Lower Limb Spasticity Due to Cerebral Palsy
Conditions
Brief summary
The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg(s) are effective in treating children/adolescents (age 2-17 years) with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.
Interventions
DRUGIncobotulinumtoxinA (16 Units per kg body weight)
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl); Total volume 8.0 mL; 400 units; Mode of administration: intramuscular injection into spastic muscles.
DRUGIncobotulinumtoxinA (12 Units per kg body weight)
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl); Total volume 8.0 mL; 300 units; Mode of administration: intramuscular injection into spastic muscles.
DRUGIncobotulinumtoxinA (4 Units per kg body weight)
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl); Total volume 8.0 mL; 100 units; Mode of administration: intramuscular injection into spastic muscles.
Sponsors
Merz Pharmaceuticals GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Female or male subject of 2 to 17 years of age (inclusive). * Uni- or bilateral cerebral palsy with clinical need for uni- or bilateral LL injections with BoNT for the treatment of spasticity. * Ashworth Scale \[AS\] score ≥2 in plantar flexors (at least unilaterally). * Clinical need for a total dose of 16 U/kg BW NT 201 (maximum of 400 U) for the treatment of LL spasticity according to the clinical judgment of the investigator.
Exclusion criteria
* Fixed contracture defined as severe restriction of the range of joint movement on passive stretch or predominant forms of muscle hypertonia other than spasticity (e.g., dystonia) in the target limb(s). * Surgery on pes equinus on side(s) intended to be treated with BoNT injections in this study within 12 months prior to Screening Visit (V1), in the screening period or planned for the time of participation in this study. * Hip flexion requiring BoNT injection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC) | Baseline, Week 4 | The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (= no increase in tone) to 4 (=limb rigid in flexion or extension). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and Week 4 resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
| Co-primary Variable: Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle | Baseline, Week 4 | This variable is classified as co-primary to satisfy a Food and Drug Administration (FDA) request. The GICS-PF scale is a 7-Point Likert Scale for the assessment of the functional change due to treatment of plantar flexor spasticity only. Ranges from +3 (very much improved function) to -3 (very much worse function). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Baseline to Week 8 and 12 of 1st IC and 2nd IC (Week 20-44 and 24-48) | The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
| Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40) | The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. KF = Knee Flexors; TA = Thigh Adductors; w = week. |
| Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Baseline to Week 4, 8, and 12 of 1st IC and 2nd IC (Week 16-40, 20-44 and 24-48) | The Modified Tardieu Scale (MTS) assesses spastic muscle tone by subtraction of two angles measured at different conditions of passive muscle stretch. R2 is the angle of passive range of motion with a passive movement at slow speed. R1 is the angle where a catch-and-release or clonus can be triggered at the fastest possible speed. Score values represent the measured (R2-R1) difference, i.e. the dynamic tone component of the examined muscle(s). Decreases of (R2-R1) represent reductions in the dynamic component of spasticity, i.e. improvement of dynamic muscle spasticity. Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the model used for comparison and are therefore provided separately for each comparison. |
| Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40) | The Global Impression of Change Scales (GICS) are global outcomes to assess the impression of change due to treatment. GICS were assessed by the investigator, by the participant (if feasible) and by parents'/caregiver (if applicable). GICS are 7-Point Likert Scales ranging from +3 (very much improved function) to -3 (very much worse function). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
| Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40) | The GICS are global outcomes to assess the impression of change due to treatment. GICS were assessed by the investigator, by the participant (if feasible) and by parents'/caregiver (if applicable). GICS are 7-Point Likert Scales ranging from +3 (very much improved function) to -3 (very much worse function). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
| Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Baseline to Week 12-36 of 1st IC and 2nd IC (End of study = Week 24-72) | The GMFM-66 is a standardized observational 66-item instrument designed and validated to measure change in gross motor function over time in participants with cerebral palsy. Score values represent the total GMFM-66 score. Total GMFM scores range from 0 (worst) to 100 (best). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
| Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Baseline to Week 4, 8, and 12 of 1st IC and 2nd IC (Week 16-40, 20-44 and 24-48) | The QPS is a patient-reported outcome for children and adolescents (2-17 years) with cerebral palsy on spasticity-related pain. Pain intensity (from participants) and pain frequency (from parent/caregiver) to be assessed with 'Questionnaire on Pain caused by Spasticity \[QPS\]'. The QPS Total Score for pain intensity ranges from 0 ('No Hurt') to 10 ('Hurt Worst'). The QPS Total Score for the observed pain frequency ranges from 0 (Never) to 4 (Always). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
| Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Baseline, Week 4 of 1st IC and Week 16-40 of 2nd IC | The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
| Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Up to End of study visit (Week 24-72) | Treatment-emergent Adverse Events (TEAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected. |
| Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | Up to End of study visit (Week 24-72) | Adverse Events (AE's) occurring after treatment that were thought to possibly indicate toxin spread throughout the trial conduct are defined as AE's of Special Interests. Values reported here refer to the number of participants affected. |
| Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | Up to End of study visit (Week 24-72) | Treatment-emergent Serious Adverse Events (TESAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected. |
| Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | Up to End of study visit (Week 24-72) | Treatment-emergent Adverse Events (TEAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected. |
| Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Up to End of study visit (Week 24-72) | Treatment-emergent Adverse Events (TEAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected. |
| Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Up to End of study visit (Week 24-72) | Treatment-emergent Adverse Events (TEAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected. |
| Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | Up to End of study visit (Week 24-72) | Treatment-emergent Adverse Events (TEASs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected. |
| Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle | Baseline up to Week 24-72 | — |
| Change From Baseline in the AS Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the Second Injection Cycle | Baseline to Week 4 of 2nd IC (Week 16-40) | The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and Week 16-40 resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. |
Countries
Austria, Czechia, Estonia, France, Germany, Israel, Poland, Romania, Russia, Slovakia, South Korea, Spain, Turkey (Türkiye), Ukraine
Participant flow
Pre-assignment details
The Safety Evaluation Set (SES) is the subset of all participants treated with study medication at least once.
Participants by arm
| Arm | Count |
|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles. | 156 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles. | 77 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles. | 78 |
| Total | 311 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Other | 3 | 1 | 3 |
| Overall Study | Physician Decision | 1 | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 3 |
Baseline characteristics
| Characteristic | High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 156 Participants | 77 Participants | 78 Participants | 311 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.4 years STANDARD_DEVIATION 3.9 | 6.6 years STANDARD_DEVIATION 3.8 | 7.1 years STANDARD_DEVIATION 4.6 | 6.6 years STANDARD_DEVIATION 4.1 |
| Sex: Female, Male Female | 83 Participants | 44 Participants | 42 Participants | 169 Participants |
| Sex: Female, Male Male | 73 Participants | 33 Participants | 36 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 156 | 10 / 77 | 15 / 78 |
| serious Total, serious adverse events | 7 / 156 | 1 / 77 | 6 / 78 |
Outcome results
Primary
Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC)
The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (= no increase in tone) to 4 (=limb rigid in flexion or extension). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and Week 4 resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline, Week 4
Population: FAS population is subset in the SES for whom primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) \[participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the 1st IC) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC) | Week 4 of 1st IC (high versus low) | -0.7 Units on a scale | Standard Error 0.061 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC) | Week 4 of 1st IC (mid versus low) | -0.7 Units on a scale | Standard Error 0.089 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC) | Week 4 of 1st IC (high versus low) | -0.66 Units on a scale | Standard Error 0.084 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC) | Week 4 of 1st IC (mid versus low) | -0.66 Units on a scale | Standard Error 0.088 |
p-value: =0.6595% CI: [-0.23, 0.14]Mixed Model Repeated Measure
p-value: =0.74195% CI: [-0.26, 0.18]Mixed Model Repeated Measure
Primary
Co-primary Variable: Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle
This variable is classified as co-primary to satisfy a Food and Drug Administration (FDA) request. The GICS-PF scale is a 7-Point Likert Scale for the assessment of the functional change due to treatment of plantar flexor spasticity only. Ranges from +3 (very much improved function) to -3 (very much worse function). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline, Week 4
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Co-primary Variable: Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle | Week 4 of 1st IC (high versus low) | 1.53 Units on a scale | Standard Error 0.059 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Co-primary Variable: Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle | Week 4 of 1st IC (mid versus low) | 1.38 Units on a scale | Standard Error 0.092 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Co-primary Variable: Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle | Week 4 of 1st IC (high versus low) | 1.37 Units on a scale | Standard Error 0.081 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Co-primary Variable: Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle | Week 4 of 1st IC (mid versus low) | 1.32 Units on a scale | Standard Error 0.09 |
p-value: =0.07595% CI: [-0.02, 0.34]Mixed Model Repeated Measure
p-value: =0.60395% CI: [-0.16, 0.27]Mixed Model Repeated Measure
Secondary
Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC)
The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline, Week 4 of 1st IC and Week 16-40 of 2nd IC
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Week 4 of 1st IC (high versus low) | -0.76 Units on a scale | Standard Error 0.073 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Week 4 of 2nd IC (high versus low) | -0.95 Units on a scale | Standard Error 0.077 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Week 4 of 1st IC (mid versus low) | -0.6 Units on a scale | Standard Error 0.105 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Week 4 of 2nd IC (mid versus low) | -0.85 Units on a scale | Standard Error 0.124 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Week 4 of 1st IC (mid versus low) | -0.58 Units on a scale | Standard Error 0.108 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Week 4 of 2nd IC (mid versus low) | -0.76 Units on a scale | Standard Error 0.123 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Week 4 of 2nd IC (high versus low) | -0.74 Units on a scale | Standard Error 0.106 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) | Week 4 of 1st IC (high versus low) | -0.61 Units on a scale | Standard Error 0.104 |
Secondary
Change From Baseline in the AS Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the Second Injection Cycle
The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and Week 16-40 resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline to Week 4 of 2nd IC (Week 16-40)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the Second Injection Cycle | Week 4 of 2nd IC (high versus low) | -0.89 Units on a scale | Standard Error 0.061 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the Second Injection Cycle | Week 4 of 2nd IC (mid versus low) | -1.03 Units on a scale | Standard Error 0.094 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the Second Injection Cycle | Week 4 of 2nd IC (high versus low) | -0.82 Units on a scale | Standard Error 0.082 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change From Baseline in the AS Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the Second Injection Cycle | Week 4 of 2nd IC (mid versus low) | -0.85 Units on a scale | Standard Error 0.091 |
Secondary
Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle
The QPS is a patient-reported outcome for children and adolescents (2-17 years) with cerebral palsy on spasticity-related pain. Pain intensity (from participants) and pain frequency (from parent/caregiver) to be assessed with 'Questionnaire on Pain caused by Spasticity \[QPS\]'. The QPS Total Score for pain intensity ranges from 0 ('No Hurt') to 10 ('Hurt Worst'). The QPS Total Score for the observed pain frequency ranges from 0 (Never) to 4 (Always). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline to Week 4, 8, and 12 of 1st IC and 2nd IC (Week 16-40, 20-44 and 24-48)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 4 of 2nd IC (high versus low) | -0.53 Units on a scale | Standard Error 0.26 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 4 of 1st IC (high versus low) | -0.66 Units on a scale | Standard Error 0.198 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 8 of 1st IC (high versus low) | -0.48 Units on a scale | Standard Error 0.069 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 12, 2nd IC (high versus low) | -0.49 Units on a scale | Standard Error 0.085 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 8 of 2nd IC (high versus low) | -0.55 Units on a scale | Standard Error 0.08 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 4 of 2nd IC (high versus low) | -0.54 Units on a scale | Standard Error 0.078 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 8 of 2nd IC (high versus low) | -0.78 Units on a scale | Standard Error 0.272 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 4 of 1st IC (high versus low) | -0.44 Units on a scale | Standard Error 0.067 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, Week12, 1st IC (high versus low) | -0.44 Units on a scale | Standard Error 0.071 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 12 of 1st IC (high versus low) | -0.42 Units on a scale | Standard Error 0.207 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 12 of 2nd IC (high versus low) | -0.34 Units on a scale | Standard Error 0.299 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 8 of 1st IC (high versus low) | -0.6 Units on a scale | Standard Error 0.228 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 12, 1st IC (mid versus low) | -0.21 Units on a scale | Standard Error 0.095 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 8 of 2nd IC (mid versus low) | -1.56 Units on a scale | Standard Error 0.312 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 12 of 2nd IC (mid versus low) | -1.37 Units on a scale | Standard Error 0.333 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 4 of 2nd IC (mid versus low) | -0.59 Units on a scale | Standard Error 0.111 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 8 of 2nd IC (mid versus low) | -0.54 Units on a scale | Standard Error 0.119 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 4 of 2nd IC (mid versus low) | -1.36 Units on a scale | Standard Error 0.347 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 12, 2nd IC (mid versus low) | -0.52 Units on a scale | Standard Error 0.128 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 4 of 1st IC (mid versus low) | -1.02 Units on a scale | Standard Error 0.301 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 8 of 1st IC (mid versus low) | -0.94 Units on a scale | Standard Error 0.299 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 12 of 1st IC (mid versus low) | -1.14 Units on a scale | Standard Error 0.253 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 4 of 1st IC (mid versus low) | -0.31 Units on a scale | Standard Error 0.094 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 8 of 1st IC (mid versus low) | -0.29 Units on a scale | Standard Error 0.092 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 12, 2nd IC (mid versus low) | -0.33 Units on a scale | Standard Error 0.121 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 4 of 2nd IC (high versus low) | -1.03 Units on a scale | Standard Error 0.289 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 4 of 1st IC (high versus low) | -1.32 Units on a scale | Standard Error 0.23 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 8 of 2nd IC (high versus low) | -1.16 Units on a scale | Standard Error 0.302 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 4 of 1st IC (mid versus low) | -1.61 Units on a scale | Standard Error 0.31 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 12, 1st IC (mid versus low) | -0.3 Units on a scale | Standard Error 0.095 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 8 of 1st IC (high versus low) | -0.93 Units on a scale | Standard Error 0.265 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 8 of 1st IC (mid versus low) | -0.33 Units on a scale | Standard Error 0.091 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 8 of 1st IC (mid versus low) | -1.06 Units on a scale | Standard Error 0.308 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 8 of 2nd IC (high versus low) | -0.47 Units on a scale | Standard Error 0.104 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 12 of 1st IC (high versus low) | -1.13 Units on a scale | Standard Error 0.241 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 8 of 2nd IC (mid versus low) | -1.61 Units on a scale | Standard Error 0.315 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 12 of 1st IC (mid versus low) | -1.47 Units on a scale | Standard Error 0.261 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 4 of 2nd IC (high versus low) | -0.47 Units on a scale | Standard Error 0.102 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 4 of 1st IC (high versus low) | -0.49 Units on a scale | Standard Error 0.089 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, Week12, 1st IC (high versus low) | -0.37 Units on a scale | Standard Error 0.095 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 4 of 1st IC (mid versus low) | -0.34 Units on a scale | Standard Error 0.093 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 12 of 2nd IC (high versus low) | -0.97 Units on a scale | Standard Error 0.333 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 4 of 2nd IC (mid versus low) | -0.46 Units on a scale | Standard Error 0.105 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 12 of 2nd IC (mid versus low) | -1.4 Units on a scale | Standard Error 0.336 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 8 of 2nd IC (mid versus low) | -0.44 Units on a scale | Standard Error 0.113 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Participant, w 4 of 2nd IC (mid versus low) | -1.53 Units on a scale | Standard Error 0.351 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 12, 2nd IC (high versus low) | -0.4 Units on a scale | Standard Error 0.112 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle | Parent/Caregiver, w 8 of 1st IC (high versus low) | -0.47 Units on a scale | Standard Error 0.092 |
Secondary
Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle
The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. KF = Knee Flexors; TA = Thigh Adductors; w = week.
Time frame: Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Knee Flexors, Week 4 of 1st IC (high versus low) | -0.6 Units on a scale | Standard Error 0.18 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Knee Flexors, Week 4 of 2nd IC (high versus low) | -0.64 Units on a scale | Standard Error 0.173 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Thigh Adductors,Week 4 of 1st IC (high versus low) | -0.61 Units on a scale | Standard Error 0.287 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Thigh Adductors,Week 4 of 2nd IC (high versus low) | NA Units on a scale | — |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Knee Flexors, Week 4 of 2nd IC (mid versus low) | -0.31 Units on a scale | Standard Error 0.269 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Thigh Adductors,Week 4 of 1st IC (mid versus low) | NA Units on a scale | — |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Knee Flexors, Week 4 of 1st IC (mid versus low) | -0.07 Units on a scale | Standard Error 0.285 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Thigh Adductors,Week 4 of 2nd IC (mid versus low) | NA Units on a scale | — |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Thigh Adductors,Week 4 of 1st IC (mid versus low) | NA Units on a scale | — |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Thigh Adductors,Week 4 of 2nd IC (mid versus low) | NA Units on a scale | — |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Knee Flexors, Week 4 of 1st IC (high versus low) | -0.39 Units on a scale | Standard Error 0.214 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Thigh Adductors,Week 4 of 2nd IC (high versus low) | NA Units on a scale | — |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Knee Flexors, Week 4 of 1st IC (mid versus low) | -0.32 Units on a scale | Standard Error 0.204 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Knee Flexors, Week 4 of 2nd IC (high versus low) | -0.79 Units on a scale | Standard Error 0.2 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Knee Flexors, Week 4 of 2nd IC (mid versus low) | -0.67 Units on a scale | Standard Error 0.19 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle | Thigh Adductors,Week 4 of 1st IC (high versus low) | -0.76 Units on a scale | Standard Error 0.506 |
Secondary
Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle
The Ashworth Scale (AS) is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline to Week 8 and 12 of 1st IC and 2nd IC (Week 20-44 and 24-48)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 1st IC (high versus low) | -0.62 Units on a scale | Standard Error 0.059 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 1st IC (high versus low) | -0.43 Units on a scale | Standard Error 0.056 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 2nd IC (high versus low) | -0.76 Units on a scale | Standard Error 0.058 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 2nd IC (high versus low) | -0.57 Units on a scale | Standard Error 0.058 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 1st IC (mid versus low) | -0.45 Units on a scale | Standard Error 0.086 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 2nd IC (mid versus low) | -0.92 Units on a scale | Standard Error 0.092 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 1st IC (mid versus low) | -0.74 Units on a scale | Standard Error 0.088 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 2nd IC (mid versus low) | -0.64 Units on a scale | Standard Error 0.088 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 2nd IC (mid versus low) | -0.79 Units on a scale | Standard Error 0.09 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 2nd IC (mid versus low) | -0.68 Units on a scale | Standard Error 0.085 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 1st IC (high versus low) | -0.69 Units on a scale | Standard Error 0.08 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 2nd IC (high versus low) | -0.65 Units on a scale | Standard Error 0.079 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 1st IC (mid versus low) | -0.69 Units on a scale | Standard Error 0.086 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 1st IC (high versus low) | -0.58 Units on a scale | Standard Error 0.077 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 1st IC (mid versus low) | -0.59 Units on a scale | Standard Error 0.085 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 2nd IC (high versus low) | -0.76 Units on a scale | Standard Error 0.079 |
Secondary
Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit
The GMFM-66 is a standardized observational 66-item instrument designed and validated to measure change in gross motor function over time in participants with cerebral palsy. Score values represent the total GMFM-66 score. Total GMFM scores range from 0 (worst) to 100 (best). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline to Week 12-36 of 1st IC and 2nd IC (End of study = Week 24-72)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Week 12-36 of 1st IC (high versus low) | 1.23 Units on a scale | Standard Error 0.288 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Week 12-36 of 2nd IC (high versus low) | 2.31 Units on a scale | Standard Error 0.359 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Week 12-36 of 1st IC (mid versus low) | 1.14 Units on a scale | Standard Error 0.448 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Week 12-36 of 2nd IC (mid versus low) | 3.1 Units on a scale | Standard Error 0.542 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Week 12-36 of 1st IC (mid versus low) | 1.49 Units on a scale | Standard Error 0.445 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Week 12-36 of 2nd IC (mid versus low) | 2.59 Units on a scale | Standard Error 0.539 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Week 12-36 of 2nd IC (high versus low) | 2.46 Units on a scale | Standard Error 0.488 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit | Week 12-36 of 1st IC (high versus low) | 1.64 Units on a scale | Standard Error 0.392 |
Secondary
Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle
The Modified Tardieu Scale (MTS) assesses spastic muscle tone by subtraction of two angles measured at different conditions of passive muscle stretch. R2 is the angle of passive range of motion with a passive movement at slow speed. R1 is the angle where a catch-and-release or clonus can be triggered at the fastest possible speed. Score values represent the measured (R2-R1) difference, i.e. the dynamic tone component of the examined muscle(s). Decreases of (R2-R1) represent reductions in the dynamic component of spasticity, i.e. improvement of dynamic muscle spasticity. Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the model used for comparison and are therefore provided separately for each comparison.
Time frame: Baseline to Week 4, 8, and 12 of 1st IC and 2nd IC (Week 16-40, 20-44 and 24-48)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 4 of 2nd IC (high versus low) | -4.72 Angle | Standard Error 1.173 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 1st IC (high versus low) | -3.1 Angle | Standard Error 0.848 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 2nd IC (high versus low) | -4.27 Angle | Standard Error 0.968 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 4 of 1st IC (high versus low) | -2.38 Angle | Standard Error 0.897 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 2nd IC (high versus low) | -4.72 Angle | Standard Error 1.065 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 1st IC (high versus low) | -3.15 Angle | Standard Error 0.921 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 1st IC (mid versus low) | -1.74 Angle | Standard Error 1.393 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 4 of 1st IC (mid versus low) | -0.88 Angle | Standard Error 1.389 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 1st IC (mid versus low) | -0.07 Angle | Standard Error 1.231 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 4 of 2nd IC (mid versus low) | -3.24 Angle | Standard Error 1.773 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 2nd IC (mid versus low) | -2.97 Angle | Standard Error 1.634 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 2nd IC (mid versus low) | -2.12 Angle | Standard Error 1.519 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 1st IC (high versus low) | -2.63 Angle | Standard Error 1.267 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 4 of 2nd IC (high versus low) | -3.83 Angle | Standard Error 1.594 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 2nd IC (high versus low) | -5.68 Angle | Standard Error 1.298 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 4 of 2nd IC (mid versus low) | -3.6 Angle | Standard Error 1.713 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 4 of 1st IC (mid versus low) | -2.47 Angle | Standard Error 1.367 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 2nd IC (high versus low) | -4.25 Angle | Standard Error 1.44 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 2nd IC (mid versus low) | -5.45 Angle | Standard Error 1.455 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 2nd IC (mid versus low) | -4.04 Angle | Standard Error 1.575 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 8 of 1st IC (mid versus low) | -2.56 Angle | Standard Error 1.372 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 1st IC (high versus low) | -2.67 Angle | Standard Error 1.157 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 4 of 1st IC (high versus low) | -2.56 Angle | Standard Error 1.231 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle | Week 12 of 1st IC (mid versus low) | -2.59 Angle | Standard Error 1.213 |
Secondary
Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle
The Global Impression of Change Scales (GICS) are global outcomes to assess the impression of change due to treatment. GICS were assessed by the investigator, by the participant (if feasible) and by parents'/caregiver (if applicable). GICS are 7-Point Likert Scales ranging from +3 (very much improved function) to -3 (very much worse function). Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from MMRM (Mixed Model Repeated Measurement) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Investigator, 2nd IC (high versus low) | 1.46 Units on a scale | Standard Error 0.071 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Parent/Caregiver, 1st IC (high versus low) | 1.53 Units on a scale | Standard Error 0.068 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Parent/Caregiver, 2nd IC (high versus low) | 1.45 Units on a scale | Standard Error 0.076 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Participants, 1st IC (high versus low) | 1.72 Units on a scale | Standard Error 0.205 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Investigator, 1st IC (high versus low) | 1.5 Units on a scale | Standard Error 0.056 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Participants, 2nd IC (high versus low) | 1.53 Units on a scale | Standard Error 0.21 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Parent/Caregiver, 1st IC (mid versus low) | 1.26 Units on a scale | Standard Error 0.107 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Participants, 1st IC (mid versus low) | 1.17 Units on a scale | Standard Error 0.203 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Investigator, 2nd IC (mid versus low) | 1.56 Units on a scale | Standard Error 0.11 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Participants, 2nd IC (mid versus low) | 1.44 Units on a scale | Standard Error 0.276 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Parent/Caregiver, 2nd IC (mid versus low) | 1.67 Units on a scale | Standard Error 0.115 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Investigator, 1st IC (mid versus low) | 1.36 Units on a scale | Standard Error 0.087 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Parent/Caregiver, 2nd IC (mid versus low) | 1.4 Units on a scale | Standard Error 0.109 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Investigator, 1st IC (high versus low) | 1.35 Units on a scale | Standard Error 0.076 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Investigator, 1st IC (mid versus low) | 1.33 Units on a scale | Standard Error 0.086 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Participants, 1st IC (high versus low) | 1.64 Units on a scale | Standard Error 0.223 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Participants, 1st IC (mid versus low) | 1.3 Units on a scale | Standard Error 0.216 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Parent/Caregiver, 1st IC (high versus low) | 1.43 Units on a scale | Standard Error 0.092 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Parent/Caregiver, 1st IC (mid versus low) | 1.39 Units on a scale | Standard Error 0.105 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Investigator, 2nd IC (high versus low) | 1.38 Units on a scale | Standard Error 0.096 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Investigator, 2nd IC (mid versus low) | 1.46 Units on a scale | Standard Error 0.104 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Participants, 2nd IC (mid versus low) | 1.53 Units on a scale | Standard Error 0.283 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Parent/Caregiver, 2nd IC (high versus low) | 1.34 Units on a scale | Standard Error 0.101 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle | Participants, 2nd IC (high versus low) | 1.66 Units on a scale | Standard Error 0.224 |
Secondary
Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle
The GICS are global outcomes to assess the impression of change due to treatment. GICS were assessed by the investigator, by the participant (if feasible) and by parents'/caregiver (if applicable). GICS are 7-Point Likert Scales ranging from +3 (very much improved function) to -3 (very much worse function). For participants with bilateral pes equinus, the body side for primary efficacy analysis i.e. primary body side was decided by investigator at screening and was kept throughout the entire study. For participants with unilateral treatment, the treated body side was kept throughout the entire study. Values represent least square (LS) mean differences between baseline and the respective week (w) resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Week 4 of 1st IC (high versus low) | 1.53 Units on a scale | Standard Error 0.059 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Week 4 of 2nd IC (high versus low) | 1.43 Units on a scale | Standard Error 0.073 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Week 4 of 1st IC (mid versus low) | 1.38 Units on a scale | Standard Error 0.092 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Week 4 of 2nd IC (mid versus low) | 1.54 Units on a scale | Standard Error 0.11 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Week 4 of 1st IC (mid versus low) | 1.32 Units on a scale | Standard Error 0.09 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Week 4 of 2nd IC (mid versus low) | 1.48 Units on a scale | Standard Error 0.103 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Week 4 of 2nd IC (high versus low) | 1.38 Units on a scale | Standard Error 0.098 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle | Week 4 of 1st IC (high versus low) | 1.37 Units on a scale | Standard Error 0.081 |
Secondary
Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle
Adverse Events (AE's) occurring after treatment that were thought to possibly indicate toxin spread throughout the trial conduct are defined as AE's of Special Interests. Values reported here refer to the number of participants affected.
Time frame: Up to End of study visit (Week 24-72)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | 2nd Injection Cycle | 2 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | 1st Injection Cycle | 4 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | Overall Period | 5 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | 2nd Injection Cycle | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | 1st Injection Cycle | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | Overall Period | 1 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | 1st Injection Cycle | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | Overall Period | 1 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle | 2nd Injection Cycle | 1 Participants |
Secondary
Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle
Treatment-emergent Serious Adverse Events (TESAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected.
Time frame: Up to End of study visit (Week 24-72)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | 2nd Injection Cycle | 3 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | 1st Injection Cycle | 4 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | Overall Period | 7 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | 2nd Injection Cycle | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | 1st Injection Cycle | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | Overall Period | 1 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | 1st Injection Cycle | 3 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | Overall Period | 6 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle | 2nd Injection Cycle | 3 Participants |
Secondary
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
Treatment-emergent Adverse Events (TEAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected.
Time frame: Up to End of study visit (Week 24-72)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovered/resolved w/ sequelae | 1 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: fatal | 0 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: unknown | 1 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovered/resolved | 42 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovering/resolving | 0 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovering/resolving | 2 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: unknown | 0 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: not recovered/ not resolved | 6 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovered/resolved | 52 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovered/resolved w/ sequela | 1 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: not recovered/ not resolved | 3 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovered/resolved w/ sequel | 0 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: not recovered/ not resolved | 3 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: fatal | 0 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: fatal | 0 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovered/resolved | 74 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovering/resolving | 2 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: unknown | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovering/resolving | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovered/resolved w/ sequelae | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: unknown | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: fatal | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: fatal | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovered/resolved | 15 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: not recovered/ not resolved | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: unknown | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: not recovered/ not resolved | 2 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovered/resolved w/ sequela | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovering/resolving | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovered/resolved | 14 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: fatal | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovered/resolved w/ sequel | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: unknown | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovering/resolving | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: not recovered/ not resolved | 2 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovered/resolved | 25 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: not recovered/ not resolved | 3 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovered/resolved | 17 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovering/resolving | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: not recovered/ not resolved | 1 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: recovered/resolved w/ sequela | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: fatal | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 1st Injection Cycle: unknown | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovering/resolving | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: not recovered/ not resolved | 2 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovered/resolved w/ sequel | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: fatal | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: unknown | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovered/resolved | 28 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovering/resolving | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: recovered/resolved w/ sequelae | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: fatal | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | Overall: unknown | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle | 2nd Injection Cycle: recovered/resolved | 20 Participants |
Secondary
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
Treatment-emergent Adverse Events (TEAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected.
Time frame: Up to End of study visit (Week 24-72)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Moderate AE's | 18 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Moderate AE's | 17 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Moderate AE's | 33 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Severe AE's | 2 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Mild AE's | 41 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Mild AE's | 35 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Mild AE's | 24 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Severe AE's | 1 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Severe AE's | 3 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Severe AE's | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Moderate AE's | 9 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Severe AE's | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Mild AE's | 9 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Moderate AE's | 5 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Mild AE's | 14 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Moderate AE's | 11 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Severe AE's | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Mild AE's | 6 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Moderate AE's | 9 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Moderate AE's | 4 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Moderate AE's | 10 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Mild AE's | 11 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Mild AE's | 14 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 2nd Injection Cycle: Severe AE's | 1 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Severe AE's | 1 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | 1st Injection Cycle: Severe AE's | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle | Overall: Mild AE's | 19 Participants |
Secondary
Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle
Treatment-emergent Adverse Events (TEASs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected.
Time frame: Up to End of study visit (Week 24-72)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | 2nd Injection Cycle | 0 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | 1st Injection Cycle | 1 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | Overall Period | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | 2nd Injection Cycle | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | 1st Injection Cycle | 0 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | Overall Period | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | 1st Injection Cycle | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | Overall Period | 0 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle | 2nd Injection Cycle | 0 Participants |
Secondary
Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle
Treatment-emergent Adverse Events (TEAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected.
Time frame: Up to End of study visit (Week 24-72)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | 2nd Injection Cycle | 4 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | 1st Injection Cycle | 7 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | Overall Period | 11 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | 2nd Injection Cycle | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | 1st Injection Cycle | 1 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | Overall Period | 2 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | 1st Injection Cycle | 2 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | Overall Period | 2 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle | 2nd Injection Cycle | 1 Participants |
Secondary
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
Treatment-emergent Adverse Events (TEAEs) are events observed from the time point of first injection until end of study visit (week 24-72). Values reported here refer to the number of participants affected.
Time frame: Up to End of study visit (Week 24-72)
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 2nd Injection Cycle | 44 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 1st Injection Cycle | 53 Participants |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall Period | 77 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 2nd Injection Cycle | 15 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 1st Injection Cycle | 15 Participants |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall Period | 26 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 1st Injection Cycle | 18 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall Period | 30 Participants |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 2nd Injection Cycle | 21 Participants |
Secondary
Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle
Time frame: Baseline up to Week 24-72
Population: FAS population is subset in the SES for whom the primary efficacy variable (participants who had at least an AS score of plantar flexor at baseline \[Day 1\] or the investigator's GICS-PF \[for participants with bilateral treatment on same body side\] at Day 29 \[Week 4\] of the first injection cycle) were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle | 1st Injection cycle | 15.3 Weeks | Standard Deviation 4.6 |
| High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle | 2nd Injection Cycle | 17 Weeks | Standard Deviation 6.5 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle | 1st Injection cycle | 15.9 Weeks | Standard Deviation 5.7 |
| Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle | 2nd Injection Cycle | 17.9 Weeks | Standard Deviation 7.8 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle | 1st Injection cycle | 15.7 Weeks | Standard Deviation 5.9 |
| Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin) | Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle | 2nd Injection Cycle | 15.5 Weeks | Standard Deviation 4.9 |