Trial Outcomes & Findings for Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Leg(s) in Cerebral Palsy (NCT NCT01893411)
NCT ID: NCT01893411
Last Updated: 2021-08-05
Results Overview
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.
COMPLETED
PHASE3
311 participants
Baseline, Week 4
2021-08-05
Participant Flow
The Safety Evaluation Set (SES) is the subset of all participants treated with study medication at least once.
Participant milestones
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
Participants received 16 Unit per kilogram (U/kg) Body Weight (BW) of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
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.
|
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
156
|
77
|
78
|
|
Overall Study
COMPLETED
|
139
|
70
|
69
|
|
Overall Study
NOT COMPLETED
|
17
|
7
|
9
|
Reasons for withdrawal
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
Participants received 16 Unit per kilogram (U/kg) Body Weight (BW) of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
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.
|
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.
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
|
Overall Study
Physician Decision
|
1
|
1
|
2
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
0
|
|
Overall Study
Other
|
3
|
1
|
3
|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
7
|
4
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
1
|
Baseline Characteristics
Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Leg(s) in Cerebral Palsy
Baseline characteristics by cohort
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
Total
n=311 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
156 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
311 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
6.4 years
STANDARD_DEVIATION 3.9 • n=5 Participants
|
6.6 years
STANDARD_DEVIATION 3.8 • n=7 Participants
|
7.1 years
STANDARD_DEVIATION 4.6 • n=5 Participants
|
6.6 years
STANDARD_DEVIATION 4.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
83 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
169 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
73 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
142 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 4Population: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
—
|
-0.66 Units on a scale
Standard Error 0.084
|
|
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
|
-0.66 Units on a scale
Standard Error 0.088
|
PRIMARY outcome
Timeframe: Baseline, Week 4Population: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
—
|
1.37 Units on a scale
Standard Error 0.081
|
|
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
|
1.32 Units on a scale
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Baseline, Week 4 of 1st IC and Week 16-40 of 2nd ICPopulation: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
—
|
-0.61 Units on a scale
Standard Error 0.104
|
|
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
|
-0.58 Units on a scale
Standard Error 0.108
|
|
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
|
—
|
-0.74 Units on a scale
Standard Error 0.106
|
|
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
|
-0.76 Units on a scale
Standard Error 0.123
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
—
|
-0.82 Units on a scale
Standard Error 0.082
|
|
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
|
-0.85 Units on a scale
Standard Error 0.091
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
-0.69 Units on a scale
Standard Error 0.086
|
|
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
|
—
|
-0.69 Units on a scale
Standard Error 0.08
|
|
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
|
—
|
-0.58 Units on a scale
Standard Error 0.077
|
|
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
|
-0.59 Units on a scale
Standard Error 0.085
|
|
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
|
—
|
-0.76 Units on a scale
Standard Error 0.079
|
|
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
|
-0.79 Units on a scale
Standard Error 0.09
|
|
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
|
—
|
-0.65 Units on a scale
Standard Error 0.079
|
|
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
|
-0.68 Units on a scale
Standard Error 0.085
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
—
|
-0.39 Units on a scale
Standard Error 0.214
|
|
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
|
-0.32 Units on a scale
Standard Error 0.204
|
|
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
|
—
|
-0.79 Units on a scale
Standard Error 0.2
|
|
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
|
-0.67 Units on a scale
Standard Error 0.19
|
|
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
|
—
|
-0.76 Units on a scale
Standard Error 0.506
|
|
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
Standard Error NA
NA = data not estimable due to low sample sizes
|
NA Units on a scale
Standard Error NA
NA = data not estimable due to low sample sizes
|
|
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
Standard Error NA
NA = data not estimable due to low sample sizes
|
—
|
NA Units on a scale
Standard Error NA
NA = data not estimable due to low sample sizes
|
|
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
Standard Error NA
NA = data not estimable due to low sample sizes
|
NA Units on a scale
Standard Error NA
NA = data not estimable due to low sample sizes
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
—
|
-2.56 Angle
Standard Error 1.231
|
|
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
|
-2.47 Angle
Standard Error 1.367
|
|
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
|
—
|
-2.63 Angle
Standard Error 1.267
|
|
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
|
-2.56 Angle
Standard Error 1.372
|
|
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
|
—
|
-2.67 Angle
Standard Error 1.157
|
|
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
|
-2.59 Angle
Standard Error 1.213
|
|
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
|
—
|
-3.83 Angle
Standard Error 1.594
|
|
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
|
-3.6 Angle
Standard Error 1.713
|
|
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
|
—
|
-4.25 Angle
Standard Error 1.44
|
|
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
|
-4.04 Angle
Standard Error 1.575
|
|
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
|
—
|
-5.68 Angle
Standard Error 1.298
|
|
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
|
-5.45 Angle
Standard Error 1.455
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
1.3 Units on a scale
Standard Error 0.216
|
|
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
|
—
|
1.35 Units on a scale
Standard Error 0.076
|
|
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
|
1.33 Units on a scale
Standard Error 0.086
|
|
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
|
—
|
1.64 Units on a scale
Standard Error 0.223
|
|
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
|
—
|
1.43 Units on a scale
Standard Error 0.092
|
|
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
|
1.39 Units on a scale
Standard Error 0.105
|
|
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
|
—
|
1.38 Units on a scale
Standard Error 0.096
|
|
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
|
1.46 Units on a scale
Standard Error 0.104
|
|
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
|
—
|
1.66 Units on a scale
Standard Error 0.224
|
|
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
|
1.53 Units on a scale
Standard Error 0.283
|
|
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
|
—
|
1.34 Units on a scale
Standard Error 0.101
|
|
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
|
1.4 Units on a scale
Standard Error 0.109
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
—
|
1.38 Units on a scale
Standard Error 0.098
|
|
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
|
—
|
1.37 Units on a scale
Standard Error 0.081
|
|
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
|
1.32 Units on a scale
Standard Error 0.09
|
|
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
|
1.48 Units on a scale
Standard Error 0.103
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
—
|
1.64 Units on a scale
Standard Error 0.392
|
|
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
|
1.49 Units on a scale
Standard Error 0.445
|
|
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
|
—
|
2.46 Units on a scale
Standard Error 0.488
|
|
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
|
2.59 Units on a scale
Standard Error 0.539
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
-1.47 Units on a scale
Standard Error 0.261
|
|
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
|
—
|
-1.16 Units on a scale
Standard Error 0.302
|
|
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
|
-0.44 Units on a scale
Standard Error 0.113
|
|
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
|
—
|
-1.32 Units on a scale
Standard Error 0.23
|
|
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
|
-1.61 Units on a scale
Standard Error 0.31
|
|
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
|
—
|
-0.93 Units on a scale
Standard Error 0.265
|
|
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
|
-1.06 Units on a scale
Standard Error 0.308
|
|
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
|
—
|
-1.13 Units on a scale
Standard Error 0.241
|
|
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
|
—
|
-0.49 Units on a scale
Standard Error 0.089
|
|
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
|
-0.34 Units on a scale
Standard Error 0.093
|
|
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
|
—
|
-0.47 Units on a scale
Standard Error 0.092
|
|
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
|
-0.33 Units on a scale
Standard Error 0.091
|
|
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
|
—
|
-0.37 Units on a scale
Standard Error 0.095
|
|
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
|
-0.3 Units on a scale
Standard Error 0.095
|
|
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
|
—
|
-1.03 Units on a scale
Standard Error 0.289
|
|
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
|
-1.53 Units on a scale
Standard Error 0.351
|
|
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
|
-1.61 Units on a scale
Standard Error 0.315
|
|
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
|
—
|
-0.97 Units on a scale
Standard Error 0.333
|
|
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
|
-1.4 Units on a scale
Standard Error 0.336
|
|
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
|
—
|
-0.47 Units on a scale
Standard Error 0.102
|
|
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
|
-0.46 Units on a scale
Standard Error 0.105
|
|
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
|
—
|
-0.47 Units on a scale
Standard Error 0.104
|
|
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
|
—
|
-0.4 Units on a scale
Standard Error 0.112
|
|
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
|
-0.33 Units on a scale
Standard Error 0.121
|
SECONDARY outcome
Timeframe: Baseline up to Week 24-72Population: 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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
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
|
17.9 Weeks
Standard Deviation 7.8
|
15.5 Weeks
Standard Deviation 4.9
|
|
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
|
15.9 Weeks
Standard Deviation 5.7
|
15.7 Weeks
Standard Deviation 5.9
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
1st Injection Cycle
|
53 Participants
|
15 Participants
|
18 Participants
|
|
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
2nd Injection Cycle
|
44 Participants
|
15 Participants
|
21 Participants
|
|
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
Overall Period
|
77 Participants
|
26 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle
1st Injection Cycle
|
4 Participants
|
1 Participants
|
0 Participants
|
|
Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle
2nd Injection Cycle
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle
Overall Period
|
5 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle
1st Injection Cycle
|
4 Participants
|
0 Participants
|
3 Participants
|
|
Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle
2nd Injection Cycle
|
3 Participants
|
1 Participants
|
3 Participants
|
|
Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle
Overall Period
|
7 Participants
|
1 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle
1st Injection Cycle
|
7 Participants
|
1 Participants
|
2 Participants
|
|
Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle
2nd Injection Cycle
|
4 Participants
|
1 Participants
|
1 Participants
|
|
Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle
Overall Period
|
11 Participants
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
1st Injection Cycle: Severe AE's
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
2nd Injection Cycle: Mild AE's
|
24 Participants
|
9 Participants
|
11 Participants
|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
2nd Injection Cycle: Moderate AE's
|
18 Participants
|
5 Participants
|
9 Participants
|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
2nd Injection Cycle: Severe AE's
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
1st Injection Cycle: Mild AE's
|
35 Participants
|
6 Participants
|
14 Participants
|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
1st Injection Cycle: Moderate AE's
|
17 Participants
|
9 Participants
|
4 Participants
|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
Overall: Mild AE's
|
41 Participants
|
14 Participants
|
19 Participants
|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
Overall: Moderate AE's
|
33 Participants
|
11 Participants
|
10 Participants
|
|
Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
Overall: Severe AE's
|
3 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
1st Injection Cycle: recovered/resolved
|
52 Participants
|
15 Participants
|
17 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
1st Injection Cycle: recovering/resolving
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
2nd Injection Cycle: recovered/resolved
|
42 Participants
|
14 Participants
|
20 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
2nd Injection Cycle: recovering/resolving
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
2nd Injection Cycle: not recovered/ not resolved
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
2nd Injection Cycle: unknown
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
Overall: recovered/resolved
|
74 Participants
|
25 Participants
|
28 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
Overall: recovering/resolving
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
Overall: not recovered/ not resolved
|
6 Participants
|
2 Participants
|
3 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
Overall: recovered/resolved w/ sequelae
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
Overall: unknown
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
1st Injection Cycle: not recovered/ not resolved
|
3 Participants
|
0 Participants
|
1 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
1st Injection Cycle: recovered/resolved w/ sequela
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
1st Injection Cycle: fatal
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
1st Injection Cycle: unknown
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
2nd Injection Cycle: recovered/resolved w/ sequel
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
2nd Injection Cycle: fatal
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
Overall: fatal
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 Participants
Participants received 16 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 400 Units per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 Participants
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 Units per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 Participants
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 Units per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle
1st Injection Cycle
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle
2nd Injection Cycle
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle
Overall Period
|
1 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
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)
Serious adverse events
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 participants at risk
Participants received 16 Unit per kilogram (U/kg) Body Weight (BW) of IncobotulinumtoxinA (Xeomin) with a maximum of 400 U per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 participants at risk
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 U per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 participants at risk
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 U per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Brain contusion
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Injury, poisoning and procedural complications
Concussion
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Injury, poisoning and procedural complications
Craniocerebral injury
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Surgical and medical procedures
Strabismus correction
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Nervous system disorders
Epilepsy
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Nervous system disorders
Febrile convulsion
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Nervous system disorders
Partial seizures
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Gastrointestinal disorders
Nausea
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Gastrointestinal disorders
Vomiting
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Musculoskeletal and connective tissue disorders
Arthritis reactive
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Musculoskeletal and connective tissue disorders
Synovitis
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Infections and infestations
Pneumonia
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Infections and infestations
Borrelia infection
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Infections and infestations
Bronchitis
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Infections and infestations
Gastroenteritis
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Infections and infestations
Gastrointestinal infection
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Infections and infestations
Respiratory tract infection
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Infections and infestations
Tonsillitis
|
0.64%
1/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
0.00%
0/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
Other adverse events
| Measure |
High Dose: 16 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=156 participants at risk
Participants received 16 Unit per kilogram (U/kg) Body Weight (BW) of IncobotulinumtoxinA (Xeomin) with a maximum of 400 U per injection treatment via intramuscular injection into spastic muscles.
|
Mid Dose: 12 U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=77 participants at risk
Participants received 12 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 300 U per injection treatment via intramuscular injection into spastic muscles.
|
Low Dose: 4U/kg Body Weight Incobotulinumtoxin A (Xeomin)
n=78 participants at risk
Participants received 4 U/kg BW of IncobotulinumtoxinA (Xeomin) with a maximum of 100 U per injection treatment via intramuscular injection into spastic muscles.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.9%
3/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
5.1%
4/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
10.9%
17/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
10.4%
8/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
11.5%
9/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
1.9%
3/156 • From the timepoint of first injection until end of study visit (week 24-72)
|
1.3%
1/77 • From the timepoint of first injection until end of study visit (week 24-72)
|
9.0%
7/78 • From the timepoint of first injection until end of study visit (week 24-72)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
- Publication restrictions are in place
Restriction type: OTHER