Efficacy And Safety Of Dysport In The Treatment Of Upper... | NCT02106351 | Trialant
NCT02106351
Sponsor
Ipsen
Status
Completed
Last Update Posted
Sep 28, 2022Actual
Enrollment
212Actual
Phase
Phase 3
Conditions
Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children
Interventions
Botulinum toxin type A
Countries
United States
Belgium
Czechia
Israel
Mexico
Poland
Spain
Turkey (Türkiye)
Protocol Section
Identification Module
NCT ID
NCT02106351
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
Y-52-52120-153
Secondary IDs
ID
Type
Description
Link
2010-021817-22
EudraCT Number
Brief Title
Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children
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
Acronym
PUL
Organization
IpsenINDUSTRY
Status Module
Record Verification Date
Sep 2022
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Apr 2014Actual
Primary Completion Date
Sep 21, 2017Actual
Completion Date
Sep 4, 2018Actual
First Submitted Date
Apr 3, 2014
First Submission Date that Met QC Criteria
Apr 7, 2014
First Posted Date
Apr 8, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Oct 25, 2019
Results First Submitted that Met QC Criteria
Dec 6, 2019
Results First Posted Date
Dec 24, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Oct 19, 2018
Certification/Extension First Submitted that Passed QC Review
Oct 19, 2018
Certification/Extension First Posted Date
Oct 23, 2018Actual
Last Update Submitted Date
Sep 15, 2022
Last Update Posted Date
Sep 28, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
IpsenINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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).
Detailed Description
Not provided
Conditions Module
Conditions
Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
212Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Group A
Experimental
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
Group B
Experimental
Group B - Treatments 1, 2, 3 and 4: Dysport 8 U/kg in one upper extremity (the study limb).
Biological: Botulinum toxin type A
Group C
Experimental
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
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Botulinum toxin type A
Biological
Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.
Group A
Group B
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG
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.
Baseline (TC 1, Day 1) and TC 1, Week 6.
Secondary Outcomes
Measure
Description
Time Frame
Mean Physician's Global Assessment (PGA) Score at 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.
Other Outcomes
Measure
Description
Time Frame
Mean Change From Baseline to TC 1 Week 16 in MAS Score in the TC 1 PTMG
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.
Eligibility Module
Eligibility Criteria
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
Delgado MR, Tilton A, Carranza-Del Rio J, Dursun N, Bonikowski M, Aydin R, Maciag-Tymecka I, Oleszek J, Dabrowski E, Grandoulier AS, Picaut P; Dysport in PUL study group. Efficacy and safety of abobotulinumtoxinA for upper limb spasticity in children with cerebral palsy: a randomized repeat-treatment study. Dev Med Child Neurol. 2021 May;63(5):592-600. doi: 10.1111/dmcn.14733. Epub 2020 Nov 18.
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.
Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
Types
Not provided
Time Frame
Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
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.
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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Dysport 2 U/kg
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.
Periods
Title
Milestones
Reasons Not Completed
Treatment Cycle 1
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jul 24, 2017
Oct 24, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Group C
AbobotulinumtoxinA (Dysport®)
TC 1, Week 6.
Mean Goal Attainment Scale (GAS) Total Score at 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.
TC 1, Week 6.
Baseline (TC 1, Day 1) and TC 1, Week 16.
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Elbow Flexors of the Study Limb
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.
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Wrist Flexors of the Study Limb
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.
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Finger Flexors of the Study Limb
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.
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
Mean PGA Score at 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.
Baseline (TC 1, Day 1) and TC 1, Week 16.
Mean GAS Total Score at 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.
Baseline (TC 1, Day 1) and TC 1, Week 16.
Mean Change From Baseline to TC 1, Week 16 in the Paediatric Quality of Life (PedsQL) Scores
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.
Baseline (TC 1, Day 1) and TC 1, Week 16.
Washington D.C.
District of Columbia
United States
New Orleans
Louisiana
United States
Royal Oak
Michigan
United States
Saint Paul
Minnesota
United States
Omaha
Nebraska
United States
Albuquerque
New Mexico
United States
New York
New York
United States
Columbus
Ohio
United States
Portland
Oregon
United States
Austin
Texas
United States
Dallas
Texas
United States
Brussels
Belgium
Brno
Czechia
Prague
Czechia
Beersheba
Israel
Jerusalem
Israel
Petah Tikva
Israel
Tel Aviv
Israel
Tel Litwinsky
Israel
La Paz
Baja California Sur
Mexico
Celaya
Mexico
Monterrey
Mexico
Gdansk
Poland
Poznan
Poland
Wiązowna
Poland
Barcelona
Spain
Terrassa
Spain
Istanbul
Turkey (Türkiye)
Izmir
Turkey (Türkiye)
Kocaeli
Turkey (Türkiye)
Derived
Shierk A, Jimenez-Moreno AC, Roberts H, Ackerman-Laufer S, Backer G, Bard-Pondarre R, Cekmece C, Pyrzanowska W, Vilain C, Delgado MR. Development of a Pediatric Goal-Centered Upper Limb Spasticity Home Exercise Therapy Program for Use in a Phase-III Trial of Abobotulinumtoxina (Dysport(R)). Phys Occup Ther Pediatr. 2019;39(2):124-135. doi: 10.1080/01942638.2018.1486346. Epub 2018 Sep 11.
FG001
Dysport 8 U/kg
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.
FG002
Dysport 16 U/kg
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.
FG00071 subjects
FG00170 subjects
FG00271 subjects
Received Treatment in TC 1
FG00070 subjects
FG00170 subjects
FG00270 subjects
COMPLETED
FG00066 subjects
FG00167 subjects
FG00267 subjects
NOT COMPLETED
FG0005 subjects
FG0013 subjects
FG0024 subjects
Type
Comment
Reasons
Adverse Event
FG0002 subjects
FG0010 subjects
FG0020 subjects
Consent withdrawn
FG0001 subjects
FG0010 subjects
FG0022 subjects
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0020 subjects
Other
FG0000 subjects
FG0013 subjects
FG0021 subjects
Randomised but not treated
FG0001 subjects
FG0010 subjects
FG0021 subjects
Treatment Cycle 2
Type
Comment
Milestone Data
STARTED
FG0000 subjectsSubjects who received Dysport 2 U/kg in TC 1 were randomised to receive 8 or 16 U/kg in TCs 2-4.
FG00188 subjectsNot all subjects who completed TC 1 required retreatment in TC 2.
FG00290 subjectsNot all subjects who completed TC 1 required retreatment in TC 2.
COMPLETED
FG0000 subjects
FG00183 subjects
FG00287 subjects
NOT COMPLETED
FG0000 subjects
FG0015 subjects
FG0023 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0012 subjects
FG0020 subjects
Consent withdrawn
FG000
Treatment Cycle 3
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG00149 subjectsNot all subjects who completed TC 2 required retreatment in TC 3.
FG00258 subjectsNot all subjects who completed TC 2 required retreatment in TC 3.
COMPLETED
FG0000 subjects
FG00145 subjects
FG00253 subjects
NOT COMPLETED
FG0000 subjects
FG0014 subjects
FG0025 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
Consent withdrawn
FG000
Treatment Cycle 4
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG00122 subjectsNot all subjects who completed TC 3 required retreatment in TC 4.
FG00233 subjectsNot all subjects who completed TC 3 required retreatment in TC 4.
COMPLETED
FG0000 subjects
FG00121 subjects
FG00231 subjects
NOT COMPLETED
FG0000 subjects
FG0011 subjects
FG0022 subjects
Type
Comment
Reasons
Consent withdrawn
FG0000 subjects
FG0010 subjects
FG0022 subjects
Other
FG000
Baseline characteristics are presented for the safety population, which consisted of all randomised subjects who received at least 1 injection of the study treatment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Dysport 2 U/kg
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).
BG001
Dysport 8 U/kg
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.
BG002
Dysport 16 U/kg
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.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00070
BG00170
BG00270
BG003210
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG0008.91± 4.55
BG0018.97± 4.27
BG0029.17± 4.30
BG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
2 - 9 Years
Title
Measurements
BG00040
BG00140
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00032
BG00124
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Asian
Title
Measurements
BG0002
BG0011
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00016
BG00113
BG002
BTX Status
Count of Participants
Participants
Title
Denominators
Categories
BTX naïve
Title
Measurements
BG00025
BG00123
BG002
Baseline MAS Score in the PTMG
The MAS has 6 grades ranging from 0 to 4 with higher scores indicate greater muscle tone. Where, 0 = no increase in muscle tone, 1 = slight increase in muscle tone, manifested by a catch + release or minimal resistance at end of range of motion (ROM), 1+ = slight increase in muscle tone, manifested by a catch and then minimal resistance throughout remainder (less than half) of ROM, 2 = more marked increase in muscle tone, 3 = considerable increase in muscle tone and 4 = affected part(s) rigid in flexion/extension. '1+' was given a derived score of '2'; following scores were incremented by 1.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
Title
Measurements
BG0003.1± 0.3
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Baseline (TC 1, Day 1) and TC 1, Week 6.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
OG001
Dysport 8 U/kg
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.
OG002
Dysport 16 U/kg
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.
Units
Counts
Participants
OG00069
OG00169
OG00270
Title
Denominators
Categories
Title
Measurements
OG000-1.5± 1.1
OG001-1.9± 1.0
OG002-2.2± 0.9
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
ANCOVA
ANCOVA is performed on the ranked values.
0.0118
The 2-tailed significance level was 0.05.
LS mean difference back transformed
-0.4
2-Sided
Secondary
Mean Physician's Global Assessment (PGA) Score at 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.
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.
Posted
Mean
Standard Deviation
score on a scale
TC 1, Week 6.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
OG001
Dysport 8 U/kg
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.
OG002
Dysport 16 U/kg
Secondary
Mean Goal Attainment Scale (GAS) Total Score at 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.
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.
Posted
Mean
Standard Deviation
T-score
TC 1, Week 6.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
OG001
Other Pre-specified
Mean Change From Baseline to TC 1 Week 16 in MAS Score in the TC 1 PTMG
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Baseline (TC 1, Day 1) and TC 1, Week 16.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
OG001
Dysport 8 U/kg
Other Pre-specified
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Elbow Flexors of the Study Limb
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
Other Pre-specified
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Wrist Flexors of the Study Limb
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
Other Pre-specified
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Finger Flexors of the Study Limb
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
Other Pre-specified
Mean PGA Score at 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.
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.
Posted
Mean
Standard Deviation
score on a scale
Baseline (TC 1, Day 1) and TC 1, Week 16.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
OG001
Dysport 8 U/kg
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.
OG002
Dysport 16 U/kg
Other Pre-specified
Mean GAS Total Score at 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.
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.
Posted
Mean
Standard Deviation
T-score
Baseline (TC 1, Day 1) and TC 1, Week 16.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
Other Pre-specified
Mean Change From Baseline to TC 1, Week 16 in the Paediatric Quality of Life (PedsQL) Scores
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Baseline (TC 1, Day 1) and TC 1, Week 16.
ID
Title
Description
OG000
Dysport 2 U/kg
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).
OG001
Dysport 8 U/kg
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.
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).
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.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
TC1: Dysport 2 U/kg
Subjects randomised to Dysport 2 U/kg in TC 1.
0
70
4
70
15
70
EG001
TC 1: Dysport 8 U/kg
Subjects randomised to Dysport 8 U/kg in TC 1.
0
70
2
70
23
70
EG002
TC 1: Dysport 16 U/kg
Subjects randomised to Dysport 16 U/kg in TC 1.
0
70
2
70
19
70
EG003
TC 2: Dysport 8 U/kg
Subjects who received Dysport 8 U/kg in TC 2.
0
88
6
88
18
88
EG004
TC 2: Dysport 16 U/kg
Subjects who received Dysport 16 U/kg in TC 2.
0
90
1
90
17
90
EG005
TC 3: Dysport 8 U/kg
Subjects who received Dysport 8 U/kg in TC 3.
0
49
3
49
14
49
EG006
TC 3: Dysport 16 U/kg
Subjects who received Dysport 16 U/kg in TC 3.
0
58
2
58
10
58
EG007
TC 4: Dysport 8 U/kg
Subjects who received Dysport 8 U/kg in TC 4.
0
22
2
22
14
22
EG008
TC 4: Dysport 16 U/kg
Subjects who received Dysport 16 U/kg in TC 4.
0
33
1
33
5
33
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Epilepsy
Nervous system disorders
MedDRA v 20.0
Systematic Assessment
EG0000 events0 affected70 at risk
EG0010 events0 affected70 at risk
EG0021 events1 affected70 at risk
EG0030 events0 affected88 at risk
EG0040 events0 affected90 at risk
EG0050 events0 affected49 at risk
EG0062 events2 affected58 at risk
EG0070 affected22 at risk
EG0080 affected33 at risk
Focal dyscognitive seizures
Nervous system disorders
MedDRA v 20.0
Systematic Assessment
EG0000 events0 affected70 at risk
EG0010 events0 affected70 at risk
EG0021 events1 affected70 at risk
EG003
Cerebral ventricle dilatation
Nervous system disorders
MedDRA v 20.0
Systematic Assessment
EG0000 events0 affected70 at risk
EG0011 events1 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Seizure
Nervous system disorders
MedDRA v 20.0
Systematic Assessment
EG0001 events1 affected70 at risk
EG0010 events0 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Depression
Psychiatric disorders
MedDRA v 20.0
Systematic Assessment
EG0000 events0 affected70 at risk
EG0011 events1 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA v 20.0
Systematic Assessment
EG0001 events1 affected70 at risk
EG0010 events0 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA v 20.0
Systematic Assessment
EG0001 events1 affected70 at risk
EG0010 events0 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA v 20.0
Systematic Assessment
EG0001 events1 affected70 at risk
EG0010 events0 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Appendicitis
Infections and infestations
MedDRA v 20.0
Systematic Assessment
EG0000 events0 affected70 at risk
EG0010 events0 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Escherichia urinary tract infection
Infections and infestations
MedDRA v 20.0
Systematic Assessment
EG0000 events0 affected70 at risk
EG0010 events0 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA v 20.0
Systematic Assessment
EG0000 events0 affected70 at risk
EG0010 events0 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Influenza
Infections and infestations
MedDRA v 20.0
Systematic Assessment
EG0000 events0 affected70 at risk
EG0010 events0 affected70 at risk
EG0020 events0 affected70 at risk
EG003
Testicular malignant teratoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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.
ANCOVA
ANCOVA is performed on the ranked values.
<0.0001
The 2-tailed significance level was 0.05.
LS mean difference back transformed
-0.7
2-Sided
Superiority
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.
Units
Counts
Participants
OG00068
OG00169
OG00270
Title
Denominators
Categories
Title
Measurements
OG0001.7± 0.9
OG0012.0± 0.9
OG0022.0± 0.9
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
ANOVA
ANOVA was performed on ranked values.
0.2043
The two-tailed significance level was 0.05.
LS mean difference back transformed
0.2
2-Sided
Superiority
OG000
OG002
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.
ANOVA
ANOVA was performed on ranked values.
0.1880
The two-tailed significance level was 0.05.
LS mean difference back transformed
0.2
2-Sided
Superiority
Dysport 8 U/kg
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.
OG002
Dysport 16 U/kg
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.
Units
Counts
Participants
OG00068
OG00166
OG00270
Title
Denominators
Categories
Title
Measurements
OG00051.3± 9.9
OG00152.6± 10.1
OG00252.0± 9.6
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
ANOVA
0.7648
The two-tailed significance level was 0.05.
LS mean difference
0.5
2-Sided
95
-2.7
3.7
Superiority
OG000
OG002
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.
ANOVA
0.7429
The two-tailed significance level was 0.05.
LS mean difference
0.5
2-Sided
95
-2.6
3.7
Superiority
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.
OG002
Dysport 16 U/kg
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.
Units
Counts
Participants
OG00068
OG00168
OG00268
Title
Denominators
Categories
Title
Measurements
OG000-1.0± 1.0
OG001-1.4± 1.1
OG002-1.6± 1.2
OG001
Dysport 8 U/kg
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.
OG002
Dysport 16 U/kg
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.
Units
Counts
Participants
OG00069
OG00169
OG00270
Title
Denominators
Categories
Week 6
ParticipantsOG00063
ParticipantsOG00163
ParticipantsOG00262
Title
Measurements
OG000-1.0± 1.1
OG001-1.7± 1.1
OG002-1.9± 1.2
Week 16
ParticipantsOG00062
ParticipantsOG00162
ParticipantsOG00260
Title
Measurements
OG000
OG001
Dysport 8 U/kg
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.
OG002
Dysport 16 U/kg
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.
Units
Counts
Participants
OG00069
OG00169
OG00270
Title
Denominators
Categories
Week 6
ParticipantsOG00050
ParticipantsOG00153
ParticipantsOG00261
Title
Measurements
OG000-1.3± 1.1
OG001-1.5± 1.2
OG002-1.7± 1.3
Week 16
ParticipantsOG00050
ParticipantsOG00153
ParticipantsOG00259
Title
Measurements
OG000
OG001
Dysport 8 U/kg
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.
OG002
Dysport 16 U/kg
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.
Units
Counts
Participants
OG00069
OG00169
OG00270
Title
Denominators
Categories
Week 6
ParticipantsOG00023
ParticipantsOG00123
ParticipantsOG00219
Title
Measurements
OG000-0.8± 0.9
OG001-1.8± 1.1
OG002-1.9± 1.0
Week 16
ParticipantsOG00022
ParticipantsOG00123
ParticipantsOG00219
Title
Measurements
OG000
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.
Units
Counts
Participants
OG00069
OG00169
OG00270
Title
Denominators
Categories
Title
Measurements
OG0001.7± 1.0
OG0011.6± 1.1
OG0021.9± 1.2
OG001
Dysport 8 U/kg
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.
OG002
Dysport 16 U/kg
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.
Units
Counts
Participants
OG00069
OG00169
OG00270
Title
Denominators
Categories
Title
Measurements
OG00054.7± 9.8
OG00154.2± 9.7
OG00255.1± 10.1
OG002
Dysport 16 U/kg
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.