Trial Outcomes & Findings for Dysport® Adult Upper Limb Spasticity Extension Study (NCT NCT01313312)
NCT ID: NCT01313312
Last Updated: 2022-09-28
Results Overview
A TEAE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any adverse event (AE) that was assessed as a hypersensitivity reaction. TEAEs, AESIs, severe TEAEs, serious adverse events (SAEs), treatment related TEAEs, TEAEs leading to withdrawal and fatal SAEs are summarised by treatment cycle.
COMPLETED
PHASE3
258 participants
Up to Week 52
2022-09-28
Participant Flow
The study was designed as a multicentre study and included a total of 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. This study was an open label extension to the double blind Study 145 (Y-52-52120-145).
Of 227 subjects who completed Study 145, 4 subjects entered an observational phase and never received treatment with Dysport® in this open label extension study (Study 148). The remaining 223 subjects were eligible for retreatment and progressed to Study 148. In addition, 31 of the 34 de novo subjects screened were included in this study.
Participant milestones
| Measure |
Total Dysport®
A total of 254 subjects in the open label study received between 1 and 5 intramuscular (i.m.) injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Overall Study
STARTED
|
258
|
|
Overall Study
Cycle 1
|
254
|
|
Overall Study
Cycle 2
|
229
|
|
Overall Study
Cycle 3
|
175
|
|
Overall Study
Cycle 4
|
81
|
|
Overall Study
Cycle 5
|
11
|
|
Overall Study
COMPLETED
|
222
|
|
Overall Study
NOT COMPLETED
|
36
|
Reasons for withdrawal
| Measure |
Total Dysport®
A total of 254 subjects in the open label study received between 1 and 5 intramuscular (i.m.) injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Withdrawal by Subject
|
18
|
|
Overall Study
Lack of Efficacy
|
3
|
|
Overall Study
Investigator Decision
|
1
|
|
Overall Study
Observational Phase
|
1
|
|
Overall Study
Subject Withdrawn Early in Error
|
4
|
|
Overall Study
Did Not Receive Treatment with Dysport®
|
4
|
Baseline Characteristics
Dysport® Adult Upper Limb Spasticity Extension Study
Baseline characteristics by cohort
| Measure |
Total Dysport®
n=254 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
201 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
53 Participants
n=5 Participants
|
|
Age, Continuous
|
52.4 years
STANDARD_DEVIATION 14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
91 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
163 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
238 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
218 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
A TEAE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any adverse event (AE) that was assessed as a hypersensitivity reaction. TEAEs, AESIs, severe TEAEs, serious adverse events (SAEs), treatment related TEAEs, TEAEs leading to withdrawal and fatal SAEs are summarised by treatment cycle.
Outcome measures
| Measure |
Total Dysport®
n=254 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs: Cycle 1
|
102 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs: Cycle 2
|
62 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs: Cycle 3
|
47 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs: Cycle 4
|
11 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs: Cycle 5
|
2 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Treatment related TEAE: Cycle 1
|
18 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Treatment related TEAE: Cycle 2
|
8 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Treatment related TEAE: Cycle 3
|
5 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Treatment related TEAE: Cycle 4
|
2 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Treatment related TEAE: Cycle 5
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Severe TEAEs: Cycle 1
|
14 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Severe TEAEs: Cycle 2
|
8 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Severe TEAEs: Cycle 3
|
4 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Severe TEAEs: Cycle 4
|
1 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Severe TEAEs: Cycle 5
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs Leading to Withdrawal: Cycle 1
|
2 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs Leading to Withdrawal: Cycle 2
|
1 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs Leading to Withdrawal: Cycle 3
|
2 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs Leading to Withdrawal: Cycle 4
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
TEAEs Leading to Withdrawal: Cycle 5
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
AESIs: Cycle 1
|
2 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
AESIs: Cycle 2
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
AESIs: Cycle 3
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
AESIs: Cycle 4
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
AESIs: Cycle 5
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
SAEs: Cycle 1
|
10 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
SAEs: Cycle 2
|
6 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
SAEs: Cycle 3
|
6 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
SAEs: Cycle 4
|
1 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
SAEs: Cycle 5
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Fatal SAEs: Cycle 1
|
1 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Fatal SAEs: Cycle 2
|
1 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Fatal SAEs: Cycle 3
|
1 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Fatal SAEs: Cycle 4
|
0 Participants
|
|
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)
Fatal SAEs: Cycle 5
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Systolic and diastolic BP were recorded at screening, baseline and at each post baseline visit. Vital signs were measured with the subject in a sitting position after resting for 3 minutes. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=238 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Diastolic and Systolic Blood Pressure (BP)
Diastolic BP
|
0 Millimeters of Mercury (mm Hg)
Interval -29.0 to 34.0
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Diastolic and Systolic Blood Pressure (BP)
Systolic BP
|
-2.8 Millimeters of Mercury (mm Hg)
Interval -63.0 to 41.0
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
HR was recorded at screening, baseline and at each post baseline visit. Vital signs were measured with the subject in a sitting position after resting for 3 minutes. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=239 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Heart Rate (HR)
|
2.5 Beats per minute (bpm)
Interval -28.0 to 30.0
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for RBC count were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=219 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Red Blood Cell (RBC) Count
|
0.03 Tera cells/Litre (L)
Interval -1.15 to 1.06
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for haemoglobin and MCHC were taken at baseline, at post treatment follow up visit Week 4, and at the end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=219 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)
Haemoglobin
|
-0.7 grams(g)/L
Interval -33.0 to 37.0
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)
MCHC
|
-0.8 grams(g)/L
Interval -26.0 to 34.0
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for haematocrit were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=219 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Haematocrit
|
-0.0011 percentage of RBC in blood
Interval -0.104 to 0.087
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for MCH were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=219 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Haemoglobin (MCH)
|
-0.33 picograms (pg)
Interval -5.0 to 4.9
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for MCV were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=219 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Volume (MCV)
|
-0.77 femtoliters (fL)
Interval -9.9 to 8.2
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for WBC count with differentials (neutrophils, lymphocytes) and platelet count were taken at baseline, at post treatment follow up visit Week 4, and at end of study or early withdrawal.
Outcome measures
| Measure |
Total Dysport®
n=219 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets
Lymphocytes
|
0.01 Giga cells/L
Interval -1.9 to 1.2
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets
Platelets
|
3.2 Giga cells/L
Interval -142.0 to 249.0
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets
WBC count
|
0.04 Giga cells/L
Interval -6.5 to 5.2
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets
Neutrophils
|
0 Giga cells/L
Interval -6.8 to 5.6
|
PRIMARY outcome
Timeframe: Up to Week 52Population: The ECG analysis was performed in the safety population among subjects who had at least one ECG measurement before injection and at least one ECG after injection. Only subjects with data available for analysis at the point of testing are reported.
12-lead ECG tracing was performed at baseline, post treatment at Week 4 and at the end of study/early withdrawal visit. The 12-lead ECG recordings were performed at a paper speed of 25 mm/s, recorded with the subject in a supine position after 5 minutes rest. The ECG parameters reported were QRS duration, PR duration, QT duration, QTcB (QT interval corrected for HR according to Bazett), and QTcF (QT interval corrected for HR according to Fridericia) at baseline and the change to end of study/early withdrawal visit (EOS).
Outcome measures
| Measure |
Total Dysport®
n=235 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
QT Duration - Baseline
|
403.6 milliseconds (ms)
Standard Deviation 31.9
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
QT Duration - Change from Baseline to EOS
|
-6.3 milliseconds (ms)
Standard Deviation 22.1
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
QTcF - Baseline
|
417.8 milliseconds (ms)
Standard Deviation 22.9
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
QTcF - Change from Baseline to EOS
|
-1 milliseconds (ms)
Standard Deviation 15.5
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
QTcB - Baseline
|
425.6 milliseconds (ms)
Standard Deviation 25.5
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
QTcB - Change from Baseline to EOS
|
1.9 milliseconds (ms)
Standard Deviation 20.2
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
QRS Duration - Baseline
|
94.9 milliseconds (ms)
Standard Deviation 15.3
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
QRS Duration - Change from Baseline to EOS
|
-0.4 milliseconds (ms)
Standard Deviation 6.4
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
PR Duration - Baseline
|
165.6 milliseconds (ms)
Standard Deviation 25.4
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)
PR Duration - Change from Baseline to EOS
|
-0.3 milliseconds (ms)
Standard Deviation 13.2
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for analysis of the following clinical chemistry parameters: ALP, GGT, SGOT and SGPT were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=226 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)
ALP
|
-0.6 International Unit/L (IU/L)
Interval -39.0 to 83.0
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)
SGOT
|
1.4 International Unit/L (IU/L)
Interval -32.0 to 45.0
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)
SGPT
|
1.2 International Unit/L (IU/L)
Interval -81.0 to 57.0
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)
GGT
|
1.5 International Unit/L (IU/L)
Interval -105.0 to 195.0
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for clinical chemistry analysis of total bilirubin and creatinine were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.
Outcome measures
| Measure |
Total Dysport®
n=226 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Total Bilirubin and Creatinine
Creatinine
|
-3.7 Micromole/L (μmol/L)
Interval -115.0 to 35.0
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Total Bilirubin and Creatinine
Total Bilirubin
|
-0.27 Micromole/L (μmol/L)
Interval -18.7 to 12.2
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Subjects who entered the study and received at least one open label injection of Dysport® were evaluated for safety analysis. Only subjects with data available for analysis at the point of testing are reported.
Blood samples for analysis of BUN and fasting blood glucose levels were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal.
Outcome measures
| Measure |
Total Dysport®
n=226 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose
BUN
|
-0.033 millimoles(mmol)/L
Interval -12.85 to 8.93
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose
Fasting Blood Glucose
|
0.132 millimoles(mmol)/L
Interval -3.66 to 7.94
|
PRIMARY outcome
Timeframe: Up to Week 52Population: The ECG analysis was performed in the safety population among subjects who had at least one ECG measurement before injection and at least one ECG after injection. Only subjects with data available for analysis at the point of testing are reported.
HR was measured by 12-lead ECG tracing, performed at baseline, at post treatment follow up visit Week 4, and at the end of study or early withdrawal visit. The 12-lead ECG recordings were performed at a paper speed of 25 mm/s, recorded with the subject in a supine position after 5 minutes rest.
Outcome measures
| Measure |
Total Dysport®
n=243 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12 Lead ECG - HR
Baseline
|
68.2 bpm
Standard Deviation 11.3
|
|
Mean Change From Baseline to End of Study/Early Withdrawal in 12 Lead ECG - HR
Change from Baseline to EOS
|
2.7 bpm
Standard Deviation 10.5
|
PRIMARY outcome
Timeframe: Up to Week 52Population: Binding and neutralising antibodies were evaluated at baseline for all 258 subjects (rollover and de novo) enrolled in Study 148. Only subjects with data available for analysis at the point of testing are reported.
Blood samples were collected at baseline, Week 4 of each cycle, and at the end of study/early withdrawal to test for the presence of Botulinum Toxin A Binding antibodies. Samples positive for the presence of binding antibodies were then analysed for the presence of neutralising putative antibodies. The number of subjects who were either positive (+ve) or negative (-ve) at baseline and then positive post baseline for binding or neutralising antibodies were reported.
Outcome measures
| Measure |
Total Dysport®
n=258 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Number of Subjects With Botulinum Toxin A Binding and Neutralising Putative Antibodies
Binding +ve at baseline
|
5 Participants
|
|
Number of Subjects With Botulinum Toxin A Binding and Neutralising Putative Antibodies
Binding -ve at baseline & +ve post baseline
|
20 Participants
|
|
Number of Subjects With Botulinum Toxin A Binding and Neutralising Putative Antibodies
Neutralising +ve at baseline
|
4 Participants
|
|
Number of Subjects With Botulinum Toxin A Binding and Neutralising Putative Antibodies
Neutralising -ve at baseline & +ve post baseline
|
11 Participants
|
SECONDARY outcome
Timeframe: At Week 4Population: The Intent-to-Treat (ITT) population was all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The clinical assessment of muscle tone was performed using the MAS. 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 mean changes from baseline to Week 4 in MAS in the overall PTMG (finger, wrist or elbow flexors) are reported.
Outcome measures
| Measure |
Total Dysport®
n=252 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline Modified Ashworth Scale (MAS) in the Overall Primary Targeted Muscle Group (PTMG) for Upper Limb at Week 4
Cycle 1
|
-1.4 units on a scale
Standard Deviation 1.1
|
|
Mean Change From Baseline Modified Ashworth Scale (MAS) in the Overall Primary Targeted Muscle Group (PTMG) for Upper Limb at Week 4
Cycle 2
|
-1.6 units on a scale
Standard Deviation 1.2
|
|
Mean Change From Baseline Modified Ashworth Scale (MAS) in the Overall Primary Targeted Muscle Group (PTMG) for Upper Limb at Week 4
Cycle 3
|
-1.5 units on a scale
Standard Deviation 1.1
|
|
Mean Change From Baseline Modified Ashworth Scale (MAS) in the Overall Primary Targeted Muscle Group (PTMG) for Upper Limb at Week 4
Cycle 4
|
-1.4 units on a scale
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
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 percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the overall PTMG at Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=254 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG
At least 1 grade reduction - Cycle 1
|
77.6 percentage of participants
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG
At least 1 grade reduction - Cycle 2
|
79.5 percentage of participants
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG
At least 1 grade reduction - Cycle 3
|
77.1 percentage of participants
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG
At least 1 grade reduction - Cycle 4
|
75.3 percentage of participants
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG
At least 2 grades reduction - Cycle 1
|
42.1 percentage of participants
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG
At least 2 grades reduction - Cycle 2
|
48.0 percentage of participants
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG
At least 2 grades reduction - Cycle 3
|
44.6 percentage of participants
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG
At least 2 grades reduction - Cycle 4
|
37.0 percentage of participants
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The clinical assessment of muscle tone was performed using the MAS. 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 mean changes from baseline to Week 4 in MAS in the extrinsic finger flexors are reported.
Outcome measures
| Measure |
Total Dysport®
n=220 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline MAS in the Extrinsic Finger Flexors at Week 4
Cycle 1
|
-1.3 units on a scale
Standard Deviation 1.1
|
|
Mean Change From Baseline MAS in the Extrinsic Finger Flexors at Week 4
Cycle 2
|
-1.5 units on a scale
Standard Deviation 1.2
|
|
Mean Change From Baseline MAS in the Extrinsic Finger Flexors at Week 4
Cycle 3
|
-1.5 units on a scale
Standard Deviation 1.3
|
|
Mean Change From Baseline MAS in the Extrinsic Finger Flexors at Week 4
Cycle 4
|
-1.3 units on a scale
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
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 percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the extrinsic finger flexors at Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=145 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4
At least 1 Grade Reduction -Cycle 1
|
78.6 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4
At least 1 Grade Reduction -Cycle 2
|
81.3 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4
At least 1 Grade Reduction -Cycle 3
|
80 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4
At least 1 Grade Reduction -Cycle 4
|
80.4 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4
At least 2 Grades Reduction -Cycle 1
|
44.1 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4
At least 2 Grades Reduction -Cycle 2
|
49.3 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4
At least 2 Grades Reduction -Cycle 3
|
49.5 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4
At least 2 Grades Reduction -Cycle 4
|
37.5 percentage of subjects
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The clinical assessment of muscle tone was performed using the MAS. 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 mean changes from baseline to Week 4 in MAS in the wrist flexors are reported.
Outcome measures
| Measure |
Total Dysport®
n=169 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline MAS in the Wrist Flexors at Week 4
Cycle 1
|
-1.5 units on a scale
Standard Deviation 1.2
|
|
Mean Change From Baseline MAS in the Wrist Flexors at Week 4
Cycle 2
|
-1.6 units on a scale
Standard Deviation 1.3
|
|
Mean Change From Baseline MAS in the Wrist Flexors at Week 4
Cycle 3
|
-1.6 units on a scale
Standard Deviation 1.3
|
|
Mean Change From Baseline MAS in the Wrist Flexors at Week 4
Cycle 4
|
-1.5 units on a scale
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
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 percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction in mean MAS in the wrist flexors at Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=40 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4
At least 1 Grade Reduction -Cycle 1
|
62.5 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4
At least 1 Grade Reduction -Cycle 2
|
74.3 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4
At least 1 Grade Reduction -Cycle 3
|
73.9 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4
At least 1 Grade Reduction -Cycle 4
|
50 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4
At least 2 Grades Reduction -Cycle 1
|
47.5 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4
At least 2 Grades Reduction -Cycle 2
|
54.3 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4
At least 2 Grades Reduction -Cycle 3
|
47.8 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4
At least 2 Grades Reduction -Cycle 4
|
30.0 percentage of subjects
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The clinical assessment of muscle tone was performed using the MAS. 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 mean changes from baseline to Week 4 in MAS in the elbow flexors are reported.
Outcome measures
| Measure |
Total Dysport®
n=179 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline MAS in the Elbow Flexors at Week 4
Cycle 1
|
-1.0 units on a scale
Standard Deviation 1.0
|
|
Mean Change From Baseline MAS in the Elbow Flexors at Week 4
Cycle 2
|
-1.1 units on a scale
Standard Deviation 1.1
|
|
Mean Change From Baseline MAS in the Elbow Flexors at Week 4
Cycle 3
|
-1.1 units on a scale
Standard Deviation 1.1
|
|
Mean Change From Baseline MAS in the Elbow Flexors at Week 4
Cycle 4
|
-0.8 units on a scale
Standard Deviation 1.0
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
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 percentage of subjects at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the elbow flexors at Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=69 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4
At least 1 Grade Reduction -Cycle 3
|
75.6 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4
At least 1 Grade Reduction -Cycle 1
|
84.1 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4
At least 1 Grade Reduction -Cycle 2
|
78.3 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4
At least 1 Grade Reduction -Cycle 4
|
73.3 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4
At least 2 Grades Reduction -Cycle 1
|
34.8 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4
At least 2 Grades Reduction -Cycle 2
|
41.7 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4
At least 2 Grades Reduction -Cycle 3
|
33.3 percentage of subjects
|
|
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4
At least 2 Grades Reduction -Cycle 4
|
40.0 percentage of subjects
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The clinical assessment of muscle tone was performed using the MAS. 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 mean changes from baseline to Week 4 in MAS in the shoulder extensors are reported.
Outcome measures
| Measure |
Total Dysport®
n=81 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline MAS in the Shoulder Extensors at Week 4
Cycle 1
|
-0.9 units on a scale
Standard Deviation 1.1
|
|
Mean Change From Baseline MAS in the Shoulder Extensors at Week 4
Cycle 2
|
-0.7 units on a scale
Standard Deviation 0.9
|
|
Mean Change From Baseline MAS in the Shoulder Extensors at Week 4
Cycle 3
|
-0.6 units on a scale
Standard Deviation 1.0
|
|
Mean Change From Baseline MAS in the Shoulder Extensors at Week 4
Cycle 4
|
-0.6 units on a scale
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The PGA 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. An assessment of overall treatment response was conducted by the investigator and the mean PGA scores during long-term open label treatment with Dysport were reported.
Outcome measures
| Measure |
Total Dysport®
n=253 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Physician's Global Assessment (PGA) of Treatment Response at Week 4
Cycle 1
|
1.7 units on a scale
Standard Deviation 1
|
|
Physician's Global Assessment (PGA) of Treatment Response at Week 4
Cycle 2
|
1.9 units on a scale
Standard Deviation 1
|
|
Physician's Global Assessment (PGA) of Treatment Response at Week 4
Cycle 3
|
1.9 units on a scale
Standard Deviation 1
|
|
Physician's Global Assessment (PGA) of Treatment Response at Week 4
Cycle 4
|
2 units on a scale
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
At baseline the subject and investigator together selected one of the four DAS domains as the PTT. The selected domain was required to have a rating of moderate or severe (≥2) at baseline. The DAS is a 4-point scale, the extent of functional impairment in 4 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). The mean changes in DAS at Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=252 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline in Disability Assessment Scale (DAS) Score for the Principal Target of Treatment (PTT) at Week 4
Cycle 1
|
-0.9 units on a scale
Standard Deviation 0.8
|
|
Mean Change From Baseline in Disability Assessment Scale (DAS) Score for the Principal Target of Treatment (PTT) at Week 4
Cycle 2
|
-1.1 units on a scale
Standard Deviation 0.8
|
|
Mean Change From Baseline in Disability Assessment Scale (DAS) Score for the Principal Target of Treatment (PTT) at Week 4
Cycle 3
|
-1.1 units on a scale
Standard Deviation 0.8
|
|
Mean Change From Baseline in Disability Assessment Scale (DAS) Score for the Principal Target of Treatment (PTT) at Week 4
Cycle 4
|
-1.1 units on a scale
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
At baseline the subject and investigator together selected one of the four DAS domains as the PTT. The selected domain was required to have a rating of moderate or severe (≥2) at baseline. The DAS is a 4-point scale, the extent of functional impairment in 4 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). The percentage of subjects with at least 1 grade reduction from baseline in DAS for PTT at Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=254 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Percentage of Subjects With at Least 1 Grade Reduction in DAS for PTT at Week 4
Cycle 1
|
68.5 Percentage of Subjects
|
|
Percentage of Subjects With at Least 1 Grade Reduction in DAS for PTT at Week 4
Cycle 2
|
75.1 Percentage of Subjects
|
|
Percentage of Subjects With at Least 1 Grade Reduction in DAS for PTT at Week 4
Cycle 3
|
73.7 Percentage of Subjects
|
|
Percentage of Subjects With at Least 1 Grade Reduction in DAS for PTT at Week 4
Cycle 4
|
74.1 Percentage of Subjects
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The DAS is a 4-point scale. The extent of functional impairment in 4 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). The percentage of subjects with at least one grade reduction in DAS for each of the individual domains at Week 4 is reported.
Outcome measures
| Measure |
Total Dysport®
n=254 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Hygiene - Cycle 1
|
40.9 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Hygiene - Cycle 2
|
45.4 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Dressing - Cycle 3
|
46.9 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Dressing - Cycle 4
|
53.1 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Limb Position - Cycle 2
|
59.4 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Limb Position - Cycle 3
|
60.6 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Limb Position - Cycle 4
|
53.1 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Pain - Cycle 1
|
33.1 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Pain - Cycle 2
|
36.7 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Pain - Cycle 3
|
42.3 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Pain - Cycle 4
|
48.1 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Hygiene - Cycle 3
|
44.6 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Hygiene - Cycle 4
|
46.9 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Dressing - Cycle 1
|
40.9 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Dressing - Cycle 2
|
47.2 percentage of subjects
|
|
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4
Limb Position - Cycle 1
|
55.5 percentage of subjects
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The Tardieu Scale (TS) was used to measure spasticity in extrinsic finger flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=144 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Spasticity (X) - Cycle 1
|
-33.5 Degrees
Standard Deviation 54
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Spasticity (X) - Cycle 2
|
-33.9 Degrees
Standard Deviation 55.9
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Spasticity (X) - Cycle 3
|
-43.3 Degrees
Standard Deviation 57.8
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Spasticity (X) - Cycle 4
|
-35.9 Degrees
Standard Deviation 48
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Arrest (XV1) - Cycle 1
|
24.3 Degrees
Standard Deviation 36.1
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Arrest (XV1) - Cycle 2
|
25.9 Degrees
Standard Deviation 36.5
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Arrest (XV1) - Cycle 3
|
24.9 Degrees
Standard Deviation 38.7
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Arrest (XV1) - Cycle 4
|
21.8 Degrees
Standard Deviation 39.6
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Catch (XV3) - Cycle 1
|
57.8 Degrees
Standard Deviation 55.1
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Catch (XV3) - Cycle 2
|
59.8 Degrees
Standard Deviation 57.8
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Catch (XV3) - Cycle 3
|
68.2 Degrees
Standard Deviation 55.6
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG
Angle of Catch (XV3) - Cycle 4
|
57.7 Degrees
Standard Deviation 52.6
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The TS was used to measure spasticity in extrinsic finger flexors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=144 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Extrinsic Finger Flexors as PTMG
Cycle 1
|
-0.6 units on a scale
Standard Deviation 0.7
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Extrinsic Finger Flexors as PTMG
Cycle 2
|
-0.6 units on a scale
Standard Deviation 0.8
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Extrinsic Finger Flexors as PTMG
Cycle 3
|
-0.6 units on a scale
Standard Deviation 0.8
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Extrinsic Finger Flexors as PTMG
Cycle 4
|
-0.5 units on a scale
Standard Deviation 0.7
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The TS was used to measure spasticity in elbow flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=69 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Spasticity (X) - Cycle 1
|
-26.4 Degrees
Standard Deviation 24.9
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Spasticity (X) -Cycle 2
|
-31 Degrees
Standard Deviation 27.7
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Spasticity (X) -Cycle 3
|
-33.3 Degrees
Standard Deviation 26
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Spasticity (X) -Cycle 4
|
-46.4 Degrees
Standard Deviation 17.3
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Arrest (XV1) - Cycle 1
|
-0.4 Degrees
Standard Deviation 14.9
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Arrest (XV1) - Cycle 2
|
1.3 Degrees
Standard Deviation 13.3
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of arrest (XV1) - Cycle 3
|
2.2 Degrees
Standard Deviation 10.6
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Arrest (XV1) - Cycle 4
|
-2.5 Degrees
Standard Deviation 9.4
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Catch (XV3) - Cycle 1
|
26.0 Degrees
Standard Deviation 26.1
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Catch (XV3) - Cycle 2
|
32.3 Degrees
Standard Deviation 28.8
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Catch (XV3) - Cycle 3
|
35.5 Degrees
Standard Deviation 27.3
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG
Angle of Catch (XV3) - Cycle 4
|
43.9 Degrees
Standard Deviation 23.1
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The TS was used to measure spasticity in elbow flexors.The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=69 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Elbow Flexors as PTMG
Cycle 1
|
-0.3 units on a scale
Standard Deviation 0.5
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Elbow Flexors as PTMG
Cycle 2
|
-0.4 units on a scale
Standard Deviation 0.7
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Elbow Flexors as PTMG
Cycle 3
|
-0.5 units on a scale
Standard Deviation 0.7
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Elbow Flexors as PTMG
Cycle 4
|
-0.6 units on a scale
Standard Deviation 0.5
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The TS was used to measure spasticity in wrist flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=39 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Spasticity (X) - Cycle 1
|
-23.3 Degrees
Standard Deviation 32.5
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Spasticity (X) - Cycle 2
|
-28.8 Degrees
Standard Deviation 37.1
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Spasticity (X) - Cycle 3
|
-21.7 Degrees
Standard Deviation 35.2
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Spasticity (X) - Cycle 4
|
-13.5 Degrees
Standard Deviation 29.3
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Arrest (XV1) - Cycle 1
|
12.6 Degrees
Standard Deviation 21.3
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Arrest (XV1) - Cycle 2
|
16.4 Degrees
Standard Deviation 23.9
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Arrest (XV1) - Cycle 3
|
18.6 Degrees
Standard Deviation 30.6
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Arrest (XV1) - Cycle 4
|
19.0 Degrees
Standard Deviation 24.8
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Catch (XV3) - Cycle 1
|
35.9 Degrees
Standard Deviation 35.0
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Catch (XV3) - Cycle 2
|
45.2 Degrees
Standard Deviation 37.7
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Catch (XV3) - Cycle 3
|
40.3 Degrees
Standard Deviation 33.3
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG
Angle of Catch (XV3) - Cycle 4
|
32.5 Degrees
Standard Deviation 28.1
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The TS was used to measure spasticity in wrist flexors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=39 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Wrist Flexors as PTMG
Cycle 1
|
-0.7 units on a scale
Standard Deviation 1.1
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Wrist Flexors as PTMG
Cycle 2
|
-0.9 units on a scale
Standard Deviation 1.0
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Wrist Flexors as PTMG
Cycle 3
|
-0.6 units on a scale
Standard Deviation 0.9
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Wrist Flexors as PTMG
Cycle 4
|
-0.3 units on a scale
Standard Deviation 0.7
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The TS was used to measure spasticity in shoulder extensors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=67 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Spasticity (X) - Cycle 1
|
-13.3 Degrees
Standard Deviation 24.6
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Spasticity (X) - Cycle 2
|
-10.8 Degrees
Standard Deviation 30.1
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Spasticity (X) - Cycle 3
|
-6.4 Degrees
Standard Deviation 23.5
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Spasticity (X) - Cycle 4
|
-7.2 Degrees
Standard Deviation 27.4
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Arrest (XV1) - Cycle 1
|
7.2 Degrees
Standard Deviation 16.0
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Arrest (XV1) - Cycle 2
|
6.4 Degrees
Standard Deviation 23.0
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Arrest (XV1) - Cycle 3
|
10.7 Degrees
Standard Deviation 23.8
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Arrest (XV1) - Cycle 4
|
10.8 Degrees
Standard Deviation 26.1
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Catch (XV3) - Cycle 1
|
20.5 Degrees
Standard Deviation 22.7
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Catch (XV3) - Cycle 2
|
17.2 Degrees
Standard Deviation 26.9
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Catch (XV3) - Cycle 3
|
17.1 Degrees
Standard Deviation 24.5
|
|
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors
Angle of Catch (XV3) - Cycle 4
|
18.0 Degrees
Standard Deviation 19.6
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The TS was used to measure spasticity in shoulder extensors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=67 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Shoulder Extensors
Cycle 1
|
-0.1 units on a scale
Standard Deviation 0.4
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Shoulder Extensors
Cycle 2
|
-0.1 units on a scale
Standard Deviation 0.6
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Shoulder Extensors
Cycle 3
|
-0.2 units on a scale
Standard Deviation 0.7
|
|
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Shoulder Extensors
Cycle 4
|
-0.2 units on a scale
Standard Deviation 0.5
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The AROM was assessed by the range of extension achieved by the subject moving each joint in the PTMGs (extrinsic finger flexors, elbow flexors and wrist flexors) without assistance. A goniometer was used for measurements in the elbow and wrist flexors but not for measurements in the extrinsic finger flexors. Mean changes in AROM in the 3 possible PTMGs from baseline to Week 4 are reported.
Outcome measures
| Measure |
Total Dysport®
n=144 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Extrinsic Finger Flexors: Cycle 1
|
31.3 units on a scale
Standard Deviation 40.9
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Extrinsic Finger Flexors: Cycle 2
|
34.4 units on a scale
Standard Deviation 45
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Extrinsic Finger Flexors: Cycle 3
|
33.5 units on a scale
Standard Deviation 47.1
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Extrinsic Finger Flexors: Cycle 4
|
38 units on a scale
Standard Deviation 53.4
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Elbow Flexors: Cycle 1
|
10.7 units on a scale
Standard Deviation 25.5
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Elbow Flexors: Cycle 2
|
17.6 units on a scale
Standard Deviation 23.3
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Elbow Flexors: Cycle 3
|
14.5 units on a scale
Standard Deviation 24.1
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Elbow Flexors: Cycle 4
|
13.6 units on a scale
Standard Deviation 20.6
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Wrist Flexors: Cycle 1
|
17.3 units on a scale
Standard Deviation 28.6
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Wrist Flexors: Cycle 2
|
23 units on a scale
Standard Deviation 32.7
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Wrist Flexors: Cycle 3
|
22 units on a scale
Standard Deviation 30.9
|
|
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs
Wrist Flexors: Cycle 4
|
3 units on a scale
Standard Deviation 25.1
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
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). Mean change in ease of applying a splint from baseline to Week 4 was reported.
Outcome measures
| Measure |
Total Dysport®
n=218 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline at Week 4 in Ease of Applying a Splint
Cycle 4
|
-0.4 units on a scale
Standard Deviation 1
|
|
Mean Change From Baseline at Week 4 in Ease of Applying a Splint
Cycle 1
|
-0.4 units on a scale
Standard Deviation 1.1
|
|
Mean Change From Baseline at Week 4 in Ease of Applying a Splint
Cycle 2
|
-0.4 units on a scale
Standard Deviation 1.3
|
|
Mean Change From Baseline at Week 4 in Ease of Applying a Splint
Cycle 3
|
-0.4 units on a scale
Standard Deviation 1.4
|
SECONDARY outcome
Timeframe: At Week 4Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
The MFS was used to measure upper limb active function. Each subject was video taped 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. The MFS consists of 10 tasks asking the subject to reach, grasp, carry and release different objects of different sizes which subjects are likely to use in their daily life. Each of these tasks was rated on a 10 point scale ranging from no movement to normal movement; for each task, the score 5 is used to rate a task barely accomplished. Mean change in MFS from baseline to Week 4 was reported.
Outcome measures
| Measure |
Total Dysport®
n=219 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline in Modified Frenchay Scale (MFS) at Week 4
Cycle 1
|
0.4 units on a scale
Standard Deviation 0.77
|
|
Mean Change From Baseline in Modified Frenchay Scale (MFS) at Week 4
Cycle 2
|
0.51 units on a scale
Standard Deviation 0.8
|
|
Mean Change From Baseline in Modified Frenchay Scale (MFS) at Week 4
Cycle 3
|
0.44 units on a scale
Standard Deviation 0.82
|
|
Mean Change From Baseline in Modified Frenchay Scale (MFS) at Week 4
Cycle 4
|
0.4 units on a scale
Standard Deviation 0.75
|
SECONDARY outcome
Timeframe: Up to Week 52Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
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 non-preference based health status measure. This instrument assessed subject health across 8 variable dimensions, which are specific health domains such as physical functioning, social functioning and vitality. Each variable item score is coded and turned into a 0-100 scale where 0 indicates the worst and 100 indicates the best possible health state for both the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the questionnaire. Baseline results and the change from baseline to end of study/early withdrawal for the PCS and MCS are reported.
Outcome measures
| Measure |
Total Dysport®
n=244 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) at End of Study/Early Withdrawal Visit
PCS Baseline
|
37.49 units on a scale
Standard Deviation 8.94
|
|
Mean Change From Baseline in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) at End of Study/Early Withdrawal Visit
PCS Change
|
1.07 units on a scale
Standard Deviation 6.76
|
|
Mean Change From Baseline in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) at End of Study/Early Withdrawal Visit
MCS Baseline
|
46.88 units on a scale
Standard Deviation 13.09
|
|
Mean Change From Baseline in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) at End of Study/Early Withdrawal Visit
MCS Change
|
0.96 units on a scale
Standard Deviation 11.11
|
SECONDARY outcome
Timeframe: Up to Week 52Population: The ITT population was defined as all enrolled subjects who received at least one injection of study medication in this open label extension study. Too few subjects were treated in Cycle 5 to allow direct comparisons with other cycles and are not reported. Only subjects with data available for analysis at the point of testing are reported.
Subjects were asked to complete the EQ-5D-5L QoL questionnaires prior to the study treatment at baseline and at the end of study/early withdrawal visit. The EQ-5D-5L 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 5 specific dimensions such as mobility, self-care, usual activity, pain/discomfort and anxiety/depression and scored their general health state. Each dimension has 5 levels of severity (no problems, slight problems,moderate problems, severe problems and extreme problems). In addition, a visual analogue scale (VAS) ranging from 0 to 100 was also included for the patients to summarize their overall health status, where 0 is the worst and 100 the best possible health state. The mean values for each dimension and the VAS scores at baseline and at the end of-study /early withdrawal are reported.
Outcome measures
| Measure |
Total Dysport®
n=249 Participants
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Anxiety/Depression Baseline
|
1.9 units on a scale
Standard Deviation 0.9
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Anxiety/Depression Change
|
-0.1 units on a scale
Standard Deviation 0.9
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Mobility Baseline
|
2.8 units on a scale
Standard Deviation 0.9
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Mobility Change
|
0 units on a scale
Standard Deviation 0.8
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Pain/Discomfort Baseline
|
2.1 units on a scale
Standard Deviation 1
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Pain/Discomfort Change
|
-0.2 units on a scale
Standard Deviation 0.9
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Self-Care Baseline
|
2.4 units on a scale
Standard Deviation 1
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Self-Care Change
|
0 units on a scale
Standard Deviation 0.8
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Usual Activities Baseline
|
2.8 units on a scale
Standard Deviation 1
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
Usual Activities Change
|
-0.2 units on a scale
Standard Deviation 1
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
VAS Baseline
|
63.6 units on a scale
Standard Deviation 19.7
|
|
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit
VAS Change
|
2.8 units on a scale
Standard Deviation 19
|
Adverse Events
Total Dysport®
Serious adverse events
| Measure |
Total Dysport®
n=254 participants at risk
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Vascular disorders
Haematoma
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Device malfunction
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Oedema peripheral
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Pyrexia
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Psychiatric disorders
Affect lability
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Psychiatric disorders
Affective disorder
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Psychiatric disorders
Mania
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Psychiatric disorders
Suicidal ideation
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Psychiatric disorders
Suicide attempt
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Cardiac disorders
Atrial fibrillation
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Cardiac disorders
Bradycardia
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Cardiac disorders
Myocardial infarction
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Blood and lymphatic system disorders
Nephrogenic anaemia
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Epilepsy
|
0.79%
2/254 • Number of events 2 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Brain injury
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Dizziness
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Syncope
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Gastrointestinal disorders
Constipation
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Gastrointestinal disorders
Volvulus
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Renal and urinary disorders
Urinary retention
|
0.79%
2/254 • Number of events 2 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Urinary tract infection
|
0.39%
1/254 • Number of events 1 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
Other adverse events
| Measure |
Total Dysport®
n=254 participants at risk
A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months.
All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response.
From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.
|
|---|---|
|
Vascular disorders
Hypertension
|
1.6%
4/254 • Number of events 5 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Injury, poisoning and procedural complications
Fall
|
7.9%
20/254 • Number of events 25 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Injury, poisoning and procedural complications
Hand fracture
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Injury, poisoning and procedural complications
Contusion
|
1.6%
4/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Investigations
Alanine aminotransferase increased
|
1.2%
3/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.2%
3/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
1.2%
3/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Immune system disorders
Seasonal allergy
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Headache
|
2.4%
6/254 • Number of events 6 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Epilepsy
|
1.2%
3/254 • Number of events 6 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Nervous system disorders
Paraesthesia
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Asthenia
|
2.0%
5/254 • Number of events 5 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Fatigue
|
2.8%
7/254 • Number of events 8 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Pyrexia
|
1.2%
3/254 • Number of events 5 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Peripheral swelling
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Oedema peripheral
|
1.6%
4/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
General disorders
Injection site bruising
|
1.2%
3/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Psychiatric disorders
Anxiety
|
2.0%
5/254 • Number of events 5 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Psychiatric disorders
Depression
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.5%
14/254 • Number of events 18 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.1%
13/254 • Number of events 14 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.0%
5/254 • Number of events 5 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.1%
8/254 • Number of events 9 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Bronchitis
|
2.0%
5/254 • Number of events 5 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Nasopharyngitis
|
2.4%
6/254 • Number of events 7 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Urinary tract infection
|
2.4%
6/254 • Number of events 10 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Influenza
|
1.6%
4/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Sinusitis
|
1.6%
4/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Cystitis
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Gastroenteritis viral
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Herpes zoster
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Infections and infestations
Upper respiratory tract
|
1.2%
3/254 • Number of events 3 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Gastrointestinal disorders
Constipation
|
1.2%
3/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.2%
3/254 • Number of events 4 • Up to Week 52
An AE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place