Change From Baseline to Week 4 in Haematocrit   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Haematocrit
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Haematocrit 
[Units: Percentage of RBC in blood]
Mean (Full Range)
 
Cycle 1   
Participants Analyzed   305 
Cycle 1   0.001 
 (-0.057 to 0.081) 
Cycle 2   
Participants Analyzed   260 
Cycle 2   0.003 
 (-0.107 to 0.098) 
Cycle 3   
Participants Analyzed   180 
Cycle 3   -0.001 
 (-0.066 to 0.086) 
Cycle 4   
Participants Analyzed   78 
Cycle 4   -0.009 
 (-0.12 to 0.047) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Haematocrit



7.  Primary:   Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH) 
[Units: Picograms (pg)]
Mean (Full Range)
 
Cycle 1   
Participants Analyzed   305 
Cycle 1   -0.06 
 (-4.7 to 6.3) 
Cycle 2   
Participants Analyzed   260 
Cycle 2   -0.17 
 (-9.3 to 4.6) 
Cycle 3   
Participants Analyzed   180 
Cycle 3   0.00 
 (-2.8 to 5.3) 
Cycle 4   
Participants Analyzed   78 
Cycle 4   0.05 
 (-1.8 to 2) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH)



8.  Primary:   Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV) 
[Units: Femtolitres (fL)]
Mean (Full Range)
 
Cycle 1   
Participants Analyzed   305 
Cycle 1   -0.74 
 (-10.3 to 14.8) 
Cycle 2   
Participants Analyzed   260 
Cycle 2   -0.9 
 (-21.2 to 12.5) 
Cycle 3   
Participants Analyzed   180 
Cycle 3   -1.02 
 (-8.5 to 13.7) 
Cycle 4   
Participants Analyzed   78 
Cycle 4   -2.44 
 (-9.1 to 3.7) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV)



9.  Primary:   Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets 
[Units: Giga cells/L]
Mean (Full Range)
 
WBC count - Cycle 1   
Participants Analyzed   305 
WBC count - Cycle 1   -0.21 
 (-8.7 to 5.3) 
WBC count - Cycle 2   
Participants Analyzed   260 
WBC count - Cycle 2   -0.32 
 (-5.7 to 4.9) 
WBC count - Cycle 3   
Participants Analyzed   180 
WBC count - Cycle 3   -0.26 
 (-5.2 to 5.1) 
WBC count - Cycle 4   
Participants Analyzed   78 
WBC count - Cycle 4   -0.02 
 (-4.3 to 5.2) 
Neutrophils - Cycle 1   
Participants Analyzed   304 
Neutrophils - Cycle 1   -0.17 
 (-7.5 to 4.5) 
Neutrophils - Cycle 2   
Participants Analyzed   259 
Neutrophils - Cycle 2   -0.27 
 (-5.3 to 4.2) 
Neutrophils - Cycle 3   
Participants Analyzed   179 
Neutrophils - Cycle 3   -0.28 
 (-5.6 to 4.8) 
Neutrophils - Cycle 4   
Participants Analyzed   78 
Neutrophils - Cycle 4   -0.06 
 (-4.4 to 5.5) 
Lymphocytes - Cycle 1   
Participants Analyzed   303 
Lymphocytes - Cycle 1   -0.05 
 (-1.3 to 1.4) 
Lymphocytes - Cycle 2   
Participants Analyzed   258 
Lymphocytes - Cycle 2   -0.05 
 (-1.3 to 1.4) 
Lymphocytes - Cycle 3   
Participants Analyzed   179 
Lymphocytes - Cycle 3   0.03 
 (-1.2 to 2.5) 
Lymphocytes - Cycle 4   
Participants Analyzed   78 
Lymphocytes - Cycle 4   -0.01 
 (-0.9 to 2) 
Platelets - Cycle 1   
Participants Analyzed   300 
Platelets - Cycle 1   -0.1 
 (-193 to 192) 
Platelets - Cycle 2   
Participants Analyzed   257 
Platelets - Cycle 2   0.0 
 (-133 to 276) 
Platelets - Cycle 3   
Participants Analyzed   178 
Platelets - Cycle 3   0.1 
 (-139 to 152) 
Platelets - Cycle 4   
Participants Analyzed   77 
Platelets - Cycle 4   4.6 
 (-67 to 167) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets



10.  Primary:   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)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title 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)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
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) 
[Units: IU/L]
Mean (Full Range)
 
ALP - Cycle 1   
Participants Analyzed   319 
ALP - Cycle 1   -1.2 
 (-60 to 110) 
ALP - Cycle 2   
Participants Analyzed   268 
ALP - Cycle 2   -2.9 
 (-141 to 57) 
ALP - Cycle 3   
Participants Analyzed   188 
ALP - Cycle 3   -5.2 
 (-238 to 33) 
ALP - Cycle 4   
Participants Analyzed   85 
ALP - Cycle 4   -3.2 
 (-45 to 39) 
SGOT - Cycle 1   
Participants Analyzed   319 
SGOT - Cycle 1   2.7 
 (-47 to 35) 
SGOT - Cycle 2   
Participants Analyzed   268 
SGOT - Cycle 2   3 
 (-27 to 144) 
SGOT - Cycle 3   
Participants Analyzed   188 
SGOT - Cycle 3   1.3 
 (-109 to 34) 
SGOT - Cycle 4   
Participants Analyzed   85 
SGOT - Cycle 4   1.8 
 (-12 to 19) 
SGPT - Cycle 1   
Participants Analyzed   319 
SGPT - Cycle 1   1.2 
 (-60 to 45) 
SGPT - Cycle 2   
Participants Analyzed   268 
SGPT - Cycle 2   2.4 
 (-53 to 302) 
SGPT - Cycle 3   
Participants Analyzed   188 
SGPT - Cycle 3   1.7 
 (-444 to 69) 
SGPT - Cycle 4   
Participants Analyzed   85 
SGPT - Cycle 4   0.8 
 (-28 to 25) 
GGT - Cycle 1   
Participants Analyzed   320 
GGT - Cycle 1   1 
 (-122 to 614) 
GGT - Cycle 2   
Participants Analyzed   268 
GGT - Cycle 2   -1.9 
 (-145 to 121) 
GGT - Cycle 3   
Participants Analyzed   188 
GGT - Cycle 3   -3 
 (-254 to 107) 
GGT - Cycle 4   
Participants Analyzed   85 
GGT - Cycle 4   -0.4 
 (-61 to 70) 

No statistical analysis provided for 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)



11.  Primary:   Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine 
[Units: Micromole/L (μmol/L)]
Mean (Full Range)
 
Total bilirubin - Cycle 1   
Participants Analyzed   319 
Total bilirubin - Cycle 1   0.13 
 (-13.7 to 12.8) 
Total bilirubin - Cycle 2   
Participants Analyzed   268 
Total bilirubin - Cycle 2   0.14 
 (-10.6 to 15.2) 
Total bilirubin - Cycle 3   
Participants Analyzed   188 
Total bilirubin - Cycle 3   0.03 
 (-10.4 to 7) 
Total bilirubin - Cycle 4   
Participants Analyzed   85 
Total bilirubin - Cycle 4   -0.05 
 (-9.1 to 16.1) 
Creatinine - Cycle 1   
Participants Analyzed   320 
Creatinine - Cycle 1   -2 
 (-36 to 27) 
Creatinine - Cycle 2   
Participants Analyzed   268 
Creatinine - Cycle 2   -5.3 
 (-36 to 35) 
Creatinine - Cycle 3   
Participants Analyzed   188 
Creatinine - Cycle 3   -7.9 
 (-53 to 35) 
Creatinine - Cycle 4   
Participants Analyzed   85 
Creatinine - Cycle 4   -14.2 
 (-62 to 9) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine



12.  Primary:   Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose 
[Units: millimole/L (mmol/L)]
Mean (Full Range)
 
BUN - Cycle 1   
Participants Analyzed   320 
BUN - Cycle 1   0.14 
 (-3.93 to 5) 
BUN - Cycle 2   
Participants Analyzed   268 
BUN - Cycle 2   -0.05 
 (-3.57 to 5.72) 
BUN - Cycle 3   
Participants Analyzed   188 
BUN - Cycle 3   -0.19 
 (-11.06 to 4.29) 
BUN - Cycle 4   
Participants Analyzed   85 
BUN - Cycle 4   -0.37 
 (-4.64 to 3.57) 
Fasting blood glucose - Cycle 1   
Participants Analyzed   169 
Fasting blood glucose - Cycle 1   -0.046 
 (-6.16 to 6.38) 
Fasting blood glucose - Cycle 2   
Participants Analyzed   143 
Fasting blood glucose - Cycle 2   0.009 
 (-4.17 to 9.44) 
Fasting blood glucose - Cycle 3   
Participants Analyzed   101 
Fasting blood glucose - Cycle 3   0.015 
 (-5.66 to 7) 
Fasting blood glucose - Cycle 4   
Participants Analyzed   55 
Fasting blood glucose - Cycle 4   0.231 
 (-3.44 to 8.61) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose



13.  Primary:   Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport®   [ Time Frame: At Week 4 ]

Measure Type Primary
Measure Title Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport®
Measure Description 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.
Time Frame At Week 4  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport® 
[Units: Participants]
Count of Participants
 
Positive at baseline   
Participants Analyzed   343 
Positive at baseline   3 
Negative at baseline & positive post baseline   
Participants Analyzed   343 
Negative at baseline & positive post baseline   0 

No statistical analysis provided for Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport®



14.  Primary:   Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Primary
Measure Title Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects who received at least one open label injection of Dysport® were included in this analysis population.

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   324 
Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) 
[Units: Milliseconds (ms)]
Mean (Standard Deviation)
 
QT Duration – Cycle 1   
Participants Analyzed   301 
QT Duration – Cycle 1   -10.1  (24.9) 
QT Duration – Cycle 2   
Participants Analyzed   260 
QT Duration – Cycle 2   -12.2  (22.9) 
QT Duration – Cycle 3   
Participants Analyzed   181 
QT Duration – Cycle 3   -13.6  (26.5) 
QT Duration – Cycle 4   
Participants Analyzed   83 
QT Duration – Cycle 4   -16.5  (23.5) 
QTcF – Cycle 1   
Participants Analyzed   301 
QTcF – Cycle 1   -0.6  (16.9) 
QTcF – Cycle 2   
Participants Analyzed   260 
QTcF – Cycle 2   -1.9  (14.8) 
QTcF – Cycle 3   
Participants Analyzed   181 
QTcF – Cycle 3   -3.8  (16.2) 
QTcF – Cycle 4   
Participants Analyzed   83 
QTcF – Cycle 4   -1.8  (16.1) 
QTcB – Cycle 1   
Participants Analyzed   301 
QTcB – Cycle 1   4.5  (20.2) 
QTcB – Cycle 2   
Participants Analyzed   260 
QTcB – Cycle 2   3.5  (18.4) 
QTcB – Cycle 3   
Participants Analyzed   181 
QTcB – Cycle 3   1.5  (19.5) 
QTcB – Cycle 4   
Participants Analyzed   83 
QTcB – Cycle 4   6.1  (21.3) 
QRS Duration – Cycle 1   
Participants Analyzed   301 
QRS Duration – Cycle 1   -0.6  (6.3) 
QRS Duration – Cycle 2   
Participants Analyzed   260 
QRS Duration – Cycle 2   -0.7  (5.8) 
QRS Duration – Cycle 3   
Participants Analyzed   181 
QRS Duration – Cycle 3   -0.8  (6.2) 
QRS Duration – Cycle 4   
Participants Analyzed   83 
QRS Duration – Cycle 4   -0.9  (6.7) 
PR Duration – Cycle 1   
Participants Analyzed   300 
PR Duration – Cycle 1   -2.2  (14.5) 
PR Duration – Cycle 2   
Participants Analyzed   259 
PR Duration – Cycle 2   -1.7  (15.2) 
PR Duration – Cycle 3   
Participants Analyzed   181 
PR Duration – Cycle 3   -0.5  (14.4) 
PR Duration – Cycle 4   
Participants Analyzed   83 
PR Duration – Cycle 4   -0.6  (13.4) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG)



15.  Secondary:   Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) 
[Units: Units on a scale]
Mean (Standard Deviation)
 
Cycle 1   
Participants Analyzed   341 
Cycle 1   -0.8  (0.9) 
Cycle 2   
Participants Analyzed   290 
Cycle 2   -0.9  (1) 
Cycle 3   
Participants Analyzed   218 
Cycle 3   -1  (1) 
Cycle 4   
Participants Analyzed   135 
Cycle 4   -1  (0.9) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended)



16.  Secondary:   Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed) 
[Units: Units on a scale]
Mean (Standard Deviation)
 
Cycle 1   
Participants Analyzed   340 
Cycle 1   -1  (1.2) 
Cycle 2   
Participants Analyzed   290 
Cycle 2   -1.1  (1) 
Cycle 3   
Participants Analyzed   218 
Cycle 3   -1.2  (1) 
Cycle 4   
Participants Analyzed   135 
Cycle 4   -1.1  (1.1) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed)



17.  Secondary:   Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4   [ Time Frame: Week 4 of each cycle ]

Measure Type Secondary
Measure Title Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4
Measure Description 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.
Time Frame Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 
[Units: Percentage of participants]
 
At least 1 grade reduction - Cycle 1   
Participants Analyzed   345 
At least 1 grade reduction - Cycle 1   56.2 
At least 1 grade reduction - Cycle 2   
Participants Analyzed   297 
At least 1 grade reduction - Cycle 2   57.6 
At least 1 grade reduction - Cycle 3   
Participants Analyzed   224 
At least 1 grade reduction - Cycle 3   60.7 
At least 1 grade reduction - Cycle 4   
Participants Analyzed   139 
At least 1 grade reduction - Cycle 4   66.9 
At least 2 grades reduction - Cycle 1   
Participants Analyzed   345 
At least 2 grades reduction - Cycle 1   18.3 
At least 2 grades reduction - Cycle 2   
Participants Analyzed   297 
At least 2 grades reduction - Cycle 2   23.2 
At least 2 grades reduction - Cycle 3   
Participants Analyzed   224 
At least 2 grades reduction - Cycle 3   23.2 
At least 2 grades reduction - Cycle 4   
Participants Analyzed   139 
At least 2 grades reduction - Cycle 4   22.3 

No statistical analysis provided for Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4



18.  Secondary:   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   [ Time Frame: Week 4 of each cycle ]

Measure Type Secondary
Measure Title 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
Measure Description 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 the percentage of subjects with at least a 1 grade reduction or 2 grades reduction in MAS score at Week 4.
Time Frame Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
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 
[Units: Percentage of participants]
 
At least 1 grade reduction - Cycle 1   
Participants Analyzed   345 
At least 1 grade reduction - Cycle 1   61.4 
At least 1 grade reduction - Cycle 2   
Participants Analyzed   297 
At least 1 grade reduction - Cycle 2   68.4 
At least 1 grade reduction - Cycle 3   
Participants Analyzed   224 
At least 1 grade reduction - Cycle 3   72.3 
At least 1 grade reduction - Cycle 4   
Participants Analyzed   139 
At least 1 grade reduction - Cycle 4   71.9 
At least 2 grades reduction - Cycle 1   
Participants Analyzed   345 
At least 2 grades reduction - Cycle 1   28.4 
At least 2 grades reduction - Cycle 2   
Participants Analyzed   297 
At least 2 grades reduction - Cycle 2   30.6 
At least 2 grades reduction - Cycle 3   
Participants Analyzed   224 
At least 2 grades reduction - Cycle 3   30.4 
At least 2 grades reduction - Cycle 4   
Participants Analyzed   139 
At least 2 grades reduction - Cycle 4   28.8 

No statistical analysis provided for 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



19.  Secondary:   Physician's Global Assessment (PGA) of Treatment Response at Week 4   [ Time Frame: Week 4 of each cycle ]

Measure Type Secondary
Measure Title Physician's Global Assessment (PGA) of Treatment Response at Week 4
Measure Description 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.
Time Frame Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Physician's Global Assessment (PGA) of Treatment Response at Week 4 
[Units: Units on a scale]
Mean (Standard Deviation)
 
Cycle 1   
Participants Analyzed   340 
Cycle 1   1.4  (1.1) 
Cycle 2   
Participants Analyzed   288 
Cycle 2   1.6  (1) 
Cycle 3   
Participants Analyzed   216 
Cycle 3   1.8  (1) 
Cycle 4   
Participants Analyzed   134 
Cycle 4   1.9  (1) 

No statistical analysis provided for Physician's Global Assessment (PGA) of Treatment Response at Week 4



20.  Secondary:   Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4   [ Time Frame: Week 4 of each cycle ]

Measure Type Secondary
Measure Title Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4
Measure Description 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.
Time Frame Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4 
[Units: Percentage of participants]
 
Cycle 1   
Participants Analyzed   345 
Cycle 1   83.8 
Cycle 2   
Participants Analyzed   297 
Cycle 2   86.2 
Cycle 3   
Participants Analyzed   224 
Cycle 3   89.3 
Cycle 4   
Participants Analyzed   139 
Cycle 4   89.9 

No statistical analysis provided for Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4



21.  Secondary:   Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended 
[Units: Degrees]
Mean (Standard Deviation)
 
Knee Extended - Cycle 1   
Participants Analyzed   340 
Knee Extended - Cycle 1   4.1  (10.6) 
Knee Extended - Cycle 2   
Participants Analyzed   290 
Knee Extended - Cycle 2   4.4  (10.6) 
Knee Extended - Cycle 3   
Participants Analyzed   218 
Knee Extended - Cycle 3   6  (11.4) 
Knee Extended - Cycle 4   
Participants Analyzed   135 
Knee Extended - Cycle 4   6.5  (10.9) 
Knee Flexed - Cycle 1   
Participants Analyzed   341 
Knee Flexed - Cycle 1   4.1  (10.7) 
Knee Flexed - Cycle 2   
Participants Analyzed   290 
Knee Flexed - Cycle 2   5  (10.3) 
Knee Flexed - Cycle 3   
Participants Analyzed   218 
Knee Flexed - Cycle 3   5.2  (10.9) 
Knee Flexed - Cycle 4   
Participants Analyzed   135 
Knee Flexed - Cycle 4   3.8  (9.8) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended



22.  Secondary:   Mean Change From Baseline to Week 4 in Lower Limb Pain   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in Lower Limb Pain
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Lower Limb Pain 
[Units: Units on a scale]
Mean (Standard Deviation)
 
Cycle 1   
Participants Analyzed   189 
Cycle 1   -0.7  (1.2) 
Cycle 2   
Participants Analyzed   160 
Cycle 2   -0.8  (1.2) 
Cycle 3   
Participants Analyzed   118 
Cycle 3   -0.9  (1.2) 
Cycle 4   
Participants Analyzed   75 
Cycle 4   -0.9  (1.2) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Lower Limb Pain



23.  Secondary:   Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) 
[Units: Units on a scale]
Mean (Standard Deviation)
 
PCS - Cycle 1   
Participants Analyzed   330 
PCS - Cycle 1   1.05  (7.5) 
PCS - Cycle 2   
Participants Analyzed   287 
PCS - Cycle 2   1.43  (7.67) 
PCS - Cycle 3   
Participants Analyzed   213 
PCS - Cycle 3   1.85  (7.01) 
PCS - Cycle 4   
Participants Analyzed   134 
PCS - Cycle 4   2.8  (6.65) 
MCS - Cycle 1   
Participants Analyzed   330 
MCS - Cycle 1   -1.13  (11.27) 
MCS - Cycle 2   
Participants Analyzed   287 
MCS - Cycle 2   -0.82  (12.7) 
MCS - Cycle 3   
Participants Analyzed   213 
MCS - Cycle 3   0.56  (12.24) 
MCS - Cycle 4   
Participants Analyzed   134 
MCS - Cycle 4   0.14  (13.23) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL)



24.  Secondary:   Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL 
[Units: Units on a scale]
Mean (Standard Deviation)
 
Pain/discomfort - Cycle 1   
Participants Analyzed   337 
Pain/discomfort - Cycle 1   -0.1  (1.0) 
Pain/discomfort - Cycle 2   
Participants Analyzed   288 
Pain/discomfort - Cycle 2   -0.2  (1.0) 
Pain/discomfort - Cycle 3   
Participants Analyzed   215 
Pain/discomfort - Cycle 3   -0.2  (1.0) 
Pain/discomfort - Cycle 4   
Participants Analyzed   133 
Pain/discomfort - Cycle 4   -0.4  (1.2) 
VAS - Cycle 1   
Participants Analyzed   336 
VAS - Cycle 1   2.8  (18.3) 
VAS - Cycle 2   
Participants Analyzed   286 
VAS - Cycle 2   3.8  (17.7) 
VAS - Cycle 3   
Participants Analyzed   215 
VAS - Cycle 3   4.4  (19.9) 
VAS - Cycle 4   
Participants Analyzed   133 
VAS - Cycle 4   5.5  (21.0) 

No statistical analysis provided for Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL



25.  Secondary:   Mean Change From Baseline to Week 4 in Walking Speed (WS)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in Walking Speed (WS)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Walking Speed (WS) 
[Units: Metres/second (m/s)]
Mean (Standard Deviation)
 
Comfortable WS, barefoot - Cycle 1   
Participants Analyzed   335 
Comfortable WS, barefoot - Cycle 1   0.07  (0.12) 
Comfortable WS, barefoot - Cycle 2   
Participants Analyzed   285 
Comfortable WS, barefoot - Cycle 2   0.08  (0.13) 
Comfortable WS, barefoot - Cycle 3   
Participants Analyzed   215 
Comfortable WS, barefoot - Cycle 3   0.08  (0.13) 
Comfortable WS, barefoot - Cycle 4   
Participants Analyzed   134 
Comfortable WS, barefoot - Cycle 4   0.09  (0.14) 
Comfortable WS, with shoes - Cycle 1   
Participants Analyzed   336 
Comfortable WS, with shoes - Cycle 1   0.06  (0.13) 
Comfortable WS, with shoes - Cycle 2   
Participants Analyzed   289 
Comfortable WS, with shoes - Cycle 2   0.07  (0.14) 
Comfortable WS, with shoes - Cycle 3   
Participants Analyzed   217 
Comfortable WS, with shoes - Cycle 3   0.08  (0.13) 
Comfortable WS, with shoes - Cycle 4   
Participants Analyzed   134 
Comfortable WS, with shoes - Cycle 4   0.08  (0.14) 
Maximal WS, barefoot - Cycle 1   
Participants Analyzed   336 
Maximal WS, barefoot - Cycle 1   0.07  (0.16) 
Maximal WS, barefoot - Cycle 2   
Participants Analyzed   286 
Maximal WS, barefoot - Cycle 2   0.08  (0.18) 
Maximal WS, barefoot - Cycle 3   
Participants Analyzed   215 
Maximal WS, barefoot - Cycle 3   0.09  (0.18) 
Maximal WS, barefoot - Cycle 4   
Participants Analyzed   134 
Maximal WS, barefoot - Cycle 4   0.1  (0.18) 
Maximal WS, with shoes - Cycle 1   
Participants Analyzed   335 
Maximal WS, with shoes - Cycle 1   0.07  (0.17) 
Maximal WS, with shoes - Cycle 2   
Participants Analyzed   286 
Maximal WS, with shoes - Cycle 2   0.09  (0.19) 
Maximal WS, with shoes - Cycle 3   
Participants Analyzed   217 
Maximal WS, with shoes - Cycle 3   0.09  (0.19) 
Maximal WS, with shoes - Cycle 4   
Participants Analyzed   134 
Maximal WS, with shoes - Cycle 4   0.1  (0.21) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Walking Speed (WS)



26.  Secondary:   Mean Change From Baseline to Week 4 in Step Length   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in Step Length
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Step Length 
[Units: M/step]
Mean (Standard Deviation)
 
Comfortable WS, barefoot - Cycle 1   
Participants Analyzed   335 
Comfortable WS, barefoot - Cycle 1   0.03  (0.06) 
Comfortable WS, barefoot - Cycle 2   
Participants Analyzed   285 
Comfortable WS, barefoot - Cycle 2   0.03  (0.09) 
Comfortable WS, barefoot - Cycle 3   
Participants Analyzed   215 
Comfortable WS, barefoot - Cycle 3   0.03  (0.08) 
Comfortable WS, barefoot - Cycle 4   
Participants Analyzed   134 
Comfortable WS, barefoot - Cycle 4   0.05  (0.09) 
Comfortable WS, with shoes - Cycle 1   
Participants Analyzed   336 
Comfortable WS, with shoes - Cycle 1   0.03  (0.07) 
Comfortable WS, with shoes - Cycle 2   
Participants Analyzed   289 
Comfortable WS, with shoes - Cycle 2   0.03  (0.08) 
Comfortable WS, with shoes - Cycle 3   
Participants Analyzed   217 
Comfortable WS, with shoes - Cycle 3   0.03  (0.08) 
Comfortable WS, with shoes - Cycle 4   
Participants Analyzed   134 
Comfortable WS, with shoes - Cycle 4   0.04  (0.09) 
Maximal WS, barefoot - Cycle 1   
Participants Analyzed   336 
Maximal WS, barefoot - Cycle 1   0.03  (0.08) 
Maximal WS, barefoot - Cycle 2   
Participants Analyzed   286 
Maximal WS, barefoot - Cycle 2   0.03  (0.09) 
Maximal WS, barefoot - Cycle 3   
Participants Analyzed   215 
Maximal WS, barefoot - Cycle 3   0.03  (0.09) 
Maximal WS, barefoot - Cycle 4   
Participants Analyzed   134 
Maximal WS, barefoot - Cycle 4   0.04  (0.09) 
Maximal WS, with shoes - Cycle 1   
Participants Analyzed   335 
Maximal WS, with shoes - Cycle 1   0.02  (0.08) 
Maximal WS, with shoes - Cycle 2   
Participants Analyzed   286 
Maximal WS, with shoes - Cycle 2   0.03  (0.09) 
Maximal WS, with shoes - Cycle 3   
Participants Analyzed   217 
Maximal WS, with shoes - Cycle 3   0.03  (0.09) 
Maximal WS, with shoes - Cycle 4   
Participants Analyzed   134 
Maximal WS, with shoes - Cycle 4   0.04  (0.1) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Step Length



27.  Secondary:   Mean Change From Baseline to Week 4 in Cadence   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in Cadence
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Cadence 
[Units: Steps/s]
Mean (Standard Deviation)
 
Comfortable WS, barefoot - Cycle 1   
Participants Analyzed   335 
Comfortable WS, barefoot - Cycle 1   0.08  (0.21) 
Comfortable WS, barefoot - Cycle 2   
Participants Analyzed   285 
Comfortable WS, barefoot - Cycle 2   0.08  (0.23) 
Comfortable WS, barefoot - Cycle 3   
Participants Analyzed   215 
Comfortable WS, barefoot - Cycle 3   0.08  (0.21) 
Comfortable WS, barefoot - Cycle 4   
Participants Analyzed   134 
Comfortable WS, barefoot - Cycle 4   0.07  (0.21) 
Comfortable WS, with shoes - Cycle 1   
Participants Analyzed   336 
Comfortable WS, with shoes - Cycle 1   0.07  (0.21) 
Comfortable WS, with shoes - Cycle 2   
Participants Analyzed   289 
Comfortable WS, with shoes - Cycle 2   0.08  (0.22) 
Comfortable WS, with shoes - Cycle 3   
Participants Analyzed   217 
Comfortable WS, with shoes - Cycle 3   0.08  (0.22) 
Comfortable WS, with shoes - Cycle 4   
Participants Analyzed   134 
Comfortable WS, with shoes - Cycle 4   0.07  (0.21) 
Maximal WS, barefoot - Cycle 1   
Participants Analyzed   336 
Maximal WS, barefoot - Cycle 1   0.07  (0.26) 
Maximal WS, barefoot - Cycle 2   
Participants Analyzed   286 
Maximal WS, barefoot - Cycle 2   0.08  (0.28) 
Maximal WS, barefoot - Cycle 3   
Participants Analyzed   215 
Maximal WS, barefoot - Cycle 3   0.09  (0.26) 
Maximal WS, barefoot - Cycle 4   
Participants Analyzed   134 
Maximal WS, barefoot - Cycle 4   0.11  (0.25) 
Maximal WS, with shoes - Cycle 1   
Participants Analyzed   335 
Maximal WS, with shoes - Cycle 1   0.07  (0.23) 
Maximal WS, with shoes - Cycle 2   
Participants Analyzed   286 
Maximal WS, with shoes - Cycle 2   0.09  (0.27) 
Maximal WS, with shoes - Cycle 3   
Participants Analyzed   217 
Maximal WS, with shoes - Cycle 3   0.09  (0.27) 
Maximal WS, with shoes - Cycle 4   
Participants Analyzed   134 
Maximal WS, with shoes - Cycle 4   0.09  (0.27) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Cadence



28.  Secondary:   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)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title 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)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
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) 
[Units: Degrees]
Mean (Standard Deviation)
 
Angle of arrest (XV1) – Cycle 1   
Participants Analyzed   341 
Angle of arrest (XV1) – Cycle 1   2.7  (7.9) 
Angle of arrest (XV1) – Cycle 2   
Participants Analyzed   290 
Angle of arrest (XV1) – Cycle 2   2.4  (7.8) 
Angle of arrest (XV1) – Cycle 3   
Participants Analyzed   218 
Angle of arrest (XV1) – Cycle 3   2.6  (8.9) 
Angle of arrest (XV1) – Cycle 4   
Participants Analyzed   135 
Angle of arrest (XV1) – Cycle 4   2.7  (8.4) 
Angle of catch (XV3) – Cycle 1   
Participants Analyzed   341 
Angle of catch (XV3) – Cycle 1   7.1  (10.6) 
Angle of catch (XV3) – Cycle 2   
Participants Analyzed   289 
Angle of catch (XV3) – Cycle 2   7.3  (11.1) 
Angle of catch (XV3) – Cycle 3   
Participants Analyzed   218 
Angle of catch (XV3) – Cycle 3   7.9  (12.2) 
Angle of catch (XV3) – Cycle 4   
Participants Analyzed   135 
Angle of catch (XV3) – Cycle 4   9.5  (12.4) 
Spasticity angle (X) – Cycle 1   
Participants Analyzed   341 
Spasticity angle (X) – Cycle 1   -4.4  (8.6) 
Spasticity angle (X) – Cycle 2   
Participants Analyzed   289 
Spasticity angle (X) – Cycle 2   -4.9  (9.2) 
Spasticity angle (X) – Cycle 3   
Participants Analyzed   218 
Spasticity angle (X) – Cycle 3   -5.4  (9.3) 
Spasticity angle (X) – Cycle 4   
Participants Analyzed   135 
Spasticity angle (X) – Cycle 4   -6.8  (9.2) 

No statistical analysis provided for 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)



29.  Secondary:   Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended) 
[Units: Units on a scale]
Mean (Standard Deviation)
 
Cycle 1   
Participants Analyzed   341 
Cycle 1   -0.5  (0.8) 
Cycle 2   
Participants Analyzed   290 
Cycle 2   -0.5  (0.7) 
Cycle 3   
Participants Analyzed   218 
Cycle 3   -0.5  (0.7) 
Cycle 4   
Participants Analyzed   135 
Cycle 4   -0.5  (0.8) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended)



30.  Secondary:   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)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title 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)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
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) 
[Units: Degrees]
Mean (Standard Deviation)
 
Angle of arrest (XV1) – Cycle 1   
Participants Analyzed   341 
Angle of arrest (XV1) – Cycle 1   1.9  (8.0) 
Angle of arrest (XV1) – Cycle 2   
Participants Analyzed   290 
Angle of arrest (XV1) – Cycle 2   2.8  (8.1) 
Angle of arrest (XV1) – Cycle 3   
Participants Analyzed   218 
Angle of arrest (XV1) – Cycle 3   2.6  (8.5) 
Angle of arrest (XV1) – Cycle 4   
Participants Analyzed   135 
Angle of arrest (XV1) – Cycle 4   2.4  (8.6) 
Angle of catch (XV3) – Cycle 1   
Participants Analyzed   341 
Angle of catch (XV3) – Cycle 1   6.9  (10.3) 
Angle of catch (XV3) – Cycle 2   
Participants Analyzed   289 
Angle of catch (XV3) – Cycle 2   7.5  (10.8) 
Angle of catch (XV3) – Cycle 3   
Participants Analyzed   218 
Angle of catch (XV3) – Cycle 3   7.8  (11.2) 
Angle of catch (XV3) – Cycle 4   
Participants Analyzed   135 
Angle of catch (XV3) – Cycle 4   8.8  (11.4) 
Spasticity angle (X) – Cycle 1   
Participants Analyzed   341 
Spasticity angle (X) – Cycle 1   -5.0  (10.0) 
Spasticity angle (X) – Cycle 2   
Participants Analyzed   289 
Spasticity angle (X) – Cycle 2   -4.7  (9.8) 
Spasticity angle (X) – Cycle 3   
Participants Analyzed   218 
Spasticity angle (X) – Cycle 3   -5.2  (9.6) 
Spasticity angle (X) – Cycle 4   
Participants Analyzed   135 
Spasticity angle (X) – Cycle 4   -6.4  (11.1) 

No statistical analysis provided for 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)



31.  Secondary:   Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed)   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed)
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed) 
[Units: Units on a scale]
Mean (Standard Deviation)
 
Cycle 1   
Participants Analyzed   341 
Cycle 1   -0.6  (0.8) 
Cycle 2   
Participants Analyzed   290 
Cycle 2   -0.6  (0.7) 
Cycle 3   
Participants Analyzed   218 
Cycle 3   -0.7  (0.8) 
Cycle 4   
Participants Analyzed   135 
Cycle 4   -0.7  (0.7) 

No statistical analysis provided for Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed)



32.  Secondary:   Use of Walking Aids/Orthoses at Baseline and Week 4   [ Time Frame: Baseline and Week 4 of each cycle ]

Measure Type Secondary
Measure Title Use of Walking Aids/Orthoses at Baseline and Week 4
Measure Description 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.
Time Frame Baseline and Week 4 of each cycle  

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

Reporting Groups
  Description
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 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).

Measured Values
   Total Dysport® 
Participants Analyzed   345 
Use of Walking Aids/Orthoses at Baseline and Week 4 
[Units: Participants]
Count of Participants
 
No Walking Aid at Baseline - Cycle 1   
Participants Analyzed   345 
No Walking Aid at Baseline - Cycle 1   101 
Walking Aid at Baseline - Cycle 1   
Participants Analyzed   345 
Walking Aid at Baseline - Cycle 1   244 
No Walking Aid at Week 4 - Cycle 1   
Participants Analyzed   341 
No Walking Aid at Week 4 - Cycle 1   99 
Walking Aid at Week 4 - Cycle 1   
Participants Analyzed   341 
Walking Aid at Week 4 - Cycle 1   242 
No Walking Aid at Baseline - Cycle 2   
Participants Analyzed   297 
No Walking Aid at Baseline - Cycle 2   84 
Walking Aid at Baseline - Cycle 2   
Participants Analyzed   297 
Walking Aid at Baseline - Cycle 2   213 
No Walking Aid at Week 4 - Cycle 2   
Participants Analyzed   292 
No Walking Aid at Week 4 - Cycle 2   80 
Walking Aid at Week 4 - Cycle 2   
Participants Analyzed   292 
Walking Aid at Week 4 - Cycle 2   212 
No Walking Aid at Baseline - Cycle 3   
Participants Analyzed   224 
No Walking Aid at Baseline - Cycle 3   56 
Walking Aid at Baseline - Cycle 3   
Participants Analyzed   224 
Walking Aid at Baseline - Cycle 3   168 
No Walking Aid at Week 4 - Cycle 3   
Participants Analyzed   206 
No Walking Aid at Week 4 - Cycle 3   59 
Walking Aid at Week 4 - Cycle 3   
Participants Analyzed   206 
Walking Aid at Week 4 - Cycle 3   147 
No Walking Aid at Baseline - Cycle 4   
Participants Analyzed   139 
No Walking Aid at Baseline - Cycle 4   40 
Walking Aid at Baseline - Cycle 4   
Participants Analyzed   139 
Walking Aid at Baseline - Cycle 4   99 
No Walking Aid at Week 4 - Cycle 4   
Participants Analyzed   97 
No Walking Aid at Week 4 - Cycle 4   33 
Walking Aid at Week 4 - Cycle 4   
Participants Analyzed   97 
Walking Aid at Week 4 - Cycle 4   64 

No statistical analysis provided for Use of Walking Aids/Orthoses at Baseline and Week 4




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Data is summarised according to total dose received at each corresponding cycle (i.e. including 1000 U and 1500 U Dysport® in lower limb during all cycles, as well as 1000 U in lower limb + 500 U Dysport® in upper limb during Cycles 3 and 4).


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Medical Director, Neurology,
Organization: Ipsen
e-mail: clinical.trials@ipsen.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT01251367     History of Changes
Other Study ID Numbers: Y-55-52120-142
First Submitted: November 25, 2010
First Posted: December 1, 2010
Results First Submitted: July 3, 2017
Results First Posted: November 9, 2017
Last Update Posted: November 9, 2017