Cerebral Palsy, Muscle Spasticity, Pediatrics, Stroke
Conditions
Brief summary
This study will evaluate the safety and efficacy of BOTOX® (botulinum toxin Type A) in pediatric patients with upper limb spasticity.
Interventions
BIOLOGICALbotulinum toxin Type A
Intramuscular injections of botulinum toxin Type A into specified muscles of the upper limb on Day 1.
DRUGNormal Saline (Placebo)
Intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Minimum weight of 10 kg/22 lb * Upper limb spasticity due to cerebral palsy or stroke
Exclusion criteria
* Muscular dystrophy, myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or mitochondrial disease * Uncontrolled epilepsy * Botulinum Toxin therapy of any serotype for any condition within the last 6 months * Previous surgical treatment of the study limb (except tendon lengthening), or planned surgery of the study limb during the study * Previous casting of the study limb for spasticity within 6 months or with a dynamic splint within 3 months, or planned casting or dynamic splinting for spasticity of the study limb or affected lower limb during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group at Weeks 4 and 6 | Baseline (Day 1) to Weeks 4 and 6 | 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. |
| Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6 | Weeks 4 and 6 | 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 MMRM model was used for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in MAS-B Score of the Finger Flexor Muscle Group at Weeks 4 and 6 | Baseline (Day 1) to Weeks 4 and 6 | The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the finger flexor muscle group 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. An Analysis of Covariance (ANCOVA) model was used for analysis. A negative change from Baseline indicates improvement. |
| Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 8 and 12 | 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 ANCOVA model was used for analysis. |
| Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Baseline (Day 1) to Week 6 | 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 a fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. At each visit, 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 slow (R2) and fast (R1) range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived. |
Countries
Canada, Hungary, Philippines, Poland, Russia, South Korea, Thailand, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
Pediatric participants with upper limb spasticity were randomized 1:1:1 to one of three treatment groups: BOTOX® 3 or 6 U/kg (unit per kilogram) or placebo.
Participants by arm
| Arm | Count |
|---|---|
| BOTOX® 6 U/kg Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT). | 77 |
| BOTOX® 3 U/kg Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 U/kg into specified muscles of the upper limb on Day 1. Participants received weekly OT. | 78 |
| Placebo Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT. | 80 |
| Total | 235 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Personal Reasons | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | BOTOX® 6 U/kg | BOTOX® 3 U/kg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 7.6 years STANDARD_DEVIATION 3.66 | 8.3 years STANDARD_DEVIATION 4.48 | 7.8 years STANDARD_DEVIATION 4.06 | 7.9 years STANDARD_DEVIATION 4.07 |
| Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group Change | 3.3 score on a scale STANDARD_DEVIATION 0.45 | 3.3 score on a scale STANDARD_DEVIATION 0.45 | 3.3 score on a scale STANDARD_DEVIATION 0.44 | 3.3 score on a scale STANDARD_DEVIATION 0.45 |
| Race/Ethnicity, Customized Asian | 19 Participants | 27 Participants | 18 Participants | 64 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 4 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Other Unspecified | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 51 Participants | 42 Participants | 51 Participants | 144 Participants |
| Sex: Female, Male Female | 27 Participants | 36 Participants | 32 Participants | 95 Participants |
| Sex: Female, Male Male | 50 Participants | 42 Participants | 48 Participants | 140 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 78 | 0 / 79 |
| other Total, other adverse events | 15 / 77 | 12 / 78 | 17 / 79 |
| serious Total, serious adverse events | 3 / 77 | 1 / 78 | 1 / 79 |
Outcome results
Primary
Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group at Weeks 4 and 6
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
Population: Participants from the Modified Intent-to treat (mITT) population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® 6 U/kg | Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group at Weeks 4 and 6 | -1.87 score on a scale | Standard Error 0.102 |
| BOTOX® 3 U/kg | Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group at Weeks 4 and 6 | -1.92 score on a scale | Standard Error 0.101 |
| Placebo | Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group at Weeks 4 and 6 | -1.21 score on a scale | Standard Error 0.102 |
p-value: <0.00195% CI: [-0.938, -0.379]Mixed Model Repeated Measures (MMRM)
p-value: <0.00195% CI: [-0.992, -0.426]MMRM
Primary
Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6
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 MMRM model was used for analysis.
Time frame: Weeks 4 and 6
Population: Participants from the m ITT population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis at the given time-point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® 6 U/kg | Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6 | 1.87 score on a scale | Standard Error 0.108 |
| BOTOX® 3 U/kg | Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6 | 1.88 score on a scale | Standard Error 0.108 |
| Placebo | Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6 | 1.66 score on a scale | Standard Error 0.108 |
p-value: 0.15595% CI: [-0.082, 0.511]MMRM
p-value: 0.14795% CI: [-0.079, 0.523]MMRM
Secondary
Average Change From Baseline in MAS-B Score of the Finger Flexor Muscle Group at Weeks 4 and 6
The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the finger flexor muscle group 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. An Analysis of Covariance (ANCOVA) model was used for analysis. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) to Weeks 4 and 6
Population: Participants from the mITT population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis at the given time-point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® 6 U/kg | Average Change From Baseline in MAS-B Score of the Finger Flexor Muscle Group at Weeks 4 and 6 | -1.41 score on a scale | Standard Error 0.184 |
| BOTOX® 3 U/kg | Average Change From Baseline in MAS-B Score of the Finger Flexor Muscle Group at Weeks 4 and 6 | -1.46 score on a scale | Standard Error 0.169 |
| Placebo | Average Change From Baseline in MAS-B Score of the Finger Flexor Muscle Group at Weeks 4 and 6 | -1.02 score on a scale | Standard Error 0.17 |
p-value: 0.11195% CI: [-0.861, 0.091]ANCOVA
p-value: 0.07895% CI: [-0.933, 0.051]ANCOVA
Secondary
Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS)
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 a fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. At each visit, 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 slow (R2) and fast (R1) range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived.
Time frame: Baseline (Day 1) to Week 6
Population: Participants from the mITT population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 4, Wrist | -22.97 degrees | Standard Error 4.965 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 6, Wrist | -24.33 degrees | Standard Error 5.036 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 8, Wrist | -20.87 degrees | Standard Error 4.621 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 2, Elbow | 33.27 degrees | Standard Error 5.246 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 12, Wrist | -16.87 degrees | Standard Error 4.927 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 8, Elbow | 31.17 degrees | Standard Error 4.238 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 4, Elbow | 31.49 degrees | Standard Error 4.116 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 12, Elbow | 14.69 degrees | Standard Error 3.828 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 2, Wrist | -15.72 degrees | Standard Error 4.096 |
| BOTOX® 6 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 6, Elbow | 37.62 degrees | Standard Error 4.372 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 4, Elbow | 28.63 degrees | Standard Error 4.16 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 8, Elbow | 23.14 degrees | Standard Error 4.188 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 6, Wrist | -18.47 degrees | Standard Error 4.641 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 6, Elbow | 28.00 degrees | Standard Error 4.268 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 2, Elbow | 29.58 degrees | Standard Error 5.268 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 8, Wrist | -18.90 degrees | Standard Error 4.307 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 2, Wrist | -24.20 degrees | Standard Error 3.831 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 12, Elbow | 14.06 degrees | Standard Error 3.775 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 12, Wrist | -15.14 degrees | Standard Error 4.607 |
| BOTOX® 3 U/kg | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 4, Wrist | -25.43 degrees | Standard Error 4.557 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 12, Wrist | -1.62 degrees | Standard Error 4.509 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 2, Elbow | 21.17 degrees | Standard Error 5.602 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 4, Elbow | 16.78 degrees | Standard Error 4.272 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 6, Elbow | 16.65 degrees | Standard Error 4.408 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 8, Elbow | 15.92 degrees | Standard Error 4.276 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 12, Elbow | 10.19 degrees | Standard Error 3.854 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 2, Wrist | -9.60 degrees | Standard Error 3.877 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 4, Wrist | -12.33 degrees | Standard Error 4.447 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 6, Wrist | -7.22 degrees | Standard Error 4.57 |
| Placebo | Change From Baseline in Severity of Spasticity of the Principal Muscle Group (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | Change from Baseline to Week 8, Wrist | -3.16 degrees | Standard Error 4.303 |
Comparison: Change from Baseline to Week 2, Elbowp-value: 0.11795% CI: [-3.089, 27.293]ANCOVA
Comparison: Change from Baseline to Week 2, Elbowp-value: 0.27395% CI: [-6.717, 23.527]ANCOVA
Comparison: Change from Baseline to Week 4, Elbowp-value: 0.01595% CI: [2.958, 26.458]ANCOVA
Comparison: Change from Baseline to Week 4, Elbowp-value: 0.04695% CI: [0.203, 23.504]ANCOVA
Comparison: Change from Baseline to Week 6, Elbowp-value: <0.00195% CI: [8.801, 33.137]ANCOVA
Comparison: Change from Baseline to Week 6, Elbowp-value: 0.06495% CI: [-0.662, 23.362]ANCOVA
Comparison: Change from Baseline to Week 8, Elbowp-value: 0.01395% CI: [3.317, 27.178]ANCOVA
Comparison: Change from Baseline to Week 8, Elbowp-value: 0.22595% CI: [-4.488, 18.934]ANCOVA
Comparison: Change from Baseline to Week 12, Elbowp-value: 0.40995% CI: [-6.239, 15.236]ANCOVA
Comparison: Change from Baseline to Week 12, Elbowp-value: 0.4795% CI: [-6.69, 14.419]ANCOVA
Comparison: Change from Baseline to Week 2, Wristp-value: 0.26395% CI: [-16.962, 4.706]ANCOVA
Comparison: Change from Baseline to Week 2, Wristp-value: 0.01295% CI: [-25.846, -3.36]ANCOVA
Comparison: Change from Baseline to Week 4, Wristp-value: 0.09895% CI: [-23.277, 1.996]ANCOVA
Comparison: Change from Baseline to Week 4, Wristp-value: 0.05195% CI: [-26.26, 0.068]ANCOVA
Comparison: Change from Baseline to Week 6, Wristp-value: 0.0195% CI: [-30.031, -4.189]ANCOVA
Comparison: Change from Baseline to Week 6, Wristp-value: 0.09895% CI: [-24.622, 2.131]ANCOVA
Comparison: Change from Baseline to Week 8, Wristp-value: 0.00595% CI: [-29.888, -5.537]ANCOVA
Comparison: Change from Baseline to Week 8, Wristp-value: 0.01595% CI: [-28.293, -3.194]ANCOVA
Comparison: Change from Baseline to Week 12, Wristp-value: 0.0295% CI: [-28.01, -2.492]ANCOVA
Comparison: Change from Baseline to Week 12, Wristp-value: 0.04695% CI: [-26.797, -0.243]ANCOVA
Secondary
Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale
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 ANCOVA model was used for analysis.
Time frame: Week 8 and 12
Population: Participants from the mITT population, all randomized participants with a valid MAS-B baseline score and at least one post-baseline measurement at weeks 2, 4, or 6 for the MAS-B of the principal muscle group and the CGI by physician, with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX® 6 U/kg | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 12, Passive Goal | 0.71 score on a scale | Standard Error 0.143 |
| BOTOX® 6 U/kg | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 8, Active Goal | 0.11 score on a scale | Standard Error 0.148 |
| BOTOX® 6 U/kg | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 8, Passive Goal | 0.30 score on a scale | Standard Error 0.146 |
| BOTOX® 6 U/kg | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 12, Active Goal | 0.49 score on a scale | Standard Error 0.143 |
| BOTOX® 3 U/kg | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 12, Active Goal | 0.26 score on a scale | Standard Error 0.139 |
| BOTOX® 3 U/kg | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 12, Passive Goal | 0.31 score on a scale | Standard Error 0.139 |
| BOTOX® 3 U/kg | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 8, Passive Goal | 0.23 score on a scale | Standard Error 0.146 |
| BOTOX® 3 U/kg | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 8, Active Goal | 0.12 score on a scale | Standard Error 0.148 |
| Placebo | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 12, Active Goal | 0.52 score on a scale | Standard Error 0.139 |
| Placebo | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 8, Active Goal | 0.21 score on a scale | Standard Error 0.148 |
| Placebo | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 8, Passive Goal | 0.06 score on a scale | Standard Error 0.146 |
| Placebo | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Week 12, Passive Goal | 0.11 score on a scale | Standard Error 0.139 |
Comparison: Week 8, Active Goalp-value: 0.63695% CI: [-0.498, 0.305]ANCOVA
Comparison: Week 8, Active Goalp-value: 0.65895% CI: [-0.502, 0.318]ANCOVA
Comparison: Week 8, Passive Goalp-value: 0.24395% CI: [-0.162, 0.635]ANCOVA
Comparison: Week 8, Passive Goalp-value: 0.41295% CI: [-0.237, 0.576]ANCOVA
Comparison: Week 12, Active Goalp-value: 0.90495% CI: [-0.408, 0.361]ANCOVA
Comparison: Week 12, Active Goalp-value: 0.295% CI: [-0.641, 0.135]ANCOVA
Comparison: Week 12, Passive Goalp-value: 0.00395% CI: [0.21, 0.978]ANCOVA
Comparison: Week 12, Passive Goalp-value: 0.32795% CI: [-0.194, 0.58]ANCOVA