Dysport® Adult Lower Limb Spasticity Follow-on Study
Sponsor
Ipsen (Industry)
Overall Status
Completed
CT.gov ID
NCT01251367
Collaborator
(none)
352
50
1
46
7
0.2
Study Details
Study Description
Brief Summary
The purpose of this research study is to assess the long term safety of Dysport® in hemiparetic subjects with lower limb spasticity due to stroke or traumatic brain injury over repeated treatment cycles.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
352 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III, Prospective, Multicentre, Open Label, Extension Study, to Assess the Long Term Safety and Efficacy of Repeated Treatment of Dysport® Intramuscular Injection in the Treatment of Lower Limb Spasticity in Adult Subjects With Spastic Hemiparesis Due to Stroke or Traumatic Brain Injury
Study Start Date
:
Jun 1, 2011
Actual Primary Completion Date
:
Apr 1, 2015
Actual Study Completion Date
:
Apr 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dysport® Dysport® is injected into lower limbs across 4 cycles of treatment, a minimum of 12 weeks between 2 injections. Doses vary from 1000 U to 1500 U. |
Biological: Botulinum toxin type A
I.M. (intramuscular) injection on day 1 of each treatment cycle.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) [Up to EOS (maximum duration of 52 weeks).]
Adverse events (AEs) were monitored from the time that the subject gave informed consent to the end of the study/early withdrawal (EOS/EW). An AE was reported as a TEAE if it was not present prior to study treatment administration in Study 140, or if it was present prior to study treatment in Study 140 but the intensity increased during the treatment phase of this study. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any AE that was assessed as a hypersensitivity reaction. TEAEs, treatment related TEAEs, severe TEAEs, TEAEs leading to death, TEAEs leading to withdrawal, treatment emergent AESIs, and serious adverse events (SAEs) are summarised by treatment cycle.
- Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) [Baseline and Week 4 of each cycle]
Systolic and diastolic BP were recorded at baseline and at each subsequent study visit. BP was measured with the subject in a sitting position after resting for 3 minutes. Mean change in BP from baseline at Week 4 is reported per cycle.
- Mean Change From Baseline to Week 4 in Heart Rate (HR) [Baseline and Week 4 of each cycle]
HR was recorded at baseline and at each subsequent study visit. HR was measured with the subject in a sitting position after resting for 3 minutes. Mean change in HR from baseline at Week 4 is reported per cycle.
- Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count [Baseline and Week 4 of each cycle]
Blood samples for RBC count were taken at baseline, at Week 4, and at EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) [Baseline and Week 4 of each cycle]
Blood samples for haemoglobin and MCHC were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Haematocrit [Baseline and Week 4 of each cycle]
Blood samples for haematocrit were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH) [Baseline and Week 4 of each cycle]
Blood samples for MCH were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV) [Baseline and Week 4 of each cycle]
Blood samples for MCV were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets [Baseline and Week 4 of each cycle]
Blood samples for WBC count with differentials (neutrophils, lymphocytes) and platelet count were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) [Baseline and Week 4 of each cycle]
Blood samples were taken at baseline, at Week 4, and at the EOS/EW for analysis of the following clinical chemistry parameters: ALP, GGT, SGOT and SGPT. Outcome measure is reported per cycle as change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine [Baseline and Week 4 of each cycle]
Blood samples for clinical chemistry analysis of total bilirubin and creatinine were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose [Baseline and Week 4 of each cycle]
Blood samples for analysis of BUN and fasting blood glucose levels were taken at baseline, at Week 4 and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.
- Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport® [At Week 4]
Blood samples were collected at baseline, Week 4 and at EOS/EW to test for the presence of BTX-A antibodies. The number of subjects who were either NAb positive at baseline or negative at baseline but then positive following injection of Dysport® were reported.
- Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) [Baseline and Week 4 of each cycle]
12-lead ECG tracing was performed at baseline, at Week 4 of each cycle and at EOS/EW. The 12-lead ECG recordings were performed at a paper speed of 25 millimetres/second (mm/s), recorded with the subject in a supine position after 5 minutes rest. The ECG parameters; QT Duration, QT interval corrected with Fridericia's method (QTcF), QT interval corrected with Bazett's method (QTcB), QRS duration and PR duration were recorded and outcome measure is reported per cycle as change from baseline at Week 4.
Secondary Outcome Measures
- Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) [Baseline and Week 4 of each cycle]
Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM)), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. Outcome measure is reported per cycle as mean change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed) [Baseline and Week 4 of each cycle]
Muscle tone in the treated limb was assessed by MAS in the soleus muscle (with the knee flexed) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. Outcome measure is reported per cycle as mean change from baseline at Week 4.
- Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 [Week 4 of each cycle]
Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. Outcome measure is reported per cycle as the percentage of subjects with at least a 1 grade reduction or 2 grades reduction in MAS score at Week 4.
- Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 [Week 4 of each cycle]
Muscle tone in the treated limb was assessed by MAS in the soleus muscle (with the knee flexed) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. Outcome measure is reported per cycle as the percentage of subjects with at least a 1 grade reduction or 2 grades reduction in MAS score at Week 4.
- Physician's Global Assessment (PGA) of Treatment Response at Week 4 [Week 4 of each cycle]
An assessment of overall treatment response was conducted by the investigator at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a nine-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. The mean PGA scores per cycle at Week 4 were reported.
- Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4 [Week 4 of each cycle]
An assessment of overall treatment response was conducted by the investigator at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a nine 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. The percentage of responders with a PGA score of +1 or greater are reported at Week 4.
- Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended [Baseline and Week 4 of each cycle]
Range of active dorsiflexion of the ankle joint of the treated limb, measured using a goniometre, both with the knee flexed (90°) and extended, was used to assess treatment response. The measurements were obtained at the end of baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Lower Limb Pain [Baseline and Week 4 of each cycle]
The intensity of lower limb pain in the treated limb was evaluated by the subject using the Scale of Pain Intensity (SPIN) which provided a pictorial representation of pain in a 6-point graphic scale with the degree of red shading inside a circle representing the intensity of pain. The bottom and top of the scale are anchored by two extremes: 'no pain' (circle with no red shading and scored as 0) and 'pain as bad as it could be' (circle completely red and scored as 5), marked with either verbal or visual cues. The intervening points are represented by red circles increasing proportionally in size. The subject marks the circle that best indicates their pain intensity. The SPIN assessments were obtained at baseline, Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at the EOS/EW. The mean changes from baseline in subjects with a baseline SPIN Score >0 at Week 4 was reported per cycle.
- Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) [Baseline and Week 4 of each cycle]
Subjects were asked to complete the SF-36 health surveys prior to the study treatment at baseline, at Week 4 and at the EOS/EW 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. The mean change in the PCS and MCS from baseline to Week 4 are reported.
- Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL [Baseline and Week 4 of each cycle]
Subjects were asked to complete the EQ-5D-5L QoL questionnaire prior to the study treatment at baseline, at Week 4 and at EOS/EW 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, rated from 1 to 5 (best to worst). 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 change in pain and discomfort and VAS scores from baseline to Week 4 are reported.
- Mean Change From Baseline to Week 4 in Walking Speed (WS) [Baseline and Week 4 of each cycle]
All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of WS were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Step Length [Baseline and Week 4 of each cycle]
All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of step length were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Cadence [Baseline and Week 4 of each cycle]
All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of cadence were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4.
- Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) [Baseline and Week 4 of each cycle]
Spasticity in the treated limb was assessed using the Tardieu Scale (TS) for the GSC (knee extended). 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 at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. 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 per cycle.
- Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended) [Baseline and Week 4 of each cycle]
Spasticity in the treated limb was assessed using the TS for the GSC (knee extended). 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. Spasticity grade (Y) was recorded at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported per cycle.
- Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) [Baseline and Week 4 of each cycle]
Spasticity in the treated limb was assessed using the TS for the soleus muscle (knee flexed). 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 at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. 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 per cycle.
- Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed) [Baseline and Week 4 of each cycle]
Spasticity in the treated limb was assessed using the TS for the soleus muscle (knee flexed). 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. Spasticity grade (Y) was recorded at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported per cycle.
- Use of Walking Aids/Orthoses at Baseline and Week 4 [Baseline and Week 4 of each cycle]
Subjects were assessed on their use of walking aids and orthoses at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at the EOS/EW visit. Outcome measure is reported per cycle at baseline and Week 4. Number of subjects with no walking aid/orthoses were included in the 'No Walking Aid' category and number of subjects with any kind of walking aid/orthosis (including single point cane, tripod cane, ankle foot orthosis or other type of walking aid/orthosis) were combined into the 'Walking Aid' category.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Completion of Dysport® Adult Lower Limb Spasticity Double Blind study Y-55-52120-140 (NCT01249404)
Exclusion Criteria:
- Fixed contractures in lower limb
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Arizona | Scottsdale | Arizona | United States | 85259 |
| 2 | Rancho Los Amigos | Downey | California | United States | 90242 |
| 3 | Pacific Neuroscience Medical Group | Oxnard | California | United States | 93030 |
| 4 | Associated Neurologist of Southern CT, PC | Fairfield | Connecticut | United States | 06824 |
| 5 | Design Neuroscience Center | Miami | Florida | United States | 33136 |
| 6 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 7 | Island Neurological Associates | Plainview | New York | United States | 11803 |
| 8 | University of North Carolina - Chapel Hill | Chapel Hill | North Carolina | United States | 27599-7200 |
| 9 | Wake Forest University Baptist Medical Center | Winston-Salem | North Carolina | United States | 27157 |
| 10 | Moss Rehab & Albert Einstein | Elkins Park | Pennsylvania | United States | 19027 |
| 11 | Vanderbilt University | Nashville | Tennessee | United States | 37232 |
| 12 | The University of Texas Southwestern Medical Center at Dalla | Dallas | Texas | United States | 75390-9016 |
| 13 | University of North Texas HSC at Ben Hogan Center | Fort Worth | Texas | United States | 76104 |
| 14 | University of Texas - Houston | Houston | Texas | United States | 77030 |
| 15 | University of Utah School of Medicine | Salt Lake City | Utah | United States | 84132 |
| 16 | St George Hospital | Kogarah | Australia | ||
| 17 | Epworth Rehabilitation | Melbourne | Australia | ||
| 18 | Royal Melbourne Hospital | Melbourne | Australia | ||
| 19 | St Vincent's Hospital | Melbourne | Australia | ||
| 20 | St Vincent's Hospital | Sydney | Australia | ||
| 21 | Westmead Hospital | Sydney | Australia | ||
| 22 | Université catholique de Louvain av Hippocrate 10 | Bruxelles | Belgium | ||
| 23 | Clinique Universitaire | Yvoir | Belgium | ||
| 24 | Charles University in Prague | Praha 2 | Czechia | ||
| 25 | CHU Jean MINJOZ | Besançon | France | ||
| 26 | Centre de Réadaptation de Coubert | Coubert | France | ||
| 27 | Centre Hospitalier Albert Chenevier-Hopital Henri Mondor | Créteil | France | ||
| 28 | Hopital Raymond Poincarré | Garches | France | ||
| 29 | Hôpital de L'Archet I | Nice | France | ||
| 30 | Hôpital Sébastopol | Reims | France | ||
| 31 | Hôpital Civil | Strasbourg | France | ||
| 32 | Hopital Rangueil | Toulouse | France | ||
| 33 | National Institute for Medical Rehabilitation | Budapest | Hungary | ||
| 34 | Uno Medical Trials | Budapest | Hungary | ||
| 35 | Petz Aladar Country Hospital | Gyor | Hungary | ||
| 36 | Azienda Ospedaliero Universitaria "Policlinico Vittorio Emanuele" | Catania | Italy | ||
| 37 | Specjalistyczna Praktyka Lekarska | Katowice | Poland | ||
| 38 | Centrum Medyczne Plejady | Krakow | Poland | ||
| 39 | Krakowska Akademia Neurologii Sp. z o.o. | Krakow | Poland | ||
| 40 | Malopolskie Centrum Medyczne | Krakow | Poland | ||
| 41 | Nzoz Neuro - Card | Poznan | Poland | ||
| 42 | Samodzielny Publiczny Centralny Szpital Kliniczny | Warszawa | Poland | ||
| 43 | Serviço de Reabilitação | Alcabideche | Portugal | ||
| 44 | Centro Hospitalar Lisboa Norte | Lisbon | Portugal | ||
| 45 | Centro Hospitalar São João | Porto | Portugal | ||
| 46 | Medical Rehabilitation Center | Moscow | Russian Federation | ||
| 47 | Scientific Research Institute of Neurology | Moscow | Russian Federation | ||
| 48 | State University | St Petersburg | Russian Federation | ||
| 49 | Derer's Hospital | Bratislava | Slovakia | ||
| 50 | Univerzitna nemocnica Bratislava | Bratislava | Slovakia |
Sponsors and Collaborators
- Ipsen
Investigators
- Study Director: Ipsen Study Director, Ipsen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Ipsen
ClinicalTrials.gov Identifier:
NCT01251367
Other Study ID Numbers:
- Y-55-52120-142
- 2009-017723-26
First Posted:
Dec 1, 2010
Last Update Posted:
Nov 22, 2019
Last Verified:
Nov 1, 2019
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was designed as a multicentre study and included 51 sites in Australia, Belgium, the Czech Republic, France, Hungary, Italy, Poland, Portugal, Russia, Slovakia and the United States of America that included at least one subject. The current study (Study 142) was an open label extension to the double blind Study 140 (Y-55-52120-140). |
|---|---|
| Pre-assignment Detail | A total of 366 subjects completed Study 140, of which 352 subjects were enrolled in Study 142. Of these, 7 subjects entered an observational phase and never received open label treatment with Dysport® in Study 142 and the remaining 345 subjects started treatment and received at least one open label injection of Dysport® in Study 142. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 Units [U] or 1000 U) by intramuscular (i.m.) injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Period Title: Overall Study | |
| STARTED | 345 |
| Cycle 1 | 345 |
| Cycle 2 | 297 |
| Cycle 3 | 224 |
| Cycle 4 | 139 |
| COMPLETED | 269 |
| NOT COMPLETED | 76 |
Baseline Characteristics
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Overall Participants | 345 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
280
81.2%
|
| >=65 years |
65
18.8%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
53.1
(12.8)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
110
31.9%
|
| Male |
235
68.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
34
9.9%
|
| Not Hispanic or Latino |
311
90.1%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
7
2%
|
| Native Hawaiian or Other Pacific Islander |
1
0.3%
|
| Black or African American |
21
6.1%
|
| White |
313
90.7%
|
| More than one race |
3
0.9%
|
| Unknown or Not Reported |
0
0%
|
Outcome Measures
| Title | Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs) |
|---|---|
| Description | Adverse events (AEs) were monitored from the time that the subject gave informed consent to the end of the study/early withdrawal (EOS/EW). An AE was reported as a TEAE if it was not present prior to study treatment administration in Study 140, or if it was present prior to study treatment in Study 140 but the intensity increased during the treatment phase of this study. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any AE that was assessed as a hypersensitivity reaction. TEAEs, treatment related TEAEs, severe TEAEs, TEAEs leading to death, TEAEs leading to withdrawal, treatment emergent AESIs, and serious adverse events (SAEs) are summarised by treatment cycle. |
| Time Frame | Up to EOS (maximum duration of 52 weeks). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| TEAE - Cycle 1 |
140
40.6%
|
| TEAE - Cycle 2 |
97
28.1%
|
| TEAE - Cycle 3 |
47
13.6%
|
| TEAE - Cycle 4 |
21
6.1%
|
| Treatment Related TEAE - Cycle 1 |
43
12.5%
|
| Treatment Related TEAE - Cycle 2 |
23
6.7%
|
| Treatment Related TEAE - Cycle 3 |
7
2%
|
| Treatment Related TEAE - Cycle 4 |
5
1.4%
|
| Severe TEAE - Cycle 1 |
13
3.8%
|
| Severe TEAE - Cycle 2 |
9
2.6%
|
| Severe TEAE - Cycle 3 |
4
1.2%
|
| Severe TEAE - Cycle 4 |
2
0.6%
|
| TEAE leading to death - Cycle 1 |
0
0%
|
| TEAE leading to death - Cycle 2 |
1
0.3%
|
| TEAE leading to death - Cycle 3 |
1
0.3%
|
| TEAE leading to death - Cycle 4 |
0
0%
|
| TEAE leading to withdrawal - Cycle 1 |
8
2.3%
|
| TEAE leading to withdrawal - Cycle 2 |
10
2.9%
|
| TEAE leading to withdrawal - Cycle 3 |
1
0.3%
|
| TEAE leading to withdrawal - Cycle 4 |
0
0%
|
| AESI - Cycle 1 |
31
9%
|
| AESI - Cycle 2 |
24
7%
|
| AESI - Cycle 3 |
10
2.9%
|
| AESI - Cycle 4 |
5
1.4%
|
| SAE - Cycle 1 |
23
6.7%
|
| SAE - Cycle 2 |
14
4.1%
|
| SAE - Cycle 3 |
7
2%
|
| SAE - Cycle 4 |
2
0.6%
|
| Title | Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP) |
|---|---|
| Description | Systolic and diastolic BP were recorded at baseline and at each subsequent study visit. BP was measured with the subject in a sitting position after resting for 3 minutes. Mean change in BP from baseline at Week 4 is reported per cycle. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Systolic BP - Cycle 1 |
-0.7
|
| Systolic BP - Cycle 2 |
-1.9
|
| Systolic BP - Cycle 3 |
-2.4
|
| Systolic BP - Cycle 4 |
-5.1
|
| Diastolic BP - Cycle 1 |
0.3
|
| Diastolic BP - Cycle 2 |
-0.2
|
| Diastolic BP - Cycle 3 |
-0.3
|
| Diastolic BP - Cycle 4 |
-1.1
|
| Title | Mean Change From Baseline to Week 4 in Heart Rate (HR) |
|---|---|
| Description | HR was recorded at baseline and at each subsequent study visit. HR was measured with the subject in a sitting position after resting for 3 minutes. Mean change in HR from baseline at Week 4 is reported per cycle. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
3.7
|
| Cycle 2 |
4.9
|
| Cycle 3 |
3.9
|
| Cycle 4 |
4.5
|
| Title | Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count |
|---|---|
| Description | Blood samples for RBC count were taken at baseline, at Week 4, and at EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
0.049
|
| Cycle 2 |
0.074
|
| Cycle 3 |
0.046
|
| Cycle 4 |
0.028
|
| Title | Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC) |
|---|---|
| Description | Blood samples for haemoglobin and MCHC were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Haemoglobin - Cycle 1 |
1.2
|
| Haemoglobin - Cycle 2 |
1.5
|
| Haemoglobin - Cycle 3 |
1.5
|
| Haemoglobin - Cycle 4 |
1.2
|
| MCHC - Cycle 1 |
1.9
|
| MCHC - Cycle 2 |
1.3
|
| MCHC - Cycle 3 |
3.4
|
| MCHC - Cycle 4 |
8.9
|
| Title | Mean Change From Baseline to Week 4 in Haematocrit |
|---|---|
| Description | Blood samples for haematocrit were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
0.001
|
| Cycle 2 |
0.003
|
| Cycle 3 |
-0.001
|
| Cycle 4 |
-0.009
|
| Title | Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH) |
|---|---|
| Description | Blood samples for MCH were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
-0.06
|
| Cycle 2 |
-0.17
|
| Cycle 3 |
0.00
|
| Cycle 4 |
0.05
|
| Title | Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV) |
|---|---|
| Description | Blood samples for MCV were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
-0.74
|
| Cycle 2 |
-0.9
|
| Cycle 3 |
-1.02
|
| Cycle 4 |
-2.44
|
| Title | Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets |
|---|---|
| Description | Blood samples for WBC count with differentials (neutrophils, lymphocytes) and platelet count were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| WBC count - Cycle 1 |
-0.21
|
| WBC count - Cycle 2 |
-0.32
|
| WBC count - Cycle 3 |
-0.26
|
| WBC count - Cycle 4 |
-0.02
|
| Neutrophils - Cycle 1 |
-0.17
|
| Neutrophils - Cycle 2 |
-0.27
|
| Neutrophils - Cycle 3 |
-0.28
|
| Neutrophils - Cycle 4 |
-0.06
|
| Lymphocytes - Cycle 1 |
-0.05
|
| Lymphocytes - Cycle 2 |
-0.05
|
| Lymphocytes - Cycle 3 |
0.03
|
| Lymphocytes - Cycle 4 |
-0.01
|
| Platelets - Cycle 1 |
-0.1
|
| Platelets - Cycle 2 |
0.0
|
| Platelets - Cycle 3 |
0.1
|
| Platelets - Cycle 4 |
4.6
|
| Title | Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) |
|---|---|
| Description | Blood samples were taken at baseline, at Week 4, and at the EOS/EW for analysis of the following clinical chemistry parameters: ALP, GGT, SGOT and SGPT. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| ALP - Cycle 1 |
-1.2
|
| ALP - Cycle 2 |
-2.9
|
| ALP - Cycle 3 |
-5.2
|
| ALP - Cycle 4 |
-3.2
|
| SGOT - Cycle 1 |
2.7
|
| SGOT - Cycle 2 |
3
|
| SGOT - Cycle 3 |
1.3
|
| SGOT - Cycle 4 |
1.8
|
| SGPT - Cycle 1 |
1.2
|
| SGPT - Cycle 2 |
2.4
|
| SGPT - Cycle 3 |
1.7
|
| SGPT - Cycle 4 |
0.8
|
| GGT - Cycle 1 |
1
|
| GGT - Cycle 2 |
-1.9
|
| GGT - Cycle 3 |
-3
|
| GGT - Cycle 4 |
-0.4
|
| Title | Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine |
|---|---|
| Description | Blood samples for clinical chemistry analysis of total bilirubin and creatinine were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Total bilirubin - Cycle 1 |
0.13
|
| Total bilirubin - Cycle 2 |
0.14
|
| Total bilirubin - Cycle 3 |
0.03
|
| Total bilirubin - Cycle 4 |
-0.05
|
| Creatinine - Cycle 1 |
-2
|
| Creatinine - Cycle 2 |
-5.3
|
| Creatinine - Cycle 3 |
-7.9
|
| Creatinine - Cycle 4 |
-14.2
|
| Title | Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose |
|---|---|
| Description | Blood samples for analysis of BUN and fasting blood glucose levels were taken at baseline, at Week 4 and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| BUN - Cycle 1 |
0.14
|
| BUN - Cycle 2 |
-0.05
|
| BUN - Cycle 3 |
-0.19
|
| BUN - Cycle 4 |
-0.37
|
| Fasting blood glucose - Cycle 1 |
-0.046
|
| Fasting blood glucose - Cycle 2 |
0.009
|
| Fasting blood glucose - Cycle 3 |
0.015
|
| Fasting blood glucose - Cycle 4 |
0.231
|
| Title | Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport® |
|---|---|
| Description | Blood samples were collected at baseline, Week 4 and at EOS/EW to test for the presence of BTX-A antibodies. The number of subjects who were either NAb positive at baseline or negative at baseline but then positive following injection of Dysport® were reported. |
| Time Frame | At Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. In addition, the antibody analysis included subjects who had an antibody assessment at baseline and at a post baseline visit (n=343). |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Positive at baseline |
3
0.9%
|
| Negative at baseline & positive post baseline |
0
0%
|
| Title | Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG) |
|---|---|
| Description | 12-lead ECG tracing was performed at baseline, at Week 4 of each cycle and at EOS/EW. The 12-lead ECG recordings were performed at a paper speed of 25 millimetres/second (mm/s), recorded with the subject in a supine position after 5 minutes rest. The ECG parameters; QT Duration, QT interval corrected with Fridericia's method (QTcF), QT interval corrected with Bazett's method (QTcB), QRS duration and PR duration were recorded and outcome measure is reported per cycle as change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 324 |
| QT Duration - Cycle 1 |
-10.1
(24.9)
|
| QT Duration - Cycle 2 |
-12.2
(22.9)
|
| QT Duration - Cycle 3 |
-13.6
(26.5)
|
| QT Duration - Cycle 4 |
-16.5
(23.5)
|
| QTcF - Cycle 1 |
-0.6
(16.9)
|
| QTcF - Cycle 2 |
-1.9
(14.8)
|
| QTcF - Cycle 3 |
-3.8
(16.2)
|
| QTcF - Cycle 4 |
-1.8
(16.1)
|
| QTcB - Cycle 1 |
4.5
(20.2)
|
| QTcB - Cycle 2 |
3.5
(18.4)
|
| QTcB - Cycle 3 |
1.5
(19.5)
|
| QTcB - Cycle 4 |
6.1
(21.3)
|
| QRS Duration - Cycle 1 |
-0.6
(6.3)
|
| QRS Duration - Cycle 2 |
-0.7
(5.8)
|
| QRS Duration - Cycle 3 |
-0.8
(6.2)
|
| QRS Duration - Cycle 4 |
-0.9
(6.7)
|
| PR Duration - Cycle 1 |
-2.2
(14.5)
|
| PR Duration - Cycle 2 |
-1.7
(15.2)
|
| PR Duration - Cycle 3 |
-0.5
(14.4)
|
| PR Duration - Cycle 4 |
-0.6
(13.4)
|
| Title | Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) |
|---|---|
| Description | Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM)), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. Outcome measure is reported per cycle as mean change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
-0.8
(0.9)
|
| Cycle 2 |
-0.9
(1)
|
| Cycle 3 |
-1
(1)
|
| Cycle 4 |
-1
(0.9)
|
| Title | Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed) |
|---|---|
| Description | Muscle tone in the treated limb was assessed by MAS in the soleus muscle (with the knee flexed) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. Outcome measure is reported per cycle as mean change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
-1
(1.2)
|
| Cycle 2 |
-1.1
(1)
|
| Cycle 3 |
-1.2
(1)
|
| Cycle 4 |
-1.1
(1.1)
|
| Title | Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4 |
|---|---|
| Description | Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. Outcome measure is reported per cycle as the percentage of subjects with at least a 1 grade reduction or 2 grades reduction in MAS score at Week 4. |
| Time Frame | Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| At least 1 grade reduction - Cycle 1 |
56.2
16.3%
|
| At least 1 grade reduction - Cycle 2 |
57.6
16.7%
|
| At least 1 grade reduction - Cycle 3 |
60.7
17.6%
|
| At least 1 grade reduction - Cycle 4 |
66.9
19.4%
|
| At least 2 grades reduction - Cycle 1 |
18.3
5.3%
|
| At least 2 grades reduction - Cycle 2 |
23.2
6.7%
|
| At least 2 grades reduction - Cycle 3 |
23.2
6.7%
|
| At least 2 grades reduction - Cycle 4 |
22.3
6.5%
|
| Title | Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4 |
|---|---|
| Description | Muscle tone in the treated limb was assessed by MAS in the soleus muscle (with the knee flexed) at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. Outcome measure is reported per cycle as the percentage of subjects with at least a 1 grade reduction or 2 grades reduction in MAS score at Week 4. |
| Time Frame | Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| At least 1 grade reduction - Cycle 1 |
61.4
17.8%
|
| At least 1 grade reduction - Cycle 2 |
68.4
19.8%
|
| At least 1 grade reduction - Cycle 3 |
72.3
21%
|
| At least 1 grade reduction - Cycle 4 |
71.9
20.8%
|
| At least 2 grades reduction - Cycle 1 |
28.4
8.2%
|
| At least 2 grades reduction - Cycle 2 |
30.6
8.9%
|
| At least 2 grades reduction - Cycle 3 |
30.4
8.8%
|
| At least 2 grades reduction - Cycle 4 |
28.8
8.3%
|
| Title | Physician's Global Assessment (PGA) of Treatment Response at Week 4 |
|---|---|
| Description | An assessment of overall treatment response was conducted by the investigator at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a nine-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. The mean PGA scores per cycle at Week 4 were reported. |
| Time Frame | Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
1.4
(1.1)
|
| Cycle 2 |
1.6
(1)
|
| Cycle 3 |
1.8
(1)
|
| Cycle 4 |
1.9
(1)
|
| Title | Percentage of Subjects With a Score of at Least +1 on the PGA Scale at Week 4 |
|---|---|
| Description | An assessment of overall treatment response was conducted by the investigator at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a nine 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. The percentage of responders with a PGA score of +1 or greater are reported at Week 4. |
| Time Frame | Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
83.8
24.3%
|
| Cycle 2 |
86.2
25%
|
| Cycle 3 |
89.3
25.9%
|
| Cycle 4 |
89.9
26.1%
|
| Title | Mean Change From Baseline to Week 4 in the Range of Active Ankle Dorsiflexion Both With the Knee Flexed and With the Knee Extended |
|---|---|
| Description | Range of active dorsiflexion of the ankle joint of the treated limb, measured using a goniometre, both with the knee flexed (90°) and extended, was used to assess treatment response. The measurements were obtained at the end of baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Knee Extended - Cycle 1 |
4.1
(10.6)
|
| Knee Extended - Cycle 2 |
4.4
(10.6)
|
| Knee Extended - Cycle 3 |
6
(11.4)
|
| Knee Extended - Cycle 4 |
6.5
(10.9)
|
| Knee Flexed - Cycle 1 |
4.1
(10.7)
|
| Knee Flexed - Cycle 2 |
5
(10.3)
|
| Knee Flexed - Cycle 3 |
5.2
(10.9)
|
| Knee Flexed - Cycle 4 |
3.8
(9.8)
|
| Title | Mean Change From Baseline to Week 4 in Lower Limb Pain |
|---|---|
| Description | The intensity of lower limb pain in the treated limb was evaluated by the subject using the Scale of Pain Intensity (SPIN) which provided a pictorial representation of pain in a 6-point graphic scale with the degree of red shading inside a circle representing the intensity of pain. The bottom and top of the scale are anchored by two extremes: 'no pain' (circle with no red shading and scored as 0) and 'pain as bad as it could be' (circle completely red and scored as 5), marked with either verbal or visual cues. The intervening points are represented by red circles increasing proportionally in size. The subject marks the circle that best indicates their pain intensity. The SPIN assessments were obtained at baseline, Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at the EOS/EW. The mean changes from baseline in subjects with a baseline SPIN Score >0 at Week 4 was reported per cycle. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
-0.7
(1.2)
|
| Cycle 2 |
-0.8
(1.2)
|
| Cycle 3 |
-0.9
(1.2)
|
| Cycle 4 |
-0.9
(1.2)
|
| Title | Mean Change From Baseline to Week 4 in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) |
|---|---|
| Description | Subjects were asked to complete the SF-36 health surveys prior to the study treatment at baseline, at Week 4 and at the EOS/EW 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. The mean change in the PCS and MCS from baseline to Week 4 are reported. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| PCS - Cycle 1 |
1.05
(7.5)
|
| PCS - Cycle 2 |
1.43
(7.67)
|
| PCS - Cycle 3 |
1.85
(7.01)
|
| PCS - Cycle 4 |
2.8
(6.65)
|
| MCS - Cycle 1 |
-1.13
(11.27)
|
| MCS - Cycle 2 |
-0.82
(12.7)
|
| MCS - Cycle 3 |
0.56
(12.24)
|
| MCS - Cycle 4 |
0.14
(13.23)
|
| Title | Mean Change From Baseline in European Quality of Life - 5 Dimensions, 5 Level (EQ-5D-5L) QoL |
|---|---|
| Description | Subjects were asked to complete the EQ-5D-5L QoL questionnaire prior to the study treatment at baseline, at Week 4 and at EOS/EW 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, rated from 1 to 5 (best to worst). 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 change in pain and discomfort and VAS scores from baseline to Week 4 are reported. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Pain/discomfort - Cycle 1 |
-0.1
(1.0)
|
| Pain/discomfort - Cycle 2 |
-0.2
(1.0)
|
| Pain/discomfort - Cycle 3 |
-0.2
(1.0)
|
| Pain/discomfort - Cycle 4 |
-0.4
(1.2)
|
| VAS - Cycle 1 |
2.8
(18.3)
|
| VAS - Cycle 2 |
3.8
(17.7)
|
| VAS - Cycle 3 |
4.4
(19.9)
|
| VAS - Cycle 4 |
5.5
(21.0)
|
| Title | Mean Change From Baseline to Week 4 in Walking Speed (WS) |
|---|---|
| Description | All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of WS were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Comfortable WS, barefoot - Cycle 1 |
0.07
(0.12)
|
| Comfortable WS, barefoot - Cycle 2 |
0.08
(0.13)
|
| Comfortable WS, barefoot - Cycle 3 |
0.08
(0.13)
|
| Comfortable WS, barefoot - Cycle 4 |
0.09
(0.14)
|
| Comfortable WS, with shoes - Cycle 1 |
0.06
(0.13)
|
| Comfortable WS, with shoes - Cycle 2 |
0.07
(0.14)
|
| Comfortable WS, with shoes - Cycle 3 |
0.08
(0.13)
|
| Comfortable WS, with shoes - Cycle 4 |
0.08
(0.14)
|
| Maximal WS, barefoot - Cycle 1 |
0.07
(0.16)
|
| Maximal WS, barefoot - Cycle 2 |
0.08
(0.18)
|
| Maximal WS, barefoot - Cycle 3 |
0.09
(0.18)
|
| Maximal WS, barefoot - Cycle 4 |
0.1
(0.18)
|
| Maximal WS, with shoes - Cycle 1 |
0.07
(0.17)
|
| Maximal WS, with shoes - Cycle 2 |
0.09
(0.19)
|
| Maximal WS, with shoes - Cycle 3 |
0.09
(0.19)
|
| Maximal WS, with shoes - Cycle 4 |
0.1
(0.21)
|
| Title | Mean Change From Baseline to Week 4 in Step Length |
|---|---|
| Description | All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of step length were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Comfortable WS, barefoot - Cycle 1 |
0.03
(0.06)
|
| Comfortable WS, barefoot - Cycle 2 |
0.03
(0.09)
|
| Comfortable WS, barefoot - Cycle 3 |
0.03
(0.08)
|
| Comfortable WS, barefoot - Cycle 4 |
0.05
(0.09)
|
| Comfortable WS, with shoes - Cycle 1 |
0.03
(0.07)
|
| Comfortable WS, with shoes - Cycle 2 |
0.03
(0.08)
|
| Comfortable WS, with shoes - Cycle 3 |
0.03
(0.08)
|
| Comfortable WS, with shoes - Cycle 4 |
0.04
(0.09)
|
| Maximal WS, barefoot - Cycle 1 |
0.03
(0.08)
|
| Maximal WS, barefoot - Cycle 2 |
0.03
(0.09)
|
| Maximal WS, barefoot - Cycle 3 |
0.03
(0.09)
|
| Maximal WS, barefoot - Cycle 4 |
0.04
(0.09)
|
| Maximal WS, with shoes - Cycle 1 |
0.02
(0.08)
|
| Maximal WS, with shoes - Cycle 2 |
0.03
(0.09)
|
| Maximal WS, with shoes - Cycle 3 |
0.03
(0.09)
|
| Maximal WS, with shoes - Cycle 4 |
0.04
(0.1)
|
| Title | Mean Change From Baseline to Week 4 in Cadence |
|---|---|
| Description | All WS tests were conducted without walking aids over a distance of 10 metres at both a comfortable WS and at maximal WS. Evaluations of cadence were made barefoot and with shoes on, at baseline, at Weeks 4 and 12, at discretionary visits at Weeks 16, 20 and 24 of each cycle, and at EOS/EW. Outcome measure is reported per cycle as mean change from baseline at Week 4. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Comfortable WS, barefoot - Cycle 1 |
0.08
(0.21)
|
| Comfortable WS, barefoot - Cycle 2 |
0.08
(0.23)
|
| Comfortable WS, barefoot - Cycle 3 |
0.08
(0.21)
|
| Comfortable WS, barefoot - Cycle 4 |
0.07
(0.21)
|
| Comfortable WS, with shoes - Cycle 1 |
0.07
(0.21)
|
| Comfortable WS, with shoes - Cycle 2 |
0.08
(0.22)
|
| Comfortable WS, with shoes - Cycle 3 |
0.08
(0.22)
|
| Comfortable WS, with shoes - Cycle 4 |
0.07
(0.21)
|
| Maximal WS, barefoot - Cycle 1 |
0.07
(0.26)
|
| Maximal WS, barefoot - Cycle 2 |
0.08
(0.28)
|
| Maximal WS, barefoot - Cycle 3 |
0.09
(0.26)
|
| Maximal WS, barefoot - Cycle 4 |
0.11
(0.25)
|
| Maximal WS, with shoes - Cycle 1 |
0.07
(0.23)
|
| Maximal WS, with shoes - Cycle 2 |
0.09
(0.27)
|
| Maximal WS, with shoes - Cycle 3 |
0.09
(0.27)
|
| Maximal WS, with shoes - Cycle 4 |
0.09
(0.27)
|
| Title | Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the GSC (Knee Extended) |
|---|---|
| Description | Spasticity in the treated limb was assessed using the Tardieu Scale (TS) for the GSC (knee extended). 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 at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. 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 per cycle. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Angle of arrest (XV1) - Cycle 1 |
2.7
(7.9)
|
| Angle of arrest (XV1) - Cycle 2 |
2.4
(7.8)
|
| Angle of arrest (XV1) - Cycle 3 |
2.6
(8.9)
|
| Angle of arrest (XV1) - Cycle 4 |
2.7
(8.4)
|
| Angle of catch (XV3) - Cycle 1 |
7.1
(10.6)
|
| Angle of catch (XV3) - Cycle 2 |
7.3
(11.1)
|
| Angle of catch (XV3) - Cycle 3 |
7.9
(12.2)
|
| Angle of catch (XV3) - Cycle 4 |
9.5
(12.4)
|
| Spasticity angle (X) - Cycle 1 |
-4.4
(8.6)
|
| Spasticity angle (X) - Cycle 2 |
-4.9
(9.2)
|
| Spasticity angle (X) - Cycle 3 |
-5.4
(9.3)
|
| Spasticity angle (X) - Cycle 4 |
-6.8
(9.2)
|
| Title | Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the GSC (Knee Extended) |
|---|---|
| Description | Spasticity in the treated limb was assessed using the TS for the GSC (knee extended). 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. Spasticity grade (Y) was recorded at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported per cycle. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
-0.5
(0.8)
|
| Cycle 2 |
-0.5
(0.7)
|
| Cycle 3 |
-0.5
(0.7)
|
| Cycle 4 |
-0.5
(0.8)
|
| Title | Mean Change From Baseline to Week 4 in Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) in the Soleus Muscle (Knee Flexed) |
|---|---|
| Description | Spasticity in the treated limb was assessed using the TS for the soleus muscle (knee flexed). 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 at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. 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 per cycle. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Angle of arrest (XV1) - Cycle 1 |
1.9
(8.0)
|
| Angle of arrest (XV1) - Cycle 2 |
2.8
(8.1)
|
| Angle of arrest (XV1) - Cycle 3 |
2.6
(8.5)
|
| Angle of arrest (XV1) - Cycle 4 |
2.4
(8.6)
|
| Angle of catch (XV3) - Cycle 1 |
6.9
(10.3)
|
| Angle of catch (XV3) - Cycle 2 |
7.5
(10.8)
|
| Angle of catch (XV3) - Cycle 3 |
7.8
(11.2)
|
| Angle of catch (XV3) - Cycle 4 |
8.8
(11.4)
|
| Spasticity angle (X) - Cycle 1 |
-5.0
(10.0)
|
| Spasticity angle (X) - Cycle 2 |
-4.7
(9.8)
|
| Spasticity angle (X) - Cycle 3 |
-5.2
(9.6)
|
| Spasticity angle (X) - Cycle 4 |
-6.4
(11.1)
|
| Title | Mean Change From Baseline to Week 4 in Spasticity Grade (Y) in the Soleus Muscle (Knee Flexed) |
|---|---|
| Description | Spasticity in the treated limb was assessed using the TS for the soleus muscle (knee flexed). 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. Spasticity grade (Y) was recorded at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at EOS/EW. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported per cycle. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| Cycle 1 |
-0.6
(0.8)
|
| Cycle 2 |
-0.6
(0.7)
|
| Cycle 3 |
-0.7
(0.8)
|
| Cycle 4 |
-0.7
(0.7)
|
| Title | Use of Walking Aids/Orthoses at Baseline and Week 4 |
|---|---|
| Description | Subjects were assessed on their use of walking aids and orthoses at baseline, at Weeks 4 and 12 after each Dysport® injection, at discretionary visits at Weeks 16, 20 and 24 of each cycle and at the EOS/EW visit. Outcome measure is reported per cycle at baseline and Week 4. Number of subjects with no walking aid/orthoses were included in the 'No Walking Aid' category and number of subjects with any kind of walking aid/orthosis (including single point cane, tripod cane, ankle foot orthosis or other type of walking aid/orthosis) were combined into the 'Walking Aid' category. |
| Time Frame | Baseline and Week 4 of each cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects who received at least one open label injection of Dysport® were included in this analysis population. The number of subjects with data available for analysis at each treatment cycle are reported. |
| Arm/Group Title | Total Dysport® |
|---|---|
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). |
| Measure Participants | 345 |
| No Walking Aid at Baseline - Cycle 1 |
101
29.3%
|
| Walking Aid at Baseline - Cycle 1 |
244
70.7%
|
| No Walking Aid at Week 4 - Cycle 1 |
99
28.7%
|
| Walking Aid at Week 4 - Cycle 1 |
242
70.1%
|
| No Walking Aid at Baseline - Cycle 2 |
84
24.3%
|
| Walking Aid at Baseline - Cycle 2 |
213
61.7%
|
| No Walking Aid at Week 4 - Cycle 2 |
80
23.2%
|
| Walking Aid at Week 4 - Cycle 2 |
212
61.4%
|
| No Walking Aid at Baseline - Cycle 3 |
56
16.2%
|
| Walking Aid at Baseline - Cycle 3 |
168
48.7%
|
| No Walking Aid at Week 4 - Cycle 3 |
59
17.1%
|
| Walking Aid at Week 4 - Cycle 3 |
147
42.6%
|
| No Walking Aid at Baseline - Cycle 4 |
40
11.6%
|
| Walking Aid at Baseline - Cycle 4 |
99
28.7%
|
| No Walking Aid at Week 4 - Cycle 4 |
33
9.6%
|
| Walking Aid at Week 4 - Cycle 4 |
64
18.6%
|
Adverse Events
| Time Frame | From baseline to EOS (maximum duration of 52 weeks). | |
|---|---|---|
| Adverse Event Reporting Description | AE data is reported as TEAEs. An AE was reported as a TEAE if it arose or the intensity increased during the treatment phase of this study. | |
| Arm/Group Title | Total Dysport® | |
| Arm/Group Description | Subjects who had completed Study 140 were offered to continue to receive open label treatment with Dysport® in Study 142 for a maximum of 4 additional treatment cycles, with a minimum interval of 12 weeks between treatment cycles. All subjects were administered an appropriate dosage of Dysport® (1500 U or 1000 U) by i.m. injection in the lower limb on Day 1 of treatment Cycle 1. In all cases, the administration of the Dysport® injections was limited to a maximum dose of 1500 U every 12 weeks. Follow up visits were timed to assess the onset and progression of treatment response. From treatment Cycle 3 onwards, subjects with co-existing upper limb spasticity were able to receive concomitant injections of Dysport® into at least one upper limb muscle at a dose not exceeding 500 U. Dysport® contains the neurotoxin Clostridium botulinum type A toxin-haemagglutinin complex (abobotulinumtoxinA). | |
All Cause Mortality |
||
| Total Dysport® | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Total Dysport® | ||
| Affected / at Risk (%) | # Events | |
| Total | 43/345 (12.5%) | |
| Cardiac disorders | ||
| Atrial fibrillation | 1/345 (0.3%) | 1 |
| Coronary artery dissection | 1/345 (0.3%) | 1 |
| Acute myocardial infarction | 1/345 (0.3%) | 1 |
| Coronary artery disease | 1/345 (0.3%) | 1 |
| Myocardial infarction | 1/345 (0.3%) | 1 |
| Gastrointestinal disorders | ||
| Dysphagia | 2/345 (0.6%) | 2 |
| Dyspepsia | 1/345 (0.3%) | 1 |
| Diarrhoea | 1/345 (0.3%) | 1 |
| Intestinal polyp | 1/345 (0.3%) | 1 |
| General disorders | ||
| Asthenia | 1/345 (0.3%) | 1 |
| Gait disturbance | 2/345 (0.6%) | 2 |
| Chest pain | 1/345 (0.3%) | 1 |
| Hepatobiliary disorders | ||
| Cholecystitis | 1/345 (0.3%) | 1 |
| Cholecystitis acute | 1/345 (0.3%) | 1 |
| Infections and infestations | ||
| Pneumonia | 3/345 (0.9%) | 3 |
| Bronchitis | 1/345 (0.3%) | 1 |
| Anal abscess | 1/345 (0.3%) | 1 |
| Appendicitis | 1/345 (0.3%) | 1 |
| Urinary tract infection | 1/345 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||
| Subdural haemorrhage | 1/345 (0.3%) | 1 |
| Wrist fracture | 1/345 (0.3%) | 1 |
| Concussion | 1/345 (0.3%) | 1 |
| Head injury | 1/345 (0.3%) | 1 |
| Fibula fracture | 1/345 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Intervertebral disc degeneration | 1/345 (0.3%) | 1 |
| Muscular weakness | 3/345 (0.9%) | 3 |
| Nervous system disorders | ||
| Cerebral haemorrhage | 2/345 (0.6%) | 2 |
| Presyncope | 1/345 (0.3%) | 1 |
| Epilepsy | 5/345 (1.4%) | 5 |
| Syncope | 2/345 (0.6%) | 2 |
| Transient ischaemic attack | 1/345 (0.3%) | 1 |
| Seizure | 1/345 (0.3%) | 1 |
| Cerebrovascular accident | 1/345 (0.3%) | 1 |
| Psychiatric disorders | ||
| Completed suicide | 1/345 (0.3%) | 1 |
| Anxiety | 1/345 (0.3%) | 1 |
| Suicidal ideation | 1/345 (0.3%) | 1 |
| Suicide attempt | 1/345 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Haemothorax | 1/345 (0.3%) | 1 |
| Pulmonary embolism | 1/345 (0.3%) | 2 |
| Pleural effusion | 1/345 (0.3%) | 1 |
| Dyspnoea | 1/345 (0.3%) | 1 |
| Respiratory failure | 1/345 (0.3%) | 1 |
| Vascular disorders | ||
| Venous thrombosis | 1/345 (0.3%) | 1 |
| Haematoma | 1/345 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Total Dysport® | ||
| Affected / at Risk (%) | # Events | |
| Total | 69/345 (20%) | |
| Injury, poisoning and procedural complications | ||
| Fall | 42/345 (12.2%) | 52 |
| Musculoskeletal and connective tissue disorders | ||
| Muscular weakness | 36/345 (10.4%) | 41 |
Limitations/Caveats
Data is summarised according to total dose received at each corresponding cycle (i.e. including 1000 U and 1500 U Dysport® in lower limb during all cycles, as well as 1000 U in lower limb + 500 U Dysport® in upper limb during Cycles 3 and 4).
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Medical Director, Neurology, |
|---|---|
| Organization | Ipsen |
| Phone | |
| clinical.trials@ipsen.com |
Responsible Party:
Ipsen
ClinicalTrials.gov Identifier:
NCT01251367
Other Study ID Numbers:
- Y-55-52120-142
- 2009-017723-26
First Posted:
Dec 1, 2010
Last Update Posted:
Nov 22, 2019
Last Verified:
Nov 1, 2019