Clinical Trial Results:
A phase III, multicentre, prospective, open label extension study to assess the long term safety and efficacy of repeated treatment of Dysport intramuscular injections used for the treatment of upper limb spasticity in adult subjects with spastic hemiparesis due to stroke or traumatic brain injury
Summary
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EudraCT number |
2010-019162-83 |
Trial protocol |
BE CZ SK PL IT HU |
Global end of trial date |
09 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
15 May 2016
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First version publication date |
15 May 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
Y-52-52120-148
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Ipsen Innovation
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Sponsor organisation address |
5 Avenue du Canada, Les Ulis, France, 91940
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Public contact |
Medical Director, Neurology., Ipsen Innovation, clinical.trials@ipsen.com
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Scientific contact |
Medical Director, Neurology., Ipsen Innovation, clinical.trials@ipsen.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Dec 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Dec 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary study objective is to assess the long term safety of Dysport in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury over repeated treatment cycles.
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Protection of trial subjects |
This clinical study was designed and implemented and reported in accordance with the International Conference on Harmonisation (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Nov 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Russian Federation: 19
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Country: Number of subjects enrolled |
United States: 101
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Country: Number of subjects enrolled |
Poland: 33
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Country: Number of subjects enrolled |
Slovakia: 8
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Country: Number of subjects enrolled |
Belgium: 18
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Country: Number of subjects enrolled |
Czech Republic: 24
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Country: Number of subjects enrolled |
France: 36
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Country: Number of subjects enrolled |
Hungary: 12
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Country: Number of subjects enrolled |
Italy: 7
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Worldwide total number of subjects |
258
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EEA total number of subjects |
138
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
204
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From 65 to 84 years |
54
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was designed as a multicentre study and included 34 investigational sites in Belgium, the Czech Republic, France, Hungary, Italy, Poland, Russia, Slovakia and the United States of America (US) that included at least one subject. | ||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Of 227 subjects who completed Study 145, 4 subjects entered observational phase and never received open label treatment with Dysport in Study 148. Remaining 223 subjects were eligible for retreatment and were rolled over to study 148. In addition, of 34 de novo subjects screened, 31 subjects were eligible and included in this study. | ||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
Arms
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Arm title
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Total Dysport | ||||||||||||||||||||||||||||
Arm description |
Of 227 subjects who completed study 145, 223 Subjects rolled over to this study (4 subjects entered an observational phase at the end of Study 145). Of 34 subjects screened for De-Novo study, only 31 were treated with open label Botulinum type A toxin (Dysport) dose of 1000 Units (U) in Cycle 1 and from Cycle 2 onwards Dysport 500 / 1000 / 1500 U | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Dysport
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
A vials containing 500 U of botulinum toxin type A reconstituted with sodium chloride 5.0 ml for 500 U and 1000 U Dysport, and 7.5ml for 1500U Dysport Intramuscular injection.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Worldwide data is reported for safety population of 258 subjects and baseline data is reported for 254 subjects for ITT population (this excludes 4 subjects who entered observational phase in study 148 and never received open label treatment with Dysport in Study 148). [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Of 254 subjects who started in cycle 1, only 175 subjects entered cycle 3. (24 subjects withdrew at cycles 1 & 2, 54 subjects ended study after 12 months follow-up and 1 subject entered observational phase) [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Of 254 subjects who started in cycle 1, only 81 subjects entered cycle 4. (30 subjects withdrew at cycles 1, 2 & 3, 142 subjects ended study after 12 months follow-up and 1 subject entered observational phase) [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Of 254 subjects who started in cycle 1, only 11 subjects entered cycle 5. (31 subjects withdrew at cycles 1 ,2, 3 & 4, 211 subjects ended study after 12 months follow-up and 1 subject entered observational phase) |
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Baseline characteristics reporting groups
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Reporting group title |
Total Dysport
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Reporting group description |
Of 227 subjects who completed study 145, 223 Subjects rolled over to this study (4 subjects entered an observational phase at the end of Study 145). Of 34 subjects screened for De-Novo study, only 31 were treated with open label Botulinum type A toxin (Dysport) dose of 1000 Units (U) in Cycle 1 and from Cycle 2 onwards Dysport 500 / 1000 / 1500 U | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Total Dysport
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Reporting group description |
Of 227 subjects who completed study 145, 223 Subjects rolled over to this study (4 subjects entered an observational phase at the end of Study 145). Of 34 subjects screened for De-Novo study, only 31 were treated with open label Botulinum type A toxin (Dysport) dose of 1000 Units (U) in Cycle 1 and from Cycle 2 onwards Dysport 500 / 1000 / 1500 U |
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End point title |
Assessment of the long term safety of Treatment Emergent Adverse Events [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TEAEs (treatment emergent adverse event)
AESIs (adverse event of special interest)
SAEs (serious adverse event)
Safety population are all enrolled subjects who provided informed consent to participate in this open label study.
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in Diastolic and Systolic BP [2] | ||||||||||||
End point description |
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in Heart Rate [3] | ||||||||||
End point description |
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in RBC count [4] | ||||||||||
End point description |
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in Haemoglobin and MCHC [5] | ||||||||||||
End point description |
MCHC (mean corpuscular haemoglobin concentration)
Haematology Variables
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in Haematocrit [6] | ||||||||||
End point description |
Haematology Variables
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in MCH [7] | ||||||||||
End point description |
MCH (mean corpuscular haemoglobin)
Haematology Variables
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in MCV [8] | ||||||||||
End point description |
MCV (mean corpuscular volume)
Haematology Variables
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in WBC count, Neutrophils, Lymphocytes and Platelets [9] | ||||||||||||||||
End point description |
WBC (white blood cell)
Haematology Variables
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean change from baseline to end of study (EOS)/early withdrawal in 12 lead Electrocardiogram (ECG) [10] | ||||||||||||||||||||||||||||
End point description |
Safety population
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in ALP, SGOT, SGPT and GGT [11] | ||||||||||||||||
End point description |
ALP=alkaline phosphatase; GGT=gamma glutamyl transferase; SGOT=serum glutamic oxaloacetic transaminase; SGPT=serum glutamic pyruvic transaminase.
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in Total Bilirubin and Creatinine [12] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline to End of Study/Early Withdrawal in BUN and Fasting Blood Glucose [13] | ||||||||||||
End point description |
BUN=blood urea nitrogen
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean change from baseline to end of study/early withdrawal in 12 lead ECG - Heart Rate [14] | ||||||||||||
End point description |
Safety population
EOS= End of Study
bpm = beats per minute
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Number of subjects with Botulinum Toxin A Binding and Neutralising Putative Antibodies [15] | ||||||||||||||
End point description |
Number of subjects who were positive / Negative at baseline and positive post baseline for binding and neutralizing
Safety population
+ve = positive
-ve = negative
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End point type |
Primary
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End point timeframe |
Up to visit V20 (week 52)
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Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses for this endpoint |
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No statistical analyses for this end point |
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End point title |
Mean change from baseline MAS in the overall PTMG for upper limb | ||||||||||||||||||
End point description |
The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second.
The intention to treat (ITT) population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study.
PTMG (Primary Targeted Muscle Group)
MAS (Modified Ashworth Scale Score)
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End point type |
Secondary
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End point timeframe |
At week 4 (visit 2)
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No statistical analyses for this end point |
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End point title |
Percentage of subjects with at least one grade reduction in MAS for overall PTMG | ||||||||||||||||||
End point description |
ITT population.
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Physicians Global Assessment of Treatment Response | ||||||||||||||||||
End point description |
Physician’s Global Assessment is 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, +4=markedly improved.
ITT population
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Mean change from baseline in Disability Assessment Scale Score for the Principal Target of Treatment | ||||||||||||||||||
End point description |
Disability Assessment Scale is a 4-point scale, the extent of functional impairment in four functional domains (dressing, hygiene, limb position and pain) was rated as follows: 0=no disability, 1=mild disability (noticeable but does not interfere significantly with normal activities), 2=moderate disability (normal activities require increased effort and/or assistance) and 3=severe disability (normal activities limited).
ITT population
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Percentage of subjects with at least one grade reduction in DAS for PTT | ||||||||||||||||||
End point description |
ITT population
DAS (Disability Assessment Scale)
PTT (Principal Target of Treatment)
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Mean change from baseline for X (angle of spasticity) of the TS in extrinsic finger flexors as PTMG | ||||||||||||||||||
End point description |
The TS was used to measure spasticity in the shoulder extensors, elbow flexors, wrist flexors and extrinsic finger flexors. Assessments were made at slow (V1) and fast (V3) speeds of stretch. The angle of arrest at slow speed (XV1), the angle of catch at fast speed (XV3) and the spasticity grade (Y) at fast speed were recorded in the eCRF. The spasticity angle was automatically calculated in the eCRF as the difference between the angle of arrest at slow speed (XV1) and the angle of catch at fast speed (XV3). The spasticity grade (Y) is an ordinal variable that grades the intensity of the muscle reaction to fast stretch.
TS (Tardieu Scale)
PTMG (Primary Targeted Muscle group)
ITT population
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Mean change from baseline for X (angle of spasticity) of the TS in elbow flexors as PTMG | ||||||||||||||||||
End point description |
ITT population
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Mean change from baseline for X (angle of spasticity) of the TS in wrist flexors as PTMG | ||||||||||||||||||
End point description |
ITT population
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Mean change from baseline in active range of motion (AROM) in the 3 possible PTMGs | ||||||||||||||||||||||||||||||||||||||
End point description |
ITT population
The active range of extension achieved by the subjects moving each joint without assistance was measured at baseline and at all subsequent study visits during each cycle. A goniometer was used for measurements in the elbow and wrist flexors but not for measurements in the extrinsic finger flexors.
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Mean change from baseline in Ease of Applying a Splint | ||||||||||||||||||
End point description |
The ease of applying a splint was evaluated on a 6-point scale (0: no splint needed, –1: splint needed and applied with no difficulty, –2: splint needed and applied with mild difficulty, –3: splint needed and applied with moderate difficulty, –4: splint needed and applied with severe difficulty, –5: splint needed, but unable to apply).
ITT population
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Mean change from baseline in Modified Frenchay Scale (MFS) | ||||||||||||||||||
End point description |
ITT population
The MFS was used to measure upper limb active function. Each subject was videotaped while performing specific tasks. The videos were sent to a central provider and were read and scored by two independent readers blinded to the timing of the video and to treatment. These central assessments were used for the analysis of efficacy endpoints
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Short Form (36) Health Survey (SF-36) Quality of Life | ||||||||||||||||||||||||
End point description |
ITT population
Subjects were asked to complete the SF 36 questionnaires prior to the study treatment at baseline and at the end of study/early withdrawal visit. The SF 36 is a generic nonpreference based health status measure. This instrument assessed subject health across eight dimensions, which are specific health domains such as physical functioning, social functioning and vitality.
Physical Component Summary (PCS); Mental Component Summary (MCS); Change = Change from Baseline
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End point type |
Secondary
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End point timeframe |
Baseline (Cycle 1 Day 1) and Final visit (up to year 1)
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Quality of Life | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
ITT population
Subjects were asked to complete the EQ 5D Quality of Life (QoL) questionnaires prior to the study treatment at baseline and at the end of study/early withdrawal visit. The EQ 5D index is a generic preference based measure of health related QoL producing utility scores that represent subject preferences for particular health states. This instrument rated subject health state looking at five specific dimensions such as mobility, self-care, usual activity, pain/discomfort and anxiety/depression and scored their general health state.
Double Blind (DB); Open Label (OL); Visual Analogue Scale (VAS); Change = Change from Baseline
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End point type |
Secondary
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End point timeframe |
Baseline (Cycle 1 Day 1) and Final visit (up to year 1)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Up to visit 20 (week 52)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Total Dysport
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Reporting group description |
223 Subjects who rolled over from study 145 plus 31 subjects from observational De-Novo study entered this open label Botulinum type A toxin (Dysport) dose of 1000 Units (U) in Cycle 1 and from Cycle 2 onwards Dysport 500 / 1000 / 1500 U | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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09 Feb 2012 |
Protocol Amendment 2 - Made the following changes:
•The sponsor’s Medically Responsible Person was changed.
•Pronator muscles were excluded from the MAS and TS assessments.
•The study entry criteria was simplified to exclude subjects who had undergone previous surgery to treat spasticity of the affected upper limb (instead of those who had received previous surgery on muscles, ligaments, tendons, nerve trunks or bones of the upper limb).
•A new exclusion criterion was added to exclude treatment with intrathecal baclofen during the course of the study.
•Subjects not requiring a new treatment cycle at the Week 24 follow up visit of Treatment Cycle 1 or 2 (instead of Cycle 1 and potentially Cycle 2) were required to have follow up visits every 4 weeks until a new treatment cycle was required or they reached 12 months follow up.
•The Central Laboratory was changed.
•12-lead ECG was to be recorded after 5 minutes rest instead of after 30 minutes rest.
•Section 9.6 concerning dosage of concomitant medications was amended to include oral baclofen.
•Item 9 of the Modified Frenchay Scale was altered to specify that the affected hand was to hold the fork for this task. |
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25 Apr 2013 |
Protocol Amendment 4 - Made the following changes:
•The Sponsor’s Co-ordinating and Monitoring Officer was changed.
•The protocol was substantially updated to include de novo patients as well as rollover subjects from Study 145. The changes specified included:
-The study design was amended to include the definition of baseline for MAS de novo patients, the maximum number of treatment cycles in the extension study for the rollover and de novo subjects, the start time of the first treatment cycle for the two populations and the maximum study duration.
-Separate inclusion criteria were provided for rollover and de novo subjects
-The start of the observation period was specified separately for rollover and de novo subjects.
-A separate definition was provided for the selection of primary targeted muscle groups in the de novo subjects.
-Separate schedules of assessment were defined for de novo and rollover subjects.
-Separate conditions were defined for rollover and de novo subjects who required injections within 2 weeks of the Week 12 visit of any treatment cycle.
-Separate study flow diagrams were provided for rollover and de novo subjects. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |