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Dysport® Adult Lower Limb Spasticity Study

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ClinicalTrials.gov Identifier: NCT01249404
Recruitment Status : Completed
First Posted : November 29, 2010
Results First Posted : October 17, 2017
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Leg Spasticity
Interventions Drug: Botulinum type A toxin (Dysport®)
Drug: Placebo
Enrollment 388
Recruitment Details The study was designed as a mutlicentre study and included 62 investigational centres in Australia, Belgium, the Czech Republic, France, Hungary, Italy, Poland, Portugal, Russia, Slovakia and the United States. Subjects were screened at 53 centres and in 52 centres subjects were randomised to receive study treatment.
Pre-assignment Details A total of 456 subjects were screened, 388 were enrolled into the study and randomised to 1 of 3 treatment groups.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description Subjects received intramuscular (i.m.) injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Period Title: Overall Study
Started 127 129 132
Completed 120 121 125
Not Completed 7 8 7
Reason Not Completed
Study treatment not received             0             1             2
No MAS Score at baseline and/or Week 4             2             0             2
Adverse Event             2             2             2
Withdrawal by Subject             2             2             0
Botulinum toxin (BTX) in upper limb             1             2             1
Non compliance to visit schedule             0             1             0
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo Total Title
Hide Arm/Group Description Subjects received i.m.injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. [Not Specified]
Overall Number of Baseline Participants 125 128 128 381
Hide Baseline Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a Modified Ashworth Scale (MAS) score in the gastrocnemius-soleus (GSC) assessed at baseline (pre-treatment) and at Week 4.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 125 participants 128 participants 128 participants 381 participants
53.2  (13.2) 53.3  (12.0) 51.4  (12.9) 52.6  (12.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 128 participants 128 participants 381 participants
Female
38
  30.4%
49
  38.3%
38
  29.7%
125
  32.8%
Male
87
  69.6%
79
  61.7%
90
  70.3%
256
  67.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 128 participants 128 participants 381 participants
Asian
3
   2.4%
4
   3.1%
3
   2.3%
10
   2.6%
Black or African American
5
   4.0%
13
  10.2%
5
   3.9%
23
   6.0%
Caucasian or White
116
  92.8%
109
  85.2%
119
  93.0%
344
  90.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.8%
0
   0.0%
1
   0.3%
Multiple
1
   0.8%
1
   0.8%
1
   0.8%
3
   0.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 128 participants 128 participants 381 participants
Hispanic or Latino
14
  11.2%
11
   8.6%
11
   8.6%
36
   9.4%
Not Hispanic or Latino
111
  88.8%
117
  91.4%
117
  91.4%
345
  90.6%
1.Primary Outcome
Title Least Squares Mean Change From Baseline to Week 4 in the MAS Score in the Gastrocnemius-soleus Complex (GSC) (Knee Extended)
Hide Description Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM)), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Week 4 is reported.
Time Frame Baseline and Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-0.6
(-0.8 to -0.5)
-0.8
(-0.9 to -0.7)
-0.5
(-0.7 to -0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 1000 U, Placebo
Comments The least squares mean change from baseline to Week 4 for MAS in the Dysport® 1000 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect analysis of covariance (ANCOVA) model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2859
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments LS Means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, BTX treatment status at baseline and centre as covariates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dysport® 1500 U, Placebo
Comments The least squares mean change from baseline to Week 4 for MAS in the Dysport® 1500 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect ANCOVA model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0091
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.5 to -0.1
Estimation Comments LS Means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, BTX treatment status at baseline and centre as covariates.
2.Secondary Outcome
Title Physician's Global Assesment (PGA) of Treatment Response at Week 4
Hide Description An assessment of overall treatment response was conducted at Weeks 4 and 12, and discretionary visits at Weeks 16, 20 and 24 and at end of study by an investigator who had not assessed the MAS. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a 9 point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. The mean PGA score at Week 4 is reported.
Time Frame At Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data at Week 4 are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 124 125 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.9
(0.7 to 1.1)
0.9
(0.7 to 1.1)
0.7
(0.5 to 0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 1000 U, Placebo
Comments The mean PGA at Week 4 in the Dysport® 1000 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect ANCOVA model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0640
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.0 to 0.5
Estimation Comments LS means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on visit results with treatment, BTX treatment status at baseline and centre as covariates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dysport® 1500 U, Placebo
Comments The mean PGA at Week 4 in the Dysport® 1500 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect ANCOVA model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0665
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.0 to 0.5
Estimation Comments LS means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on visit results with treatment, BTX treatment status at baseline and centre as covariates.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dysport® 1000 U, Placebo
Comments The LS mean rank values were back transformed to the original scale to give ranked PGA scores in an attempt to better normalise the data and restore power.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0466
Comments [Not Specified]
Method ANCOVA on rank PGA scores
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.2
Estimation Comments LS means for each treatment group and treatment comparisons and the p-values are obtained from an analysis of variance on visit results based on ranked values with treatment, BTX treatment status at baseline and centre as explanatory variables.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Dysport® 1500 U, Placebo
Comments The LS mean rank values were back transformed to the original scale to give ranked PGA scores in an attempt to better normalise the data and restore power.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0406
Comments [Not Specified]
Method ANCOVA on rank PGA scores
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.2
Estimation Comments LS means for each treatment group and treatment comparisons and the p-values are obtained from an analysis of variance on visit results based on ranked values with treatment, BTX treatment status at baseline and centre as explanatory variables.
3.Secondary Outcome
Title Least Squares Mean Change From Baseline to Week 4 in Comfortable Barefoot Walking Speed
Hide Description Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Week 4 is reported.
Time Frame Baseline and Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data at baseline and Week 4 are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 124 127 126
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/s
0.05
(0.03 to 0.07)
0.04
(0.03 to 0.06)
0.05
(0.03 to 0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport® 1000 U, Placebo
Comments The least squares mean change from baseline to Week 4 for barefoot comfortable walking speed in the Dysport® 1000 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect analysis of covariance (ANCOVA) model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.7247
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.02 to 0.03
Estimation Comments LS Means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, BTX treatment status at baseline and centre as covariates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dysport® 1500 U, Placebo
Comments The least squares mean change from baseline to Week 4 for barefoot comfortable walking speed in the Dysport® 1500 U and Placebo groups were compared using 2 contrast analyses within a single mixed effect ANCOVA model, controlling for the baseline values, the randomisation stratification factor (BTX treatment status at baseline) and the centre, all as fixed effects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.7266
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.03 to 0.02
Estimation Comments LS Means for each treatment group and treatment comparisons as well as the p-values are obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, BTX treatment status at baseline and centre as covariates.
4.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in MAS Score in the GSC (Knee Extended) at Weeks 1 and 12
Hide Description Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Weeks 1 and 12 are reported.
Time Frame Baseline and Weeks 1 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 1 Number Analyzed 123 participants 128 participants 128 participants
-0.4
(-0.6 to -0.3)
-0.5
(-0.6 to -0.4)
-0.4
(-0.5 to -0.2)
Week 12 Number Analyzed 120 participants 123 participants 122 participants
-0.4
(-0.5 to -0.2)
-0.6
(-0.7 to -0.4)
-0.4
(-0.5 to -0.2)
5.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in MAS Score in the Soleus (Knee Flexed) at Weeks 1, 4 and 12
Hide Description Muscle tone in the treated limb was assessed by MAS in the soleus (with the knee flexed) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 1 Number Analyzed 123 participants 128 participants 128 participants
-0.4
(-0.5 to -0.2)
-0.6
(-0.7 to -0.4)
-0.4
(-0.6 to -0.3)
Week 4 Number Analyzed 125 participants 128 participants 128 participants
-0.7
(-0.8 to -0.5)
-0.8
(-1.0 to -0.7)
-0.4
(-0.6 to -0.3)
Week 12 Number Analyzed 120 participants 123 participants 122 participants
-0.5
(-0.7 to -0.4)
-0.6
(-0.7 to -0.4)
-0.3
(-0.4 to -0.1)
6.Other Pre-specified Outcome
Title PGA of Treatment Response at Week 12
Hide Description An assessment of overall treatment response was conducted at Weeks 4 and 12, and discretionary visits at Weeks 16, 20 and 24 and at end of study by an investigator who had not assessed the MAS. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a 9 point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. The mean PGA scores at Week 12 are reported.
Time Frame At Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data at Week 12 are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 120 123 122
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.6
(0.4 to 0.7)
0.6
(0.4 to 0.8)
0.5
(0.3 to 0.7)
7.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Comfortable Barefoot Walking Speed at Weeks 1 and 12
Hide Description Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1 and 12 are reported.
Time Frame Baseline and Weeks 1 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/s
Week 1 Number Analyzed 123 participants 127 participants 127 participants
0.05
(0.04 to 0.07)
0.04
(0.02 to 0.05)
0.04
(0.02 to 0.05)
Week 12 Number Analyzed 120 participants 120 participants 120 participants
0.07
(0.05 to 0.09)
0.06
(0.04 to 0.08)
0.05
(0.03 to 0.07)
8.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12
Hide Description Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made with shoes, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/s
Week 1 Number Analyzed 122 participants 127 participants 127 participants
0.05
(0.03 to 0.07)
0.05
(0.03 to 0.07)
0.04
(0.02 to 0.05)
Week 4 Number Analyzed 124 participants 127 participants 127 participants
0.05
(0.03 to 0.07)
0.04
(0.02 to 0.06)
0.06
(0.04 to 0.08)
Week 12 Number Analyzed 119 participants 121 participants 122 participants
0.06
(0.04 to 0.08)
0.05
(0.03 to 0.07)
0.05
(0.03 to 0.07)
9.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Maximal Barefoot Walking Speed at Weeks 1, 4 and 12
Hide Description Maximal walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/s
Week 1 Number Analyzed 123 participants 127 participants 127 participants
0.06
(0.04 to 0.08)
0.05
(0.03 to 0.07)
0.05
(0.03 to 0.07)
Week 4 Number Analyzed 124 participants 127 participants 125 participants
0.07
(0.05 to 0.10)
0.04
(0.02 to 0.06)
0.05
(0.03 to 0.08)
Week 12 Number Analyzed 120 participants 120 participants 120 participants
0.09
(0.06 to 0.12)
0.06
(0.03 to 0.08)
0.06
(0.03 to 0.09)
10.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Maximal Walking Speed With Shoes at Weeks 1, 4 and 12
Hide Description Maximal walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made with shoes, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/s
Week 1 Number Analyzed 121 participants 127 participants 127 participants
0.05
(0.03 to 0.07)
0.05
(0.03 to 0.07)
0.04
(0.03 to 0.06)
Week 4 Number Analyzed 123 participants 127 participants 127 participants
0.05
(0.03 to 0.08)
0.04
(0.02 to 0.07)
0.05
(0.03 to 0.08)
Week 12 Number Analyzed 118 participants 121 participants 122 participants
0.07
(0.04 to 0.10)
0.05
(0.03 to 0.08)
0.05
(0.02 to 0.08)
11.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Cadence With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12
Hide Description Cadence was assessed during the 10-metre walking speed test at comfortable walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: steps/s
Week 1 Number Analyzed 122 participants 127 participants 127 participants
0.07
(0.04 to 0.10)
0.07
(0.04 to 0.10)
0.04
(0.01 to 0.07)
Week 4 Number Analyzed 124 participants 127 participants 127 participants
0.07
(0.04 to 0.10)
0.06
(0.03 to 0.10)
0.06
(0.02 to 0.09)
Week 12 Number Analyzed 119 participants 121 participants 122 participants
0.09
(0.05 to 0.12)
0.06
(0.03 to 0.09)
0.05
(0.01 to 0.08)
12.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Average Step Length With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12
Hide Description Average step length was assessed during the 10-metre walking speed test at comfortable walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/step
Week 1 Number Analyzed 122 participants 127 participants 127 participants
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.03)
Week 4 Number Analyzed 124 participants 127 participants 127 participants
0.02
(0.01 to 0.03)
0.01
(0.0 to 0.02)
0.03
(0.02 to 0.04)
Week 12 Number Analyzed 119 participants 121 participants 122 participants
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.04)
0.03
(0.01 to 0.04)
13.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Cadence With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12
Hide Description Cadence was assessed during the 10-metre walking speed test at comfortable walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: steps/s
Week 1 Number Analyzed 123 participants 127 participants 127 participants
0.10
(0.07 to 0.13)
0.05
(0.02 to 0.08)
0.05
(0.02 to 0.08)
Week 4 Number Analyzed 124 participants 127 participants 126 participants
0.08
(0.04 to 0.11)
0.06
(0.03 to 0.10)
0.06
(0.02 to 0.09)
Week 12 Number Analyzed 120 participants 120 participants 120 participants
0.12
(0.08 to 0.15)
0.08
(0.05 to 0.12)
0.07
(0.04 to 0.11)
14.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Average Step Length With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12
Hide Description Average step length was assessed during the 10-metre walking speed test at comfortable walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/step
Week 1 Number Analyzed 123 participants 127 participants 127 participants
0.02
(0.01 to 0.02)
0.02
(0.01 to 0.02)
0.01
(0.00 to 0.02)
Week 4 Number Analyzed 124 participants 127 participants 126 participants
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.03)
Week 12 Number Analyzed 120 participants 120 participants 120 participants
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.03)
15.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Cadence With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12
Hide Description Cadence was assessed during the 10-metre walking speed test at maximal walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: steps/s
Week 1 Number Analyzed 121 participants 127 participants 127 participants
0.06
(0.02 to 0.09)
0.07
(0.03 to 0.10)
0.04
(0.01 to 0.08)
Week 4 Number Analyzed 123 participants 127 participants 127 participants
0.05
(0.02 to 0.09)
0.05
(0.02 to 0.09)
0.05
(0.02 to 0.09)
Week 12 Number Analyzed 118 participants 121 participants 122 participants
0.08
(0.04 to 0.12)
0.07
(0.03 to 0.11)
0.04
(-0.00 to 0.08)
16.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Average Step Length With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12
Hide Description Average step length was assessed during the 10-metre walking speed test at maximal walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/step
Week 1 Number Analyzed 121 participants 127 participants 127 participants
0.02
(0.00 to 0.03)
0.01
(0.00 to 0.03)
0.02
(0.01 to 0.04)
Week 4 Number Analyzed 123 participants 127 participants 127 participants
0.02
(0.00 to 0.03)
0.02
(0.00 to 0.03)
0.02
(0.01 to 0.03)
Week 12 Number Analyzed 118 participants 121 participants 122 participants
0.02
(0.00 to 0.03)
0.02
(0.00 to 0.03)
0.03
(0.01 to 0.04)
17.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Cadence With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12
Hide Description Cadence was assessed during the 10-metre walking speed test at maximal walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: steps/s
Week 1 Number Analyzed 123 participants 127 participants 127 participants
0.07
(0.04 to 0.11)
0.05
(0.02 to 0.09)
0.06
(0.02 to 0.09)
Week 4 Number Analyzed 124 participants 127 participants 125 participants
0.08
(0.04 to 0.12)
0.05
(0.01 to 0.09)
0.07
(0.03 to 0.10)
Week 12 Number Analyzed 120 participants 120 participants 120 participants
0.12
(0.08 to 0.16)
0.08
(0.03 to 0.12)
0.06
(0.02 to 0.11)
18.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Average Step Length With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12
Hide Description Average step length was assessed during the 10-metre walking speed test at maximal walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: m/step
Week 1 Number Analyzed 123 participants 127 participants 127 participants
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.03)
0.02
(0.01 to 0.03)
Week 4 Number Analyzed 124 participants 127 participants 125 participants
0.02
(0.01 to 0.04)
0.02
(0.00 to 0.03)
0.02
(0.00 to 0.03)
Week 12 Number Analyzed 120 participants 120 participants 120 participants
0.02
(0.01 to 0.03)
0.02
(0.00 to 0.03)
0.02
(0.01 to 0.04)
19.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X)
Hide Description The Tardieu Scale in the GSC was used to assess spasticity with the knee extended. Assessments were made at slow (V1) and fast (V3) speeds of stretch. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest (XV1), either due to subject discomfort or a mechanical resistance. The same movement is repeated at a fast speed to determine the angle of catch and release (XV3). The spasticity angle (X) was calculated as the difference between XV1 and XV3. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Degrees
Week 1: Angle of Arrest (XV1) Number Analyzed 123 participants 127 participants 128 participants
2.4
(1.4 to 3.4)
2.3
(1.3 to 3.3)
1.7
(0.7 to 2.6)
Week 4: Angle of Arrest (XV1) Number Analyzed 125 participants 128 participants 127 participants
0.7
(-0.5 to 1.9)
1.4
(0.2 to 2.6)
1.3
(0.1 to 2.5)
Week 12: Angle of Arrest (XV1) Number Analyzed 120 participants 123 participants 122 participants
0.4
(-0.9 to 1.7)
0.4
(-0.9 to 1.6)
0.5
(-0.8 to 1.7)
Week 1: Angle of Catch (XV3) Number Analyzed 123 participants 128 participants 128 participants
5.1
(3.8 to 6.5)
5.4
(4.1 to 6.7)
3.2
(1.9 to 4.5)
Week 4: Angle of Catch (XV3) Number Analyzed 125 participants 128 participants 128 participants
4.8
(3.3 to 6.3)
5.3
(3.8 to 6.8)
3.4
(1.9 to 4.9)
Week 12: Angle of Catch (XV3) Number Analyzed 120 participants 123 participants 122 participants
3.0
(1.4 to 4.6)
2.9
(1.3 to 4.5)
2.6
(1.0 to 4.2)
Week 1: Spasticity Angle (X) Number Analyzed 123 participants 127 participants 128 participants
-2.5
(-3.7 to -1.3)
-3.2
(-4.4 to -2.0)
-1.7
(-2.8 to -0.5)
Week 4: Spasticity Angle (X) Number Analyzed 125 participants 128 participants 127 participants
-4.0
(-5.2 to -2.8)
-4.0
(-5.2 to -2.8)
-2.5
(-3.7 to -1.3)
Week 12: Spasticity Angle (X) Number Analyzed 120 participants 123 participants 122 participants
-2.4
(-3.7 to -1.1)
-2.8
(-4.0 to -1.5)
-2.3
(-3.5 to -1.0)
20.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Spasticity Grade (Y)
Hide Description The Tardieu Scale in the GSC was used to assess spasticity with the knee extended. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 = no resistance throughout passive movement; 1 = slight resistance throughout passive movement; 2 = clear catch at precise angle, interrupting passive movement, followed by release; 3 = fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release; 4 = unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline for spasticity grade at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 1 Number Analyzed 123 participants 127 participants 128 participants
-0.2
(-0.3 to -0.1)
-0.3
(-0.4 to -0.2)
-0.2
(-0.3 to -0.1)
Week 4 Number Analyzed 125 participants 128 participants 128 participants
-0.3
(-0.4 to -0.2)
-0.4
(-0.5 to -0.3)
-0.1
(-0.2 to -0.0)
Week 12 Number Analyzed 120 participants 123 participants 122 participants
-0.3
(-0.4 to -0.2)
-0.4
(-0.5 to -0.3)
-0.1
(-0.2 to -0.0)
21.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X)
Hide Description The Tardieu Scale in the soleus was used to assess spasticity with the knee flexed. Assessments were made at slow (V1) and fast (V3) speeds of stretch. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest (XV1), either due to subject discomfort or a mechanical resistance. The same movement is repeated at a fast speed to determine the angle of catch and release (XV3). The spasticity angle (X) was calculated as the difference between XV1 and XV3. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Degrees
Week 1: Angle of Arrest (XV1) Number Analyzed 123 participants 127 participants 128 participants
2.2
(1.2 to 3.2)
1.5
(0.6 to 2.5)
1.4
(0.4 to 2.3)
Week 4: Angle of Arrest (XV1) Number Analyzed 125 participants 128 participants 128 participants
1.2
(0.1 to 2.3)
1.0
(-0.1 to 2.1)
1.3
(0.2 to 2.4)
Week 12: Angle of Arrest (XV1) Number Analyzed 120 participants 123 participants 122 participants
0.4
(-0.7 to 1.5)
0.1
(-1.0 to 1.1)
0.0
(-1.0 to 1.1)
Week 1: Angle of Catch (XV3) Number Analyzed 123 participants 128 participants 128 participants
4.1
(2.5 to 5.8)
4.1
(2.5 to 5.8)
2.5
(0.9 to 4.1)
Week 4: Angle of Catch (XV3) Number Analyzed 125 participants 128 participants 128 participants
5.1
(3.5 to 6.6)
4.9
(3.4 to 6.4)
2.9
(1.5 to 4.4)
Week 12: Angle of Catch (XV3) Number Analyzed 120 participants 123 participants 122 participants
4.0
(2.5 to 5.4)
3.7
(2.2 to 5.1)
2.7
(1.2 to 4.1)
Week 1: Spasticity Angle (X) Number Analyzed 123 participants 127 participants 128 participants
-1.7
(-3.1 to -0.2)
-2.8
(-4.2 to -1.4)
-1.3
(-2.6 to -0.1)
Week 4: Spasticity Angle (X) Number Analyzed 125 participants 128 participants 128 participants
-3.6
(-4.9 to -2.4)
-4.2
(-5.5 to -3.0)
-1.8
(-3.1 to -0.6)
Week 12: Spasticity Angle (X) Number Analyzed 120 participants 123 participants 122 participants
-3.3
(-4.6 to -2.1)
-3.9
(-5.2 to -2.7)
-2.8
(-4.1 to -1.6)
22.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Spasticity Grade (Y)
Hide Description The Tardieu Scale in the soleus was used to assess spasticity with the knee flexed. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 = no resistance throughout passive movement; 1 = slight resistance throughout passive movement; 2 = clear catch at precise angle, interrupting passive movement, followed by release; 3 = fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release; 4 = unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline for spasticity grade at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 1 Number Analyzed 123 participants 127 participants 128 participants
-0.2
(-0.3 to -0.1)
-0.3
(-0.4 to -0.2)
-0.1
(-0.2 to -0.0)
Week 4 Number Analyzed 125 participants 128 participants 128 participants
-0.5
(-0.6 to -0.3)
-0.5
(-0.6 to -0.4)
-0.1
(-0.2 to -0.0)
Week 12 Number Analyzed 120 participants 123 participants 122 participants
-0.4
(-0.5 to -0.3)
-0.4
(-0.5 to -0.3)
-0.1
(-0.2 to -0.0)
23.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed)
Hide Description Range of active dorsiflexion of the ankle joint, both with the knee flexed (90°) and extended (measured by goniometry) was used to assess treatment response. The measurements were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits when needed at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Degrees
Week 1: Knee Extended Number Analyzed 123 participants 128 participants 128 participants
1.7
(0.4 to 3.0)
2.4
(1.1 to 3.7)
1.1
(-0.2 to 2.4)
Week 4: Knee Extended Number Analyzed 125 participants 128 participants 127 participants
1.5
(-0.2 to 3.1)
3.7
(2.0 to 5.3)
1.6
(-0.1 to 3.2)
Week 12: Knee Extended Number Analyzed 119 participants 123 participants 122 participants
1.1
(-0.5 to 2.7)
2.0
(0.5 to 3.6)
1.7
(0.1 to 3.2)
Week 1: Knee Flexed Number Analyzed 123 participants 127 participants 128 participants
3.0
(1.5 to 4.4)
2.0
(0.6 to 3.4)
1.9
(0.5 to 3.3)
Week 4: Knee Flexed Number Analyzed 125 participants 128 participants 128 participants
2.9
(1.4 to 4.5)
3.3
(1.8 to 4.9)
2.7
(1.2 to 4.2)
Week 12: Knee Flexed Number Analyzed 119 participants 123 participants 121 participants
2.0
(0.4 to 3.6)
1.4
(-0.1 to 2.9)
1.8
(0.2 to 3.3)
24.Other Pre-specified Outcome
Title Least Squares Mean Change From Baseline in Lower Limb Pain at Weeks 1, 4 and 12
Hide Description The intensity of lower limb pain was evaluated using the Scale of Pain Intensity (SPIN) which provided a pictorial representation of pain in a 6-point graphic scale with the degree of red shading inside a circle representing the intensity of pain. The bottom and top of the scale are anchored by two extremes: ‘no pain’ (circle with no red shading and scored as 0) and ‘pain as bad as it could be’ (circle completely red and scored as 5), marked with either verbal or visual cues. The intervening points are represented by red circles increasing proportionally in size. The subject marks the circle that best indicates their pain intensity. The SPIN assessments were obtained prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits when needed at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Weeks 1, 4 and 12 are reported.
Time Frame Baseline and Weeks 1, 4 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomised subjects who received at least 1 injection of study medication and who had a MAS score in the GSC assessed at baseline (pre-treatment) and at Week 4. Only subjects with data available at each timepoint presented are included in the analysis.
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description:
Subjects received i.m. injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA).
Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
Overall Number of Participants Analyzed 125 128 128
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 1 Number Analyzed 121 participants 127 participants 128 participants
-0.3
(-0.4 to -0.1)
-0.1
(-0.3 to 0.0)
-0.2
(-0.3 to -0.0)
Week 4 Number Analyzed 122 participants 126 participants 128 participants
-0.1
(-0.3 to -0.1)
-0.2
(-0.4 to 0.0)
-0.1
(-0.3 to 0.1)
Week 12 Number Analyzed 118 participants 121 participants 122 participants
-0.2
(-0.4 to 0.0)
-0.1
(-0.3 to 0.1)
0.1
(-0.1 to 0.3)
Time Frame From baseline up to Week 24 +/- 2 weeks.
Adverse Event Reporting Description Adverse event (AE) data is reported as treatment emergent AEs; an AE was reported as emergent if it arose (i.e. started or worsened in severity) after the subject received study medication and were monitored from the time that the subject gave informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports. The safety population consisted of all randomised subjects who received at least 1 injection of study medication.
 
Arm/Group Title Dysport® 1000 U Dysport® 1500 U Placebo
Hide Arm/Group Description Subjects received intramuscular (i.m.) injections of Dysport® 1000 Units (U) (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). Subjects received i.m. injections of Dysport® 1500 U (maximum total dose) into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). Subjects received i.m. injections of placebo into the soleus muscle and gastrocnemius (medial and/or lateral) muscle and at least one of the distal or proximal muscles of the leg on Day 1 of the single treatment cycle.
All-Cause Mortality
Dysport® 1000 U Dysport® 1500 U Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Dysport® 1000 U Dysport® 1500 U Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/127 (3.94%)      5/128 (3.91%)      7/130 (5.38%)    
Blood and lymphatic system disorders       
Anaemia  1  0/127 (0.00%)  0 1/128 (0.78%)  1 0/130 (0.00%)  0
Cardiac disorders       
Sinus tachycardia  1  1/127 (0.79%)  1 0/128 (0.00%)  0 0/130 (0.00%)  0
Congenital, familial and genetic disorders       
Atrial septal defect  1  0/127 (0.00%)  0 0/128 (0.00%)  0 1/130 (0.77%)  1
General disorders       
Chest pain  1  0/127 (0.00%)  0 0/128 (0.00%)  0 1/130 (0.77%)  1
Infections and infestations       
Appendicitis  1  0/127 (0.00%)  0 1/128 (0.78%)  1 0/130 (0.00%)  0
Post procedural infection  1  0/127 (0.00%)  0 0/128 (0.00%)  0 1/130 (0.77%)  1
Pneumonia  1  0/127 (0.00%)  0 0/128 (0.00%)  0 1/130 (0.77%)  1
Injury, poisoning and procedural complications       
Humerus fracture  1  1/127 (0.79%)  1 0/128 (0.00%)  0 0/130 (0.00%)  0
Femoral neck fracture  1  0/127 (0.00%)  0 0/128 (0.00%)  0 1/130 (0.77%)  1
Femur Fracture  1  0/127 (0.00%)  0 1/128 (0.78%)  1 0/130 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Muscular weakness  1  0/127 (0.00%)  0 1/128 (0.78%)  1 0/130 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Pancreatic carcinoma  1  1/127 (0.79%)  1 0/128 (0.00%)  0 0/130 (0.00%)  0
Nervous system disorders       
Cerebrovascular accident  1  0/127 (0.00%)  0 1/128 (0.78%)  1 0/130 (0.00%)  0
Convulsion  1  2/127 (1.57%)  2 0/128 (0.00%)  0 1/130 (0.77%)  1
Ischaemic stroke  1  0/127 (0.00%)  0 0/128 (0.00%)  0 1/130 (0.77%)  1
Loss of consciousness  1 [1]  0/127 (0.00%)  0 0/128 (0.00%)  0 1/130 (0.77%)  1
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1 [2]  0/127 (0.00%)  0 1/128 (0.78%)  1 1/130 (0.77%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
[1]
Death
[2]
Death (in placebo subject)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dysport® 1000 U Dysport® 1500 U Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/127 (17.32%)      21/128 (16.41%)      11/130 (8.46%)    
Injury, poisoning and procedural complications       
Fall  1  12/127 (9.45%)  14 8/128 (6.25%)  9 4/130 (3.08%)  8
Musculoskeletal and connective tissue disorders       
Pain in extremity  1  7/127 (5.51%)  7 8/128 (6.25%)  9 3/130 (2.31%)  3
Muscular weakness  1  3/127 (2.36%)  3 7/128 (5.47%)  8 4/130 (3.08%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
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
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT01249404     History of Changes
Other Study ID Numbers: Y-55-52120-140
2009-015868-34 ( EudraCT Number )
First Submitted: November 25, 2010
First Posted: November 29, 2010
Results First Submitted: July 3, 2017
Results First Posted: October 17, 2017
Last Update Posted: December 11, 2017