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BOTOX® Treatment in Pediatric Lower Limb Spasticity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01603628
Recruitment Status : Completed
First Posted : May 22, 2012
Results First Posted : August 14, 2018
Last Update Posted : August 14, 2018
Sponsor:
Information provided by (Responsible Party):
Allergan

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Pediatrics
Muscle Spasticity
Cerebral Palsy
Interventions Biological: botulinum toxin Type A
Drug: Normal Saline (Placebo)
Enrollment 384
Recruitment Details  
Pre-assignment Details Pediatric participants with lower limb spasticity were randomized 1:1:1 to one of three treatment groups: BOTOX® 4 or 8 U/kg (unit per kilogram) or placebo.
Arm/Group Title BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Hide Arm/Group Description Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 units (U) per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT). Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT. Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT.
Period Title: Overall Study
Started 128 126 130
Safety Population: Received Treatment 128 126 128
Completed 125 123 128
Not Completed 3 3 2
Reason Not Completed
Personal Reasons             1             1             2
Protocol Violation             1             1             0
Lost to Follow-up             0             1             0
Other Miscellaneous Reason             1             0             0
Arm/Group Title BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo Total
Hide Arm/Group Description Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT). Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT. Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT. Total of all reporting groups
Overall Number of Baseline Participants 128 126 130 384
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 128 participants 126 participants 130 participants 384 participants
6.7  (3.90) 6.4  (3.58) 6.6  (3.89) 6.6  (3.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 128 participants 126 participants 130 participants 384 participants
Female
57
  44.5%
58
  46.0%
62
  47.7%
177
  46.1%
Male
71
  55.5%
68
  54.0%
68
  52.3%
207
  53.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 128 participants 126 participants 130 participants 384 participants
77
  60.2%
76
  60.3%
80
  61.5%
233
  60.7%
Black Number Analyzed 128 participants 126 participants 130 participants 384 participants
2
   1.6%
3
   2.4%
4
   3.1%
9
   2.3%
Asian Number Analyzed 128 participants 126 participants 130 participants 384 participants
42
  32.8%
35
  27.8%
38
  29.2%
115
  29.9%
Hispanic Number Analyzed 128 participants 126 participants 130 participants 384 participants
7
   5.5%
10
   7.9%
6
   4.6%
23
   6.0%
Other Not Specified Number Analyzed 128 participants 126 participants 130 participants 384 participants
0
   0.0%
1
   0.8%
3
   2.3%
4
   1.0%
Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score with Knee Extended   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 128 participants 126 participants 128 participants 382 participants
3.5  (0.52) 3.5  (0.53) 3.5  (0.50) 3.5  (0.52)
[1]
Measure Description: The MAS-B evaluates spasticity, grading the resistance encountered in the principal muscle group (elbow and wrist) by passively moving a limb through its range of motion at a specified velocity. The resistance encountered to passive stretch was graded on a 6-point scale: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5.
[2]
Measure Analysis Population Description: 2 participants in the Placebo arm are not included in the analysis.
1.Primary Outcome
Title Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score With Knee Extended at Weeks 4 and 6
Hide Description The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the principal muscle group (elbow and wrist) by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. A negative change from Baseline indicates improvement.
Time Frame Baseline (Day 1) to Weeks 4 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the mITT population, all randomized participants with a valid MAS-B baseline ankle score with knee extended and at least one post-baseline measurement at Weeks 2, 4, or 6 for the MAS-B of the ankle score with knee extended and the CGI by physician, with data available for analysis.
Arm/Group Title BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Hide Arm/Group Description:
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT).
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT.
Overall Number of Participants Analyzed 123 119 125
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.06  (0.071) -1.01  (0.072) -0.80  (0.071)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments MMRM including baseline MAS-B ankle score (knee extended) as a covariate and factors of age, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure where age is represented by stratification categories.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.453 to -0.063
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments MMRM including baseline MAS-B ankle score (knee extended) as a covariate and factors of age, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure where age is represented by stratification categories.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.405 to -0.018
Estimation Comments [Not Specified]
2.Primary Outcome
Title Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6
Hide Description The CGI of overall change (improvement or worsening) was assessed by the physician considering the participant's clinical condition and severity of side effects using a 9-point scale where: -4=very marked worsening to +4=very marked improvement. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis.
Time Frame Weeks 4 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the mITT population, all randomized participants with a valid MAS-B baseline ankle score with knee extended and at least one post-baseline measurement at Weeks 2, 4, or 6 for the MAS-B of the ankle score with knee extended and the CGI by physician, with data available for analysis.
Arm/Group Title BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Hide Arm/Group Description:
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT).
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT.
Overall Number of Participants Analyzed 123 118 124
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
1.65  (0.090) 1.49  (0.091) 1.36  (0.089)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments MMRM including baseline MAS-B ankle score (knee extended) as a covariate and factors of age, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure where age is represented by stratification categories.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.040 to 0.532
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.299
Comments MMRM including baseline MAS-B ankle score (knee extended) as a covariate and factors of age, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure where age is represented by stratification categories.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.115 to 0.374
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale
Hide Description Two functional goals, one active and one passive, were selected by the participant and family in consultation with the physician investigator and/or treating physical therapist relative to the lower limb impairment due to spasticity. The physician assessed the achievement of the goals using a 6-point scale: where -3=worse than start to +2=much more than expected: improvements clearly exceed the defined therapeutic goal. An Analysis of Covariance (ANCOVA) model was used for analysis.
Time Frame Weeks 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the mITT population, all randomized participants with a valid MAS-B baseline ankle score with knee extended and at least one post-baseline measurement at Weeks 2, 4, or 6 for the MAS-B of the ankle score with knee extended and the CGI by physician, with data available for analysis at the given time-point.
Arm/Group Title BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Hide Arm/Group Description:
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT).
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT.
Overall Number of Participants Analyzed 127 125 129
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Week 8, Active Goal Number Analyzed 121 participants 121 participants 127 participants
0.10  (0.108) -0.03  (0.108) -0.31  (0.105)
Week 8, Passive Goal Number Analyzed 120 participants 121 participants 127 participants
0.19  (0.115) 0.18  (0.114) -0.26  (0.111)
Week 12, Active Goal Number Analyzed 124 participants 123 participants 128 participants
0.37  (0.112) 0.09  (0.113) -0.12  (0.111)
Week 12, Passive Goal Number Analyzed 124 participants 123 participants 128 participants
0.40  (0.114) 0.27  (0.114) 0.00  (0.112)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Week 8, Active Goal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments ANCOVA model including baseline MAS-B ankle score with knee extended as a covariate and factors of age group, treatment group, study center and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.126 to 0.704
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Week 8, Active Goal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments ANCOVA model including baseline MAS-B ankle score with knee extended as a covariate and factors of age group, treatment group, study center and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.004 to 0.573
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Week 8, Passive Goal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments ANCOVA model including baseline MAS-B ankle score with knee extended as a covariate and factors of age group, treatment group, study center and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.145 to 0.756
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Week 8, Passive Goal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments ANCOVA model including baseline MAS-B ankle score with knee extended as a covariate and factors of age group, treatment group, study center and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.141 to 0.740
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Week 12, Active Goal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments ANCOVA model including baseline MAS-B ankle score with knee extended as a covariate and factors of age group, treatment group, study center and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.191 to 0.797
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Week 12, Active Goal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.153
Comments ANCOVA model including baseline MAS-B ankle score with knee extended as a covariate and factors of age group, treatment group, study center and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
-0.081 to 0.541
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Week 12, Passive Goal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments ANCOVA model including baseline MAS-B ankle score with knee extended as a covariate and factors of age group, treatment group, study center and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.100 to 0.711
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Week 12, Passive Goal
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments ANCOVA model including baseline MAS-B ankle score with knee extended as a covariate and factors of age group, treatment group, study center and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
-0.031 to 0.571
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Severity of Spasticity of the Ankle With Knee Extended and Knee Flexed (R2-R1) Calculated Using the Modified Tardieu Scale (MTS)
Hide Description The MTS measured the difference between slow and fast range of motion (R2-R1) and respective change from baseline to each posttreatment office visit. The MTS of the ankle was used to determine the passive range of movement at different movement velocities, V1 (as slow as possible) and V3 (as fast as possible) with the relative difference between a slow and fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. The investigator measured 2 joint angles by goniometer: the R1 angle which is the angle of catch after a fast velocity (V3) stretch and the R2 angle defined as the passive joint range of movement following a slow velocity (V1) stretch. The R2-R1 value indicated the level of the dynamic component of spasticity in the joint. The difference between R2 and R1 range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived. An Analysis of Covariance (ANCOVA) model was used for analysis.
Time Frame Baseline (Day 1) to Weeks 2, 4, 6, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the mITT population, all randomized participants with a valid MAS-B baseline ankle score with knee extended and at least one post-baseline measurement at Weeks 2, 4, or 6 for the MAS-B of the ankle score with knee extended and the CGI by physician, with data available for analysis at the given time-point.
Arm/Group Title BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Hide Arm/Group Description:
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT).
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT.
Overall Number of Participants Analyzed 127 125 129
Least Squares Mean (Standard Error)
Unit of Measure: degrees
Change from Baseline to Week 2 Number Analyzed 126 participants 124 participants 129 participants
-4.44  (1.023) -5.69  (1.024) -2.44  (1.0101)
Change from Baseline to Week 4 Number Analyzed 124 participants 121 participants 126 participants
-6.11  (1.134) -6.80  (1.135) -4.69  (1.121)
Change from Baseline to Week 6 Number Analyzed 126 participants 121 participants 126 participants
-6.65  (1.029) -7.23  (1.049) -3.32  (1.029)
Change from Baseline to Week 8 Number Analyzed 122 participants 123 participants 127 participants
-5.42  (1.317) -5.82  (1.308) -3.36  (1.291)
Change from Baseline to Week 12 Number Analyzed 125 participants 123 participants 128 participants
-4.59  (1.070) -3.07  (1.074) -1.98  (1.057)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Change from Baseline to Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.158
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.99
Confidence Interval (2-Sided) 95%
-4.768 to 0.779
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Change from Baseline to Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.25
Confidence Interval (2-Sided) 95%
-5.974 to -0.524
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Change from Baseline to Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.363
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.42
Confidence Interval (2-Sided) 95%
-4.489 to 1.648
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Change from Baseline to Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.171
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.11
Confidence Interval (2-Sided) 95%
-5.127 to 0.914
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Change from Baseline to Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.33
Confidence Interval (2-Sided) 95%
-6.143 to -0.525
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Change from Baseline to Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.92
Confidence Interval (2-Sided) 95%
-6.688 to -1.148
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Change from Baseline to Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.254
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.07
Confidence Interval (2-Sided) 95%
-5.621 to 1.491
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Change from Baseline to Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.165
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.46
Confidence Interval (2-Sided) 95%
-5.935 to 1.014
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection BOTOX® 8 U/kg, Placebo
Comments Change from Baseline to Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.61
Confidence Interval (2-Sided) 95%
-5.517 to 0.296
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection BOTOX® 4 U/kg, Placebo
Comments Change from Baseline to Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.451
Comments ANCOVA model including baseline MTS ankle score with knee extended as a covariate and factors of age group, treatment group, study center, and previous botulinum toxin exposure where age group is represented by stratification categories.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.09
Confidence Interval (2-Sided) 95%
-3.944 to 1.758
Estimation Comments [Not Specified]
Time Frame Baseline (Day 1) to the end of study (Week 12)
Adverse Event Reporting Description The Safety Population, all treated participants based on the treatment received, was used to determine the number of participants at risk for Serious Adverse Events and Adverse Events.
 
Arm/Group Title BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Hide Arm/Group Description Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT). Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT. Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT.
All-Cause Mortality
BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/128 (0.00%)   0/126 (0.00%)   0/128 (0.00%) 
Hide Serious Adverse Events
BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/128 (0.00%)   3/126 (2.38%)   4/128 (3.13%) 
Cardiac disorders       
Extrasystoles  1  0/128 (0.00%)  1/126 (0.79%)  0/128 (0.00%) 
Tachycardia  1  0/128 (0.00%)  1/126 (0.79%)  0/128 (0.00%) 
Infections and infestations       
Gastoeneteritis  1  0/128 (0.00%)  0/126 (0.00%)  1/128 (0.78%) 
Nervous system disorders       
Seizure  1  0/128 (0.00%)  1/126 (0.79%)  2/128 (1.56%) 
Radicular Pain  1  0/128 (0.00%)  0/126 (0.00%)  1/128 (0.78%) 
Respiratory, thoracic and mediastinal disorders       
Tonsillar hypertrophy  1  0/128 (0.00%)  1/126 (0.79%)  0/128 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BOTOX® 8 U/kg BOTOX® 4 U/kg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/128 (18.75%)   26/126 (20.63%)   35/128 (27.34%) 
General disorders       
Pyrexia  1  5/128 (3.91%)  8/126 (6.35%)  7/128 (5.47%) 
Infections and infestations       
Viral upper respiratory tract infection  1  12/128 (9.38%)  14/126 (11.11%)  22/128 (17.19%) 
Upper respiratory tract infection  1  8/128 (6.25%)  10/126 (7.94%)  9/128 (7.03%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Allergan
Phone: 714-246-4500
EMail: clinicaltrials@allergan.com
Layout table for additonal information
Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT01603628    
Other Study ID Numbers: 191622-111
2012-000042-35 ( EudraCT Number )
First Submitted: May 21, 2012
First Posted: May 22, 2012
Results First Submitted: June 12, 2018
Results First Posted: August 14, 2018
Last Update Posted: August 14, 2018