Nervous System Disorders
Conditions
Brief summary
The purpose of this research study is to assess the efficacy of Dysport compared to placebo in improving muscle tone in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury.
Interventions
BIOLOGICALBotulinum toxin type A
500 U, I.M. (in the muscle) injection on day 1 of a single treatment cycle.
DRUGPlacebo
I.M. (in the muscle) injection on day 1 of a single treatment cycle.
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients - post stroke or brain injury * Modified Ashworth Scale ≥ 2 * Ambulatory patients
Exclusion criteria
* Previous treatment with botulinum toxin of any type within 4 months prior to study entry for any condition * Physiotherapy initiated less than 4 weeks before inclusion * Previous surgery, alcohol, phenol in upper limb * Neurological/neuromuscular disorders which may interfere with protocol evaluations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MAS Score in the Primary Targeted Muscle Group (PTMG) | From Baseline (Day 1) to Week 4 | MAS scale is used to assess muscle tone using a 6-point scale where: 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) when the part is flexed or extended, 1±Slight increase in muscle tone manifested by a catch followed by minimal resistance throughout the remainder of the ROM, 2=Marked increase in muscle tone through most of the ROM but affected part easily moved, 3=Considerable increase in muscle tone passive movement difficult or 4=Affected part(s) rigid in flexion or extension. The MAS has been derived for analyses as follows: 0=0 ; 1=1; 1+=2; 2=3; 3=4 and 4=5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Global Assessment (PGA) of Treatment Response | At Week 4 | PGA is a 9-point scale used to assess global overall treatment response by the investigator (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). |
| Change From Baseline in DAS Score for the Principal Target of Treatment (PTT) | From Baseline (Day 1) to Week 4 | DAS is a 4-point scale used to determine the extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain). DAS scale rating: 0=No disability, 1=Mild disability (noticeable but does not interfere significantly with normal activities), 2=Moderate disability (normal activities require increased effort and/or assistance) and 3=Severe disability (normal activities limited). If subject chose 'Hygiene' as PTT the score collected will be between 0 and 3. |
Countries
Belgium, Czechia, France, Hungary, Italy, Poland, Russia, Slovakia, United States
Participant flow
Recruitment details
This multicenter study was conducted in 34 investigational sites. Subjects screened were 281 and randomised and treated were 243.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo intramuscular injection single treatment cycle on day 1 | 81 |
| Dysport 500 U Botulinum type A toxin (Dysport) 500 U intramuscular injection single treatment cycle on day 1 | 81 |
| Dysport 1000 U Botulinum type A toxin (Dysport) 1000 U intramuscular injection single treatment cycle on day 1 | 81 |
| Total | 243 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 1 |
| Overall Study | Family reason and moved out of state | 0 | 2 | 0 |
| Overall Study | Lack of subject compliance | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Dysport 500 U | Dysport 1000 U | Total |
|---|---|---|---|---|
| Age, Continuous | 52.9 years STANDARD_DEVIATION 13.8 | 52.8 years STANDARD_DEVIATION 12.8 | 53.2 years STANDARD_DEVIATION 13.8 | 52.9 years STANDARD_DEVIATION 13.4 |
| Body Mass Index (BMI) | 26.78 kg/m2 STANDARD_DEVIATION 5.38 | 27.63 kg/m2 STANDARD_DEVIATION 4.61 | 27.58 kg/m2 STANDARD_DEVIATION 5.51 | 27.33 kg/m2 STANDARD_DEVIATION 5.17 |
| Disability Assessment Scale (DAS) | 2.6 units on a scale STANDARD_DEVIATION 0.5 | 2.6 units on a scale STANDARD_DEVIATION 0.5 | 2.5 units on a scale STANDARD_DEVIATION 0.5 | 2.6 units on a scale STANDARD_DEVIATION 0.5 |
| Ethnicity Hispanic/Latino | 5 participants | 3 participants | 10 participants | 18 participants |
| Ethnicity Not Hispanic/Latino | 76 participants | 78 participants | 71 participants | 225 participants |
| Modified Ashworth Scale (MAS) | 3.9 units on a scale STANDARD_DEVIATION 0.4 | 3.9 units on a scale STANDARD_DEVIATION 0.5 | 3.9 units on a scale STANDARD_DEVIATION 0.4 | 3.9 units on a scale STANDARD_DEVIATION 0.4 |
| Race/Ethnicity, Customized Asian | 1 participants | 3 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized Black/African American | 9 participants | 7 participants | 11 participants | 27 participants |
| Race/Ethnicity, Customized Caucasian/White | 71 participants | 70 participants | 67 participants | 208 participants |
| Race/Ethnicity, Customized Multiple | 0 participants | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 31 Participants | 28 Participants | 28 Participants | 87 Participants |
| Sex: Female, Male Male | 50 Participants | 53 Participants | 53 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 81 | 25 / 81 | 18 / 81 |
| serious Total, serious adverse events | 3 / 81 | 3 / 81 | 3 / 81 |
Outcome results
Primary
Change From Baseline in MAS Score in the Primary Targeted Muscle Group (PTMG)
MAS scale is used to assess muscle tone using a 6-point scale where: 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) when the part is flexed or extended, 1±Slight increase in muscle tone manifested by a catch followed by minimal resistance throughout the remainder of the ROM, 2=Marked increase in muscle tone through most of the ROM but affected part easily moved, 3=Considerable increase in muscle tone passive movement difficult or 4=Affected part(s) rigid in flexion or extension. The MAS has been derived for analyses as follows: 0=0 ; 1=1; 1+=2; 2=3; 3=4 and 4=5.
Time frame: From Baseline (Day 1) to Week 4
Population: Intention to treat (ITT) population included all randomized subjects who received at least one injection of study drug and had a MAS score at baseline (pretreatment) and at week 4. Total 5 subjects were excluded from ITT population as they did not have MAS score at baseline or/and at week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in MAS Score in the Primary Targeted Muscle Group (PTMG) | -0.3 units on a scale | Standard Deviation 0.6 |
| Dysport 500 U | Change From Baseline in MAS Score in the Primary Targeted Muscle Group (PTMG) | -1.2 units on a scale | Standard Deviation 1 |
| Dysport 1000 U | Change From Baseline in MAS Score in the Primary Targeted Muscle Group (PTMG) | -1.4 units on a scale | Standard Deviation 1.1 |
Secondary
Change From Baseline in DAS Score for the Principal Target of Treatment (PTT)
DAS is a 4-point scale used to determine the extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain). DAS scale rating: 0=No disability, 1=Mild disability (noticeable but does not interfere significantly with normal activities), 2=Moderate disability (normal activities require increased effort and/or assistance) and 3=Severe disability (normal activities limited). If subject chose 'Hygiene' as PTT the score collected will be between 0 and 3.
Time frame: From Baseline (Day 1) to Week 4
Population: ITT population. Two subjects each from Placebo and Dysport 1000 U had missed DAS assessment at baseline and week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in DAS Score for the Principal Target of Treatment (PTT) | -0.5 units on a scale | Standard Deviation 0.7 |
| Dysport 500 U | Change From Baseline in DAS Score for the Principal Target of Treatment (PTT) | -0.7 units on a scale | Standard Deviation 0.8 |
| Dysport 1000 U | Change From Baseline in DAS Score for the Principal Target of Treatment (PTT) | -0.7 units on a scale | Standard Deviation 0.7 |
Secondary
Physician's Global Assessment (PGA) of Treatment Response
PGA is a 9-point scale used to assess global overall treatment response by the investigator (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved).
Time frame: At Week 4
Population: ITT population. Two subjects each from Placebo and Dysport 1000 U had missed PGA assessment at week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Physician's Global Assessment (PGA) of Treatment Response | 0.6 units on a scale | Standard Deviation 1 |
| Dysport 500 U | Physician's Global Assessment (PGA) of Treatment Response | 1.4 units on a scale | Standard Deviation 1.1 |
| Dysport 1000 U | Physician's Global Assessment (PGA) of Treatment Response | 1.8 units on a scale | Standard Deviation 1.1 |