PUL: Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02106351
• Collaborator: (none)
• Enrollment: 212
• Locations: 31
• Arms: 3
• Actual Duration (Months): 53.1
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of multiple doses of Dysport used in the treatment of upper limb spasticity (altered skeletal muscle performance) in children with cerebral palsy (CP).

Condition or Disease	Intervention/Treatment	Phase
Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children	Biological: Botulinum toxin type A	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 212 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicentre, Double Blind, Prospective, Randomised, Controlled, Multiple Treatment Study Assessing Efficacy And Safety Of DYSPORT® Used In The Treatment Of Upper Limb Spasticity In Children
• Actual Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Sep 21, 2017
• Actual Study Completion Date: Sep 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Group A - Treatments 1, 2, 3 and 4: Dysport 16 Units (U)/kg in one upper extremity (the study limb).	Biological: Botulinum toxin type A; Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.; Other Names: AbobotulinumtoxinA (Dysport®)
Experimental: Group B Group B - Treatments 1, 2, 3 and 4: Dysport 8 U/kg in one upper extremity (the study limb).	Biological: Botulinum toxin type A; Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.; Other Names: AbobotulinumtoxinA (Dysport®)
Experimental: Group C Group C - Treatment 1: Dysport 2 U/kg in one upper extremity (the study limb). Group C - Treatments 2, 3 and 4: Dysport 8 or 16 U/kg in one upper extremity (the study limb).	Biological: Botulinum toxin type A; Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.; Other Names: AbobotulinumtoxinA (Dysport®)

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG [Baseline (TC 1, Day 1) and TC 1, Week 6.]

   The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone.

Secondary Outcome Measures

1. Mean Physician's Global Assessment (PGA) Score at TC 1, Week 6 [TC 1, Week 6.]

   The PGA of treatment response was assessed by asking the investigator the following question: 'How would you rate the response to treatment in the subject's upper limb since the start of the study?'. Answers were on a 9-point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). The mean scores for each treatment group at TC 1, Week 6 are presented.

2. Mean Goal Attainment Scale (GAS) Total Score at TC 1, Week 6 [TC 1, Week 6.]

   The GAS is a functional 5-point scale used to measure progress towards individual therapy goals. At start of each TC, 1 to 3 individual goals were defined for each subject by investigator and child's parents/guardians/caregivers prior to treatment. Outcome to reach each goal was rated on a 5-point scale ranging from -2 to +2 (-2: much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, +1: somewhat more than expected outcome, +2: much more than expected outcome). Higher score indicates a better outcome. A GAS T-score was calculated as: 50+(10∑_(i=1)^n wi xi)/√(0.7∑_(i=1)^n wi^2 +0.3(∑_(i=1)^n wi)^2) where, xi = rating of ith goal post-baseline; wi = weight of ith goal, calculated as importance * difficulty as defined at baseline; n = number of goals assessed at baseline and post-baseline. A GAS T-score of 50 indicates goals achieved as expected. Scores below 50 reflect under attainment of goals and scores above 50 reflect over attainment of goals.

Other Outcome Measures

1. Mean Change From Baseline to TC 1 Week 16 in MAS Score in the TC 1 PTMG [Baseline (TC 1, Day 1) and TC 1, Week 16.]

   The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone.

2. Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Elbow Flexors of the Study Limb [Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.]

   The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the elbow flexors.

3. Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Wrist Flexors of the Study Limb [Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.]

   The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the wrist flexors.

4. Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Finger Flexors of the Study Limb [Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.]

   The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the finger flexors.

5. Mean PGA Score at TC 1 Week 16 [Baseline (TC 1, Day 1) and TC 1, Week 16.]

   The PGA of treatment response was assessed by asking the investigator the following question: 'How would you rate the response to treatment in the subject's upper limb since the start of the study?'. Answers were on a 9-point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). The mean scores for each treatment group at TC 1 Week 16 are presented.

6. Mean GAS Total Score at TC 1, Week 16 [Baseline (TC 1, Day 1) and TC 1, Week 16.]

   The GAS is a functional 5-point scale used to measure progress towards individual therapy goals. At start of each TC, 1 to 3 individual goals were defined for each subject by investigator and child's parents/guardians/caregivers prior to treatment. Outcome to reach each goal was rated on a 5-point scale ranging from -2 to +2 (-2: much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, +1: somewhat more than expected outcome, +2: much more than expected outcome). Higher score indicates a better outcome. A GAS T-score was calculated as: 50+(10∑_(i=1)^n wi xi)/√(0.7∑_(i=1)^n wi^2 +0.3(∑_(i=1)^n wi)^2) where, xi = rating of ith goal post-baseline; wi = weight of ith goal, calculated as importance * difficulty as defined at baseline; n = number of goals assessed at baseline and post-baseline. A GAS T-score of 50 indicates goals achieved as expected. Scores below 50 reflect under attainment of goals and scores above 50 reflect over attainment of goals.

7. Mean Change From Baseline to TC 1, Week 16 in the Paediatric Quality of Life (PedsQL) Scores [Baseline (TC 1, Day 1) and TC 1, Week 16.]

   Parents/guardians completed questionnaires on their child's quality of life. The PedsQL parent inventory measured healthcare concepts for children/adolescents aged 2-18 years. The Generic Core Scales include physical, emotional, social and school aspects. The CP module was also completed. Scores were transformed on a scale from 0 to 100 with higher scores indicating a better quality of life. Mean changes from baseline to TC 1, Week 16 are presented for the General Core Scale and for the CP module. A positive change from baseline indicates an improvement in quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Upper limb spasticity due to cerebral palsy

• Body weight 10 kg or over

• MAS score of 2 or more in affected elbow or wrist flexors

Exclusion Criteria:

• Fixed myocontracture

• Previous phenol or alcohol injection within 1 year

• Severe athetoid or dystonic movements

• Previous or planned surgery for spasticity in elbow or wrist flexors

• Neuromuscular disorders

• Previous Rhizotomy within 6 months

• Intrathecal baclofen within 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Aurora	Colorado	United States
2		Washington	District of Columbia	United States
3		New Orleans	Louisiana	United States
4		Royal Oak	Michigan	United States
5		Saint Paul	Minnesota	United States
6		Omaha	Nebraska	United States
7		Albuquerque	New Mexico	United States
8		New York	New York	United States
9		Columbus	Ohio	United States
10		Portland	Oregon	United States
11		Austin	Texas	United States
12		Dallas	Texas	United States
13		Brussels		Belgium
14		Brno		Czechia
15		Prague		Czechia
16		Be'er Sheva		Israel
17		Jerusalem		Israel
18		Petaẖ Tiqwa		Israel
19		Tel Aviv		Israel
20		Tel Hashomer		Israel
21		La Paz	Baja California Sur	Mexico
22		Celaya		Mexico
23		Monterrey		Mexico
24		Gdansk		Poland
25		Poznan		Poland
26		Wiazowna		Poland
27		Barcelona		Spain
28		Terrassa		Spain
29		Istanbul		Turkey
30		Izmir		Turkey
31		Kocaeli		Turkey

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

• Study Protocol - Jul 24, 2017
• Statistical Analysis Plan - Oct 19, 2018

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT02106351
• Other Study ID Numbers: Y-52-52120-153; 2010-021817-22
• First Posted: Apr 8, 2014
• Last Update Posted: Dec 24, 2019
• Last Verified: Dec 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Muscle Spasticity; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Recruitment Details	Male and female subjects aged between 2 and 17 years with upper limb spasticity due to cerebral palsy (CP) were recruited from April 2014 and the study completed in September 2018. Subjects could receive a maximum of 4 treatment cycles (TC) over a minimum of 1 year and maximum of 1 year and 9 months, with at least 16 weeks between each TC.
Pre-assignment Detail	Subjects had a body weight ≥10 kilograms (kg), increased muscle tone/spasticity in at least 1 upper limb, a modified Ashworth scale (MAS) score ≥2 in the upper limb primary targeted muscle group (PTMG) of the study limb at baseline. Subjects were stratified according to age (2-9 and 10-17 years) and Botulinum Toxin (BTX) naïve or non-naïve status.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 Units per kg (U/kg) by intramuscular (IM) injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4). Retreatment was based on clinical need with a minimum retreatment interval of 16 weeks. In all TCs the dose was divided between the PTMG (elbow or wrist flexors) and a number of other upper limb muscles based on clinical presentation. From TC 2 onwards dose adaptation was permitted as well as treatment of the non-study upper limb and lower limbs.	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U. Retreatment was based on clinical need with a minimum retreatment interval of 16 weeks. In all TCs the dose was divided between the PTMG (elbow or wrist flexors) and a number of other upper limb muscles based on clinical presentation. From TC 2 onwards dose adaptation was permitted as well as treatment of the non-study upper limb and lower limbs.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U. Retreatment was based on clinical need with a minimum retreatment interval of 16 weeks. In all TCs the dose was divided between the PTMG (elbow or wrist flexors) and a number of other upper limb muscles based on clinical presentation. From TC 2 onwards dose adaptation was permitted as well as treatment of the non-study upper limb and lower limbs.
Period Title: Treatment Cycle 1
STARTED	71	70	71
Received Treatment in TC 1	70	70	70
COMPLETED	66	67	67
NOT COMPLETED	5	3	4
Period Title: Treatment Cycle 1
STARTED	0	88	90
COMPLETED	0	83	87
NOT COMPLETED	0	5	3
Period Title: Treatment Cycle 1
STARTED	0	49	58
COMPLETED	0	45	53
NOT COMPLETED	0	4	5
Period Title: Treatment Cycle 1
STARTED	0	22	33
COMPLETED	0	21	31
NOT COMPLETED	0	1	2

Baseline Characteristics

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg	Total
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.	Total of all reporting groups
Overall Participants	70	70	70	210
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.91 (4.55)	8.97 (4.27)	9.17 (4.30)	9.02 (4.36)
Age, Customized (Count of Participants)
2 - 9 Years	40 57.1%	40 57.1%	40 57.1%	120 57.1%
10 - 17 Years	30 42.9%	30 42.9%	30 42.9%	90 42.9%
Sex: Female, Male (Count of Participants)
Female	32 45.7%	24 34.3%	28 40%	84 40%
Male	38 54.3%	46 65.7%	42 60%	126 60%
Race/Ethnicity, Customized (Count of Participants)
Asian	2 2.9%	1 1.4%	0 0%	3 1.4%
Black or African American	7 10%	6 8.6%	3 4.3%	16 7.6%
White	49 70%	54 77.1%	54 77.1%	157 74.8%
American Indian or Alaska Native	0 0%	1 1.4%	0 0%	1 0.5%
Multiple	12 17.1%	8 11.4%	13 18.6%	33 15.7%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	16 22.9%	13 18.6%	15 21.4%	44 21%
Not Hispanic or Latino	54 77.1%	57 81.4%	55 78.6%	166 79%
BTX Status (Count of Participants)
BTX naïve	25 35.7%	23 32.9%	24 34.3%	72 34.3%
BTX non-naïve	45 64.3%	47 67.1%	46 65.7%	138 65.7%
Baseline MAS Score in the PTMG (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	3.1 (0.3)	3.1 (0.3)	3.1 (0.5)	3.1 (0.4)

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG
Description	The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone.
Time Frame	Baseline (TC 1, Day 1) and TC 1, Week 6.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	69	69	70
Mean (Standard Deviation) [score on a scale]	-1.5 (1.1)	-1.9 (1.0)	-2.2 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dysport 2 U/kg, Dysport 8 U/kg
	Comments	The treatment difference between Dysport 8 U/kg and Dysport 2 U/kg was analysed using an analysis of covariance (ANCOVA) on the ranked changes from baseline. The model included treatment group, the baseline value, the 2 stratification factors (age range and BTX status at baseline) and the pooled centre as fixed effects. The derived least squares (LS) means were back transformed to the original scale and the treatment difference determined.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0118
	Comments	The 2-tailed significance level was 0.05.
	Method	ANCOVA
	Comments	ANCOVA is performed on the ranked values.
Method of Estimation	Estimation Parameter	LS mean difference back transformed
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dysport 2 U/kg, Dysport 16 U/kg
	Comments	The treatment difference between Dysport 16 U/kg and Dysport 2 U/kg was analysed using an ANCOVA on the ranked changes from baseline. The model included treatment group, the baseline value, the 2 stratification factors (age range and BTX status at baseline) and the pooled centre as fixed effects. The derived LS means were back transformed to the original scale and the treatment difference determined.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The 2-tailed significance level was 0.05.
	Method	ANCOVA
	Comments	ANCOVA is performed on the ranked values.
Method of Estimation	Estimation Parameter	LS mean difference back transformed
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Physician's Global Assessment (PGA) Score at TC 1, Week 6
Description	The PGA of treatment response was assessed by asking the investigator the following question: 'How would you rate the response to treatment in the subject's upper limb since the start of the study?'. Answers were on a 9-point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). The mean scores for each treatment group at TC 1, Week 6 are presented.
Time Frame	TC 1, Week 6.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects with data available are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	68	69	70
Mean (Standard Deviation) [score on a scale]	1.7 (0.9)	2.0 (0.9)	2.0 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dysport 2 U/kg, Dysport 8 U/kg
	Comments	The treatment difference between Dysport 8 U/kg and Dysport 2 U/kg was analysed using an analysis of variance (ANOVA) on the rank of the PGA score at TC 1, Week 6. The model included treatment group, the 2 stratification factors (age range and BTX status at baseline) and the centre as fixed effects. The derived LS means were back transformed to the original scale and the treatment difference determined.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2043
	Comments	The two-tailed significance level was 0.05.
	Method	ANOVA
	Comments	ANOVA was performed on ranked values.
Method of Estimation	Estimation Parameter	LS mean difference back transformed
	Estimated Value	0.2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dysport 2 U/kg, Dysport 16 U/kg
	Comments	The treatment difference between Dysport 16 U/kg and Dysport 2 U/kg was analysed using an ANOVA on the rank of the PGA score at TC 1, Week 6. The model included treatment group, the 2 stratification factors (age range and BTX status at baseline) and the centre as fixed effects. The derived LS means were back transformed to the original scale and the treatment difference determined.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1880
	Comments	The two-tailed significance level was 0.05.
	Method	ANOVA
	Comments	ANOVA was performed on ranked values.
Method of Estimation	Estimation Parameter	LS mean difference back transformed
	Estimated Value	0.2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Goal Attainment Scale (GAS) Total Score at TC 1, Week 6
Description	The GAS is a functional 5-point scale used to measure progress towards individual therapy goals. At start of each TC, 1 to 3 individual goals were defined for each subject by investigator and child's parents/guardians/caregivers prior to treatment. Outcome to reach each goal was rated on a 5-point scale ranging from -2 to +2 (-2: much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, +1: somewhat more than expected outcome, +2: much more than expected outcome). Higher score indicates a better outcome. A GAS T-score was calculated as: 50+(10∑_(i=1)^n wi xi)/√(0.7∑_(i=1)^n wi^2 +0.3(∑_(i=1)^n wi)^2) where, xi = rating of ith goal post-baseline; wi = weight of ith goal, calculated as importance * difficulty as defined at baseline; n = number of goals assessed at baseline and post-baseline. A GAS T-score of 50 indicates goals achieved as expected. Scores below 50 reflect under attainment of goals and scores above 50 reflect over attainment of goals.
Time Frame	TC 1, Week 6.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects with data available are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	68	66	70
Mean (Standard Deviation) [T-score]	51.3 (9.9)	52.6 (10.1)	52.0 (9.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dysport 2 U/kg, Dysport 8 U/kg
	Comments	The treatment difference between Dysport 8 U/kg and Dysport 2 U/kg was analysed using ANOVA on the GAS Total score at TC 1, Week 6. The model included treatment group, the 2 stratification factors (age range and BTX status at baseline) and the centre as fixed effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7648
	Comments	The two-tailed significance level was 0.05.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -2.7 to 3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dysport 2 U/kg, Dysport 16 U/kg
	Comments	The treatment difference between Dysport 16 U/kg and Dysport 2 U/kg was analysed using ANOVA on the GAS Total score at TC 1, Week 6. The model included treatment group, the 2 stratification factors (age range and BTX status at baseline) and the centre as fixed effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7429
	Comments	The two-tailed significance level was 0.05.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -2.6 to 3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Other Pre-specified Outcome

Title	Mean Change From Baseline to TC 1 Week 16 in MAS Score in the TC 1 PTMG
Description	The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone.
Time Frame	Baseline (TC 1, Day 1) and TC 1, Week 16.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects with data available at the timepoint analysed are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	68	68	68
Mean (Standard Deviation) [score on a scale]	-1.0 (1.0)	-1.4 (1.1)	-1.6 (1.2)

5. Other Pre-specified Outcome

Title	Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Elbow Flexors of the Study Limb
Description	The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the elbow flexors.
Time Frame	Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects with data available at each timepoint and who were injected in the elbow flexors are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	69	69	70
Week 6	-1.0 (1.1)	-1.7 (1.1)	-1.9 (1.2)
Week 16	-0.6 (1.0)	-1.2 (1.2)	-1.3 (1.4)

6. Other Pre-specified Outcome

Title	Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Wrist Flexors of the Study Limb
Description	The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the wrist flexors.
Time Frame	Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects with data available at each timepoint and who were injected in the wrist flexors are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	69	69	70
Week 6	-1.3 (1.1)	-1.5 (1.2)	-1.7 (1.3)
Week 16	-0.9 (1.2)	-1.0 (1.2)	-1.3 (1.2)

7. Other Pre-specified Outcome

Title	Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Finger Flexors of the Study Limb
Description	The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the finger flexors.
Time Frame	Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects with data available at each timepoint and who were injected in the finger flexors are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	69	69	70
Week 6	-0.8 (0.9)	-1.8 (1.1)	-1.9 (1.0)
Week 16	-0.8 (1.3)	-1.3 (0.8)	-1.8 (1.0)

8. Other Pre-specified Outcome

Title	Mean PGA Score at TC 1 Week 16
Description	The PGA of treatment response was assessed by asking the investigator the following question: 'How would you rate the response to treatment in the subject's upper limb since the start of the study?'. Answers were on a 9-point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). The mean scores for each treatment group at TC 1 Week 16 are presented.
Time Frame	Baseline (TC 1, Day 1) and TC 1, Week 16.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects with available data at the timepoint analysed are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	69	69	70
Mean (Standard Deviation) [score on a scale]	1.7 (1.0)	1.6 (1.1)	1.9 (1.2)

9. Other Pre-specified Outcome

Title	Mean GAS Total Score at TC 1, Week 16
Description	The GAS is a functional 5-point scale used to measure progress towards individual therapy goals. At start of each TC, 1 to 3 individual goals were defined for each subject by investigator and child's parents/guardians/caregivers prior to treatment. Outcome to reach each goal was rated on a 5-point scale ranging from -2 to +2 (-2: much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, +1: somewhat more than expected outcome, +2: much more than expected outcome). Higher score indicates a better outcome. A GAS T-score was calculated as: 50+(10∑_(i=1)^n wi xi)/√(0.7∑_(i=1)^n wi^2 +0.3(∑_(i=1)^n wi)^2) where, xi = rating of ith goal post-baseline; wi = weight of ith goal, calculated as importance * difficulty as defined at baseline; n = number of goals assessed at baseline and post-baseline. A GAS T-score of 50 indicates goals achieved as expected. Scores below 50 reflect under attainment of goals and scores above 50 reflect over attainment of goals.
Time Frame	Baseline (TC 1, Day 1) and TC 1, Week 16.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects with available data at the timepoint analysed are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	69	69	70
Mean (Standard Deviation) [T-score]	54.7 (9.8)	54.2 (9.7)	55.1 (10.1)

10. Other Pre-specified Outcome

Title	Mean Change From Baseline to TC 1, Week 16 in the Paediatric Quality of Life (PedsQL) Scores
Description	Parents/guardians completed questionnaires on their child's quality of life. The PedsQL parent inventory measured healthcare concepts for children/adolescents aged 2-18 years. The Generic Core Scales include physical, emotional, social and school aspects. The CP module was also completed. Scores were transformed on a scale from 0 to 100 with higher scores indicating a better quality of life. Mean changes from baseline to TC 1, Week 16 are presented for the General Core Scale and for the CP module. A positive change from baseline indicates an improvement in quality of life.
Time Frame	Baseline (TC 1, Day 1) and TC 1, Week 16.

Outcome Measure Data

Analysis Population Description

The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6. Subjects who were assessed at each timepoint are presented.

Arm/Group Title	Dysport 2 U/kg	Dysport 8 U/kg	Dysport 16 U/kg
Arm/Group Description	Subjects were randomised to receive Dysport 2 U/kg by IM injection into the study upper limb in TC 1 and Dysport 8 U/kg or 16 U/kg in subsequent TCs (2, 3 and 4).	Subjects were randomised to receive Dysport 8 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 320 U.	Subjects were randomised to receive Dysport 16 U/kg by IM injection into the study upper limb in TC 1 and all subsequent TCs (2, 3 and 4), up to a maximum of 640 U.
Measure Participants	69	69	70
Generic Core Scale	3.4 (9.7)	3.4 (17.1)	2.0 (12.0)
CP Module	4.8 (16.8)	2.1 (14.9)	2.8 (16.2)

Adverse Events

Time Frame	Treatment emergent adverse events (TEAEs) were collected from the first injection of study treatment up to the end of TC 4 (up to 21 months).
Adverse Event Reporting Description	TEAEs are reported for the dose received prior to onset of the AE. Due to dose adaption due to safety lower doses were permitted for TCs 2 - 4.
Arm/Group Title	TC1: Dysport 2 U/kg		TC 1: Dysport 8 U/kg		TC 1: Dysport 16 U/kg		TC 2: Dysport 8 U/kg		TC 2: Dysport 16 U/kg		TC 3: Dysport 8 U/kg		TC 3: Dysport 16 U/kg		TC 4: Dysport 8 U/kg		TC 4: Dysport 16 U/kg
Arm/Group Description	Subjects randomised to Dysport 2 U/kg in TC 1.		Subjects randomised to Dysport 8 U/kg in TC 1.		Subjects randomised to Dysport 16 U/kg in TC 1.		Subjects who received Dysport 8 U/kg in TC 2.		Subjects who received Dysport 16 U/kg in TC 2.		Subjects who received Dysport 8 U/kg in TC 3.		Subjects who received Dysport 16 U/kg in TC 3.		Subjects who received Dysport 8 U/kg in TC 4.		Subjects who received Dysport 16 U/kg in TC 4.
All Cause Mortality
	TC1: Dysport 2 U/kg		TC 1: Dysport 8 U/kg		TC 1: Dysport 16 U/kg		TC 2: Dysport 8 U/kg		TC 2: Dysport 16 U/kg		TC 3: Dysport 8 U/kg		TC 3: Dysport 16 U/kg		TC 4: Dysport 8 U/kg		TC 4: Dysport 16 U/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		0/70 (0%)		0/70 (0%)		0/88 (0%)		0/90 (0%)		0/49 (0%)		0/58 (0%)		0/22 (0%)		0/33 (0%)
Serious Adverse Events
	TC1: Dysport 2 U/kg		TC 1: Dysport 8 U/kg		TC 1: Dysport 16 U/kg		TC 2: Dysport 8 U/kg		TC 2: Dysport 16 U/kg		TC 3: Dysport 8 U/kg		TC 3: Dysport 16 U/kg		TC 4: Dysport 8 U/kg		TC 4: Dysport 16 U/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/70 (5.7%)		2/70 (2.9%)		2/70 (2.9%)		6/88 (6.8%)		1/90 (1.1%)		3/49 (6.1%)		2/58 (3.4%)		2/22 (9.1%)		1/33 (3%)
Gastrointestinal disorders
Gastritis	1/70 (1.4%)	1	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Vomiting	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	1/58 (1.7%)	1	1/22 (4.5%)	1	0/33 (0%)	0
Abdominal pain	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
General disorders
Pyrexia	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/88 (1.1%)	1	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Infections and infestations
Appendicitis	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/88 (1.1%)	1	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Escherichia urinary tract infection	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/88 (1.1%)	1	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Gastroenteritis	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/88 (1.1%)	1	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Influenza	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/88 (1.1%)	1	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Gastroenteritis viral	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	1/49 (2%)	1	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Injury, poisoning and procedural complications
Fall	1/70 (1.4%)	1	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Humerus fracture	1/70 (1.4%)	1	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Hand fracture	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	1/33 (3%)	1
Investigations
C-reactive protein increased	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/88 (1.1%)	1	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Electrocardiogram ST segment elevation	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Testicular malignant teratoma	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	1/90 (1.1%)	1	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Nervous system disorders
Epilepsy	0/70 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	2/58 (3.4%)	2	0/22 (0%)	2	0/33 (0%)	2
Focal dyscognitive seizures	0/70 (0%)	0	0/70 (0%)	0	1/70 (1.4%)	1	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Cerebral ventricle dilatation	0/70 (0%)	0	1/70 (1.4%)	1	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Seizure	1/70 (1.4%)	1	0/70 (0%)	0	0/70 (0%)	0	2/88 (2.3%)	2	0/90 (0%)	0	1/49 (2%)	2	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Cerebrovascular accident	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Headache	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Psychiatric disorders
Depression	0/70 (0%)	0	1/70 (1.4%)	1	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/88 (1.1%)	1	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Surgical and medical procedures
Medical device removal	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	1/49 (2%)	1	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Muscle release	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	1/49 (2%)	1	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Ostectomy	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	1/49 (2%)	1	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Radiotherapy to bone	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	1/49 (2%)	1	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Scoliosis surgery	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Other (Not Including Serious) Adverse Events
	TC1: Dysport 2 U/kg		TC 1: Dysport 8 U/kg		TC 1: Dysport 16 U/kg		TC 2: Dysport 8 U/kg		TC 2: Dysport 16 U/kg		TC 3: Dysport 8 U/kg		TC 3: Dysport 16 U/kg		TC 4: Dysport 8 U/kg		TC 4: Dysport 16 U/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/70 (21.4%)		23/70 (32.9%)		19/70 (27.1%)		18/88 (20.5%)		17/90 (18.9%)		14/49 (28.6%)		10/58 (17.2%)		14/22 (63.6%)		5/33 (15.2%)
Cardiac disorders
Tachycardia	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Eye disorders
Eye pruritus	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Gastrointestinal disorders
Vomiting	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	3/49 (6.1%)	3	2/58 (3.4%)	3	0/22 (0%)	0	0/33 (0%)	0
Nausea	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Dental caries	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
General disorders
Pyrexia	2/70 (2.9%)	2	4/70 (5.7%)	5	2/70 (2.9%)	2	7/88 (8%)	8	1/90 (1.1%)	1	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Injection site bruising	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Injection site rash	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Immune system disorders
Seasonal allergy	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Infections and infestations
Viral upper respiratory tract infection	10/70 (14.3%)	13	6/70 (8.6%)	7	6/70 (8.6%)	7	7/88 (8%)	8	6/90 (6.7%)	6	6/49 (12.2%)	9	5/58 (8.6%)	8	0/22 (0%)	0	3/33 (9.1%)	3
Upper respiratory tract infection	5/70 (7.1%)	6	6/70 (8.6%)	8	8/70 (11.4%)	10	5/88 (5.7%)	5	4/90 (4.4%)	4	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Pharyngitis	6/70 (8.6%)	8	3/70 (4.3%)	3	4/70 (5.7%)	4	0/88 (0%)	0	0/90 (0%)	0	4/49 (8.2%)	4	2/58 (3.4%)	2	0/22 (0%)	0	0/33 (0%)	0
Sinusitis	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	1/49 (2%)	1	3/58 (5.2%)	3	1/22 (4.5%)	1	2/33 (6.1%)	2
Ear infection	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	1/33 (3%)	1
Gastroenteritis	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	1/33 (3%)	1
Urinary tract infection	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	1/33 (3%)	1
Impetigo	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Laryngitis	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Pharyngitis streptococcal	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Pneumonia	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Viral infection	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Conjunctivitis	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Injury, poisoning and procedural complications
Skin abrasion	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	1/88 (1.1%)	1	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Anaemia postoperative	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Postoperative ileus	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Procedural pain	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Contusion	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Fall	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Investigations
Intenational normalised ratio increased	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Metabolism and nutrition disorders
Hyponatraemia	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	1/70 (1.4%)	1	3/70 (4.3%)	3	4/70 (5.7%)	4	0/88 (0%)	0	5/90 (5.6%)	5	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Pain in extremity	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Nervous system disorders
Headache	0/70 (0%)	0	4/70 (5.7%)	6	2/70 (2.9%)	2	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	0/22 (0%)	0	0/33 (0%)	0
Epilepsy	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	3	0/33 (0%)	0
Psychiatric disorders
Insomnia	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	0/70 (0%)	0	5/70 (7.1%)	6	1/70 (1.4%)	1	1/88 (1.1%)	1	1/90 (1.1%)	1	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Pleural effusion	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0
Skin and subcutaneous tissue disorders
Rash erythematous	0/70 (0%)	0	0/70 (0%)	0	0/70 (0%)	0	0/88 (0%)	0	0/90 (0%)	0	0/49 (0%)	0	0/58 (0%)	0	1/22 (4.5%)	1	0/33 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.