Upper Limb Spasticity
Conditions
Brief summary
This study will investigate the efficacy and safety of incobotulinumtoxinA (Xeomin) in the treatment of arm tightness (upper limb spasticity) using two different dilutions of incobotulinumtoxinA (Xeomin).
Detailed description
IncobotulinumtoxinA (Xeomin) is a botulinum toxin type A preparation free of complexing proteins. Injected into a muscle, incobotulinumtoxinA causes a reversible local weakening of the muscle for several months, and may improve an impaired muscle function by lessening the muscle tightness within few days. IncobotulinumtoxinA is widely used for various severe neurological conditions. There is some evidence that the treatment effect may be influenced by the amount of the solvent in which incobotulinumtoxinA is diluted before injection.
Interventions
DRUGincobotulinumtoxinA (Xeomin, also known as NT 201 or Botulinum toxin type A (150 kD), free from complexing proteins)
active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins; powder for solution for injection; Mode of administration: intramuscular injection; The content of the vial was dissolved in 2.0 or 5.0 mL of sterile sodium chloride \[NaCl\] 0.9% solution without preservatives. Dilution with 2.0 or 5.0 mL resulted in a dose of 50 or 20 units per 1.0 mL.
Sponsors
Merz Pharmaceuticals GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Female or male patients ≥ 18 years * Stable upper limb spasticity of diverse etiology * Focal spasticity with equal or more than 2 points on the Ashworth scale in the wrist flexors * Disability Assessment Scale (DAS) ≥ 2 points for primary therapeutic target at both screening and baseline visits Main
Exclusion criteria
* Fixed contracture * Bilateral upper limb paresis/paralysis * Previous treatment with BoNT of any serotype and for any body region within the 4 months prior to screening * Previous or planned treatment with phenol- or alcohol-injection in the target limb * Other muscle hypertonia (e.g. rigidity) * Diagnosis of myasthenia gravis, Lambert-Eaton-Syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease which might interfere with the study * Severe atrophy of the target limb muscles
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder in Disability Assessment Scale (DAS) at Week 4 - Per Protocol Set | At week 4 | The primary efficacy endpoint is the number of responder at Week 4; response defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit to Week 4. The DAS determines the functional impairment for the domains hygiene, dressing, limb position and pain according to the following scale: 0 = no disability; 1 = mild disability; 2 = moderate disability; 3 = severe disability. At Screening visit, the subject and investigator, selected together one of the four domains as the primary therapeutic target. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder in DAS at Week 12 - Full Analysis Set | week 12 | Response is defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit. |
| Responder in DAS at Follow up - Full Analysis Set | follow up visit, between week 12 and week 20 | Response is defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit. |
| Responder in Frenchay Arm Test (FAT) at Week 4 - Full Analysis Set | Week 4 | Response is defined as an improvement (increase) of at least one point in the FAT from baseline visit. For the FAT the investigator assessed the extent of functionality of the upper limb according to five standardized tests. Each test is rated with 0 = failed or 1 = successfully passed. For the evaluation, the sum of all test scores was calculated resulting in a total score from 0 to 5. |
| Responder in FAT at Week 12 - Full Analysis Set | Week 12 | Response is defined as an improvement (increase) of at least one point in the FAT from baseline visit. For the FAT the investigator assessed the extent of functionality of the upper limb according to five standardized tests. Each test is rated with 0 = failed or 1 = successfully passed. For the evaluation, the sum of all test scores was calculated resulting in a total score from 0 to 5. |
| Responder in FAT at Follow up - Full Analysis Set | follow up visit, between week 12 and week 20 | Response is defined as an improvement (increase) of at least one point in the FAT from baseline visit. For the FAT the investigator assessed the extent of functionality of the upper limb according to five standardized tests. Each test is rated with 0 = failed or 1 = successfully passed. For the evaluation, the sum of all test scores was calculated resulting in a total score from 0 to 5. |
| Responder in Ashworth Scale (Elbow Flexors) at Week 4 - Full Analysis Set | week 4 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. The Ashworth Scale is a 5-point-scale to rate to degree of spasticity: 0 = No increase in tone; 1 = Slight increase in tone giving a catch when the limb was moved in flexion or extension; 2 = More marked increase in tone, but limb easily flexed; 3 = Considerable increase in tone - passive movements difficult; 4 = Limb rigid in flexion or extension. |
| Responder in Ashworth Scale (Elbow Flexors) at Week 12 - Full Analysis Set | week 12 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Elbow Flexors) at Follow up - Full Analysis Set | follow up visit, between week 12 and week 20 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Wrist Flexors) at Week 4 - Full Analysis Set | week 4 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Wrist Flexors) at Week 12 - Full Analysis Set | week 12 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Wrist Flexors) at Follow up - Full Analysis Set | follow up visit, between week 12 and week 20 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Thumb Flexors) at Week 4 - Full Analysis Set | week 4 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Thumb Flexors) at Week 12 - Full Analysis Set | week 12 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Thumb Flexors) at Follow up - Full Analysis Set | follow up visit, between week 12 and week 20 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Fingers Flexors) at Week 4 - Full Analysis Set | week 4 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Fingers Flexors) at Week 12 - Full Analysis Set | week 12 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Fingers Flexors) at Follow up - Full Analysis Set | follow up visit, between week 12 and week 20 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Forearm Pronators) at Week 4 - Full Analysis Set | week 4 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Forearm Pronators) at Week 12 - Full Analysis Set | week 12 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Responder in Ashworth Scale (Forearm Pronators) at Follow up - Full Analysis Set | follow up visit, between week 12 and week 20 | Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. |
| Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension | baseline, week 4, week 12, follow up (between week 12 and week 20) | For the PROM all motions of wrist and elbow were measured from a defined neutral starting point position. The degrees of motion were added in the direction the wrist and elbow moved from the neutral starting position. The neutral starting position was the position of an upright standing/sitting person. The angle of the motion from the neutral starting position was measured in degrees using a goniometer. Angles were measured for the wrist with maximal dorsal extension, neutral position and maximal palmar flexion, and for the elbow with maximal extension, neutral position and maximal flexion. |
| Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension | baseline, week 4, week 12, follow up (between week 12 and week 20) | For the PROM all motions of wrist and elbow were measured from a defined neutral starting point position. The degrees of motion were added in the direction the wrist and elbow moved from the neutral starting position. The neutral starting position was the position of an upright standing/sitting person. The angle of the motion from the neutral starting position was measured in degrees using a goniometer. Angles were measured for the wrist with maximal dorsal extension, neutral position and maximal palmar flexion, and for the elbow with maximal extension, neutral position and maximal flexion. |
| Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion | baseline, week 4, week 12, follow up (between week 12 and week 20) | For the PROM all motions of wrist and elbow were measured from a defined neutral starting point position. The degrees of motion were added in the direction the wrist and elbow moved from the neutral starting position. The neutral starting position was the position of an upright standing/sitting person. The angle of the motion from the neutral starting position was measured in degrees using a goniometer. Angles were measured for the wrist with maximal dorsal extension, neutral position and maximal palmar flexion, and for the elbow with maximal extension, neutral position and maximal flexion. |
| Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion | baseline, week 4, week 12, follow up (between week 12 and week 20) | For the PROM all motions of wrist and elbow were measured from a defined neutral starting point position. The degrees of motion were added in the direction the wrist and elbow moved from the neutral starting position. The neutral starting position was the position of an upright standing/sitting person. The angle of the motion from the neutral starting position was measured in degrees using a goniometer. Angles were measured for the wrist with maximal dorsal extension, neutral position and maximal palmar flexion, and for the elbow with maximal extension, neutral position and maximal flexion. |
| Investigator's Global Assessment of Treatment Response (GATR) - Full Analysis Set | week 4 | The investigator's global assessment of response to treatment were determined with the use of the Global Response Scale using the following scores: -4 = very marked worsening; -3 = marked worsening; -2 = moderate worsening; -1 = mild worsening; 0 = no change; +1 = mild improvement; +2 = moderate improvement; +3 = marked improvement; +4 = very marked improvement. |
| Patient's Global Assessment of Treatment Response (GATR) - Full Analysis Set | week 4 | The patient's global assessment of response to treatment were determined with the use of the Global Response Scale using the following scores: -4 = very marked worsening; -3 = marked worsening; -2 = moderate worsening; -1 = mild worsening; 0 = no change; +1 = mild improvement; +2 = moderate improvement; +3 = marked improvement; +4 = very marked improvement. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Feeding | week 4 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Feeding | week 12 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Feeding | follow up visit, between week 12 and week 20 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Grooming | week 4 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Grooming | week 12 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Grooming | follow up visit, between week 12 and week 20 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Toilet Use | week 4 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Toilet Use | week 12 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Toilet Use | follow up visit, between week 12 and week 20 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Bathing/Showering | week 4 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Responder in DAS at Week 4 - Full Analysis Set | week 4 | Response is defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit. |
| Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Bathing/Showering | follow up visit, between week 12 and week 20 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Dressing | week 4 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Dressing | week 12 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Dressing | follow up visit, between week 12 and week 20 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
| Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Bathing/Showering | week 12 | Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent. |
Countries
Austria, France, Germany, Italy, Portugal, Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
216 female and male subjects with upper limb spasticity caused by either stroke, brain injury, spinal cord injury, multiple sclerosis or cerebral palsy were screened starting February 2007. Recruitment advertisements according to local law and approved by the responsible IEC were published as needed.
Pre-assignment details
The protocol contained a screening period of 7 days to allow evaluation of laboratory and ECGs in order to determine eligibility. 24 subjects were screening failures due to violation of selection or protocol criteria.
Participants by arm
| Arm | Count |
|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | 97 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | 95 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other | 2 | 5 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Total |
|---|---|---|---|
| Age Continuous | 55.3 years STANDARD_DEVIATION 14.88 | 55.5 years STANDARD_DEVIATION 13.74 | 55.4 years STANDARD_DEVIATION 14.29 |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Caucasian | 76 participants | 78 participants | 154 participants |
| Race/Ethnicity, Customized Missing | 18 participants | 16 participants | 34 participants |
| Race/Ethnicity, Customized Negroid | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Oriental | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 48 Participants | 33 Participants | 81 Participants |
| Sex: Female, Male Male | 49 Participants | 62 Participants | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 96 | 17 / 96 |
| serious Total, serious adverse events | 6 / 96 | 6 / 96 |
Outcome results
Primary
Responder in Disability Assessment Scale (DAS) at Week 4 - Per Protocol Set
The primary efficacy endpoint is the number of responder at Week 4; response defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit to Week 4. The DAS determines the functional impairment for the domains hygiene, dressing, limb position and pain according to the following scale: 0 = no disability; 1 = mild disability; 2 = moderate disability; 3 = severe disability. At Screening visit, the subject and investigator, selected together one of the four domains as the primary therapeutic target.
Time frame: At week 4
Population: Analysis is based on Per Protocol Set, defined as all randomized subjects who received at least one dose of study drug and who have no major deviation from study protocol. For this set of subjects no missing values can occur for the primary endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Disability Assessment Scale (DAS) at Week 4 - Per Protocol Set | 51 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Disability Assessment Scale (DAS) at Week 4 - Per Protocol Set | 44 participants |
Comparison: Null hypothesis: The response rate for the low volume dilution group (50 U/ml) is greater than the response rate for the high volume dilution group (20 U/ml).95% CI: [-4.4, 24.9]
Secondary
Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension
For the PROM all motions of wrist and elbow were measured from a defined neutral starting point position. The degrees of motion were added in the direction the wrist and elbow moved from the neutral starting position. The neutral starting position was the position of an upright standing/sitting person. The angle of the motion from the neutral starting position was measured in degrees using a goniometer. Angles were measured for the wrist with maximal dorsal extension, neutral position and maximal palmar flexion, and for the elbow with maximal extension, neutral position and maximal flexion.
Time frame: baseline, week 4, week 12, follow up (between week 12 and week 20)
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension | Week 4 | 8.0 degree | Standard Error 3.37 |
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension | Week 12 | 6.1 degree | Standard Error 4.5 |
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension | Follow up (between week 12 and week 20) | 3.9 degree | Standard Error 3.58 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension | Week 4 | 5.8 degree | Standard Error 3.42 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension | Week 12 | 2.1 degree | Standard Error 4.46 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Extension | Follow up (between week 12 and week 20) | 4.1 degree | Standard Error 3.58 |
Secondary
Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion
For the PROM all motions of wrist and elbow were measured from a defined neutral starting point position. The degrees of motion were added in the direction the wrist and elbow moved from the neutral starting position. The neutral starting position was the position of an upright standing/sitting person. The angle of the motion from the neutral starting position was measured in degrees using a goniometer. Angles were measured for the wrist with maximal dorsal extension, neutral position and maximal palmar flexion, and for the elbow with maximal extension, neutral position and maximal flexion.
Time frame: baseline, week 4, week 12, follow up (between week 12 and week 20)
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion | Week 4 | 0.1 degree | Standard Error 2.6 |
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion | Week 12 | -0.7 degree | Standard Error 2.45 |
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion | Follow up (between week 12 and week 20) | -1.9 degree | Standard Error 2.86 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion | Week 4 | 2.7 degree | Standard Error 2.6 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion | Week 12 | 2.6 degree | Standard Error 2.41 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Elbow Maximum Flexion | Follow up (between week 12 and week 20) | 1.0 degree | Standard Error 2.81 |
Secondary
Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension
For the PROM all motions of wrist and elbow were measured from a defined neutral starting point position. The degrees of motion were added in the direction the wrist and elbow moved from the neutral starting position. The neutral starting position was the position of an upright standing/sitting person. The angle of the motion from the neutral starting position was measured in degrees using a goniometer. Angles were measured for the wrist with maximal dorsal extension, neutral position and maximal palmar flexion, and for the elbow with maximal extension, neutral position and maximal flexion.
Time frame: baseline, week 4, week 12, follow up (between week 12 and week 20)
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension | Week 4 | 14.8 degree | Standard Error 3.31 |
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension | Week 12 | 7.3 degree | Standard Error 3.15 |
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension | Follow up (between week 12 and week 20) | 8.2 degree | Standard Error 4.62 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension | Week 4 | 15.7 degree | Standard Error 3.47 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension | Week 12 | 10.4 degree | Standard Error 3.32 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Extension | Follow up (between week 12 and week 20) | 10.4 degree | Standard Error 4.93 |
Secondary
Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion
For the PROM all motions of wrist and elbow were measured from a defined neutral starting point position. The degrees of motion were added in the direction the wrist and elbow moved from the neutral starting position. The neutral starting position was the position of an upright standing/sitting person. The angle of the motion from the neutral starting position was measured in degrees using a goniometer. Angles were measured for the wrist with maximal dorsal extension, neutral position and maximal palmar flexion, and for the elbow with maximal extension, neutral position and maximal flexion.
Time frame: baseline, week 4, week 12, follow up (between week 12 and week 20)
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion | Week 4 | -1.2 degree | Standard Error 2.34 |
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion | Week 12 | -1.3 degree | Standard Error 2.48 |
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion | Follow up (between week 12 and week 20) | -1.3 degree | Standard Error 2.62 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion | Week 4 | 5.2 degree | Standard Error 2.45 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion | Follow up (between week 12 and week 20) | 3.8 degree | Standard Error 2.8 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Change From Baseline in Passive Range of Motion (PROM) - Wrist Maximum Flexion | Week 12 | 2.9 degree | Standard Error 2.62 |
Secondary
Investigator's Global Assessment of Treatment Response (GATR) - Full Analysis Set
The investigator's global assessment of response to treatment were determined with the use of the Global Response Scale using the following scores: -4 = very marked worsening; -3 = marked worsening; -2 = moderate worsening; -1 = mild worsening; 0 = no change; +1 = mild improvement; +2 = moderate improvement; +3 = marked improvement; +4 = very marked improvement.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Investigator's Global Assessment of Treatment Response (GATR) - Full Analysis Set | 1.66 units on a scale | Standard Error 0.106 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Investigator's Global Assessment of Treatment Response (GATR) - Full Analysis Set | 1.59 units on a scale | Standard Error 0.106 |
Secondary
Patient's Global Assessment of Treatment Response (GATR) - Full Analysis Set
The patient's global assessment of response to treatment were determined with the use of the Global Response Scale using the following scores: -4 = very marked worsening; -3 = marked worsening; -2 = moderate worsening; -1 = mild worsening; 0 = no change; +1 = mild improvement; +2 = moderate improvement; +3 = marked improvement; +4 = very marked improvement.
Time frame: week 4
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Patient's Global Assessment of Treatment Response (GATR) - Full Analysis Set | 1.41 units on a scale | Standard Error 0.121 |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Patient's Global Assessment of Treatment Response (GATR) - Full Analysis Set | 1.48 units on a scale | Standard Error 0.121 |
Secondary
Responder in Ashworth Scale (Elbow Flexors) at Follow up - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Elbow Flexors) at Follow up - Full Analysis Set | 30 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Elbow Flexors) at Follow up - Full Analysis Set | 21 participants |
Secondary
Responder in Ashworth Scale (Elbow Flexors) at Week 12 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Elbow Flexors) at Week 12 - Full Analysis Set | 37 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Elbow Flexors) at Week 12 - Full Analysis Set | 40 participants |
Secondary
Responder in Ashworth Scale (Elbow Flexors) at Week 4 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit. The Ashworth Scale is a 5-point-scale to rate to degree of spasticity: 0 = No increase in tone; 1 = Slight increase in tone giving a catch when the limb was moved in flexion or extension; 2 = More marked increase in tone, but limb easily flexed; 3 = Considerable increase in tone - passive movements difficult; 4 = Limb rigid in flexion or extension.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Elbow Flexors) at Week 4 - Full Analysis Set | 47 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Elbow Flexors) at Week 4 - Full Analysis Set | 50 participants |
Secondary
Responder in Ashworth Scale (Fingers Flexors) at Follow up - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Fingers Flexors) at Follow up - Full Analysis Set | 17 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Fingers Flexors) at Follow up - Full Analysis Set | 20 participants |
Secondary
Responder in Ashworth Scale (Fingers Flexors) at Week 12 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Fingers Flexors) at Week 12 - Full Analysis Set | 35 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Fingers Flexors) at Week 12 - Full Analysis Set | 35 participants |
Secondary
Responder in Ashworth Scale (Fingers Flexors) at Week 4 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Fingers Flexors) at Week 4 - Full Analysis Set | 57 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Fingers Flexors) at Week 4 - Full Analysis Set | 48 participants |
Secondary
Responder in Ashworth Scale (Forearm Pronators) at Follow up - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Forearm Pronators) at Follow up - Full Analysis Set | 18 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Forearm Pronators) at Follow up - Full Analysis Set | 16 participants |
Secondary
Responder in Ashworth Scale (Forearm Pronators) at Week 12 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Forearm Pronators) at Week 12 - Full Analysis Set | 28 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Forearm Pronators) at Week 12 - Full Analysis Set | 22 participants |
Secondary
Responder in Ashworth Scale (Forearm Pronators) at Week 4 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Forearm Pronators) at Week 4 - Full Analysis Set | 32 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Forearm Pronators) at Week 4 - Full Analysis Set | 30 participants |
Secondary
Responder in Ashworth Scale (Thumb Flexors) at Follow up - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Thumb Flexors) at Follow up - Full Analysis Set | 18 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Thumb Flexors) at Follow up - Full Analysis Set | 9 participants |
Secondary
Responder in Ashworth Scale (Thumb Flexors) at Week 12 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Thumb Flexors) at Week 12 - Full Analysis Set | 21 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Thumb Flexors) at Week 12 - Full Analysis Set | 13 participants |
Secondary
Responder in Ashworth Scale (Thumb Flexors) at Week 4 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Thumb Flexors) at Week 4 - Full Analysis Set | 29 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Thumb Flexors) at Week 4 - Full Analysis Set | 19 participants |
Secondary
Responder in Ashworth Scale (Wrist Flexors) at Follow up - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Wrist Flexors) at Follow up - Full Analysis Set | 31 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Wrist Flexors) at Follow up - Full Analysis Set | 28 participants |
Secondary
Responder in Ashworth Scale (Wrist Flexors) at Week 12 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Wrist Flexors) at Week 12 - Full Analysis Set | 43 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Wrist Flexors) at Week 12 - Full Analysis Set | 46 participants |
Secondary
Responder in Ashworth Scale (Wrist Flexors) at Week 4 - Full Analysis Set
Response is defined as an improvement of at least one point in the Ashworth Scale for the treated muscle group from baseline visit.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Ashworth Scale (Wrist Flexors) at Week 4 - Full Analysis Set | 68 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Ashworth Scale (Wrist Flexors) at Week 4 - Full Analysis Set | 63 participants |
Secondary
Responder in DAS at Follow up - Full Analysis Set
Response is defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in DAS at Follow up - Full Analysis Set | 40 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in DAS at Follow up - Full Analysis Set | 33 participants |
Secondary
Responder in DAS at Week 12 - Full Analysis Set
Response is defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in DAS at Week 12 - Full Analysis Set | 46 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in DAS at Week 12 - Full Analysis Set | 38 participants |
Secondary
Responder in DAS at Week 4 - Full Analysis Set
Response is defined as an improvement (reduction) of at least one point in the DAS for the primary therapeutic target from baseline visit.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in DAS at Week 4 - Full Analysis Set | 59 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in DAS at Week 4 - Full Analysis Set | 49 participants |
Secondary
Responder in FAT at Follow up - Full Analysis Set
Response is defined as an improvement (increase) of at least one point in the FAT from baseline visit. For the FAT the investigator assessed the extent of functionality of the upper limb according to five standardized tests. Each test is rated with 0 = failed or 1 = successfully passed. For the evaluation, the sum of all test scores was calculated resulting in a total score from 0 to 5.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in FAT at Follow up - Full Analysis Set | 12 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in FAT at Follow up - Full Analysis Set | 15 participants |
Secondary
Responder in FAT at Week 12 - Full Analysis Set
Response is defined as an improvement (increase) of at least one point in the FAT from baseline visit. For the FAT the investigator assessed the extent of functionality of the upper limb according to five standardized tests. Each test is rated with 0 = failed or 1 = successfully passed. For the evaluation, the sum of all test scores was calculated resulting in a total score from 0 to 5.
Time frame: Week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in FAT at Week 12 - Full Analysis Set | 20 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in FAT at Week 12 - Full Analysis Set | 22 participants |
Secondary
Responder in Frenchay Arm Test (FAT) at Week 4 - Full Analysis Set
Response is defined as an improvement (increase) of at least one point in the FAT from baseline visit. For the FAT the investigator assessed the extent of functionality of the upper limb according to five standardized tests. Each test is rated with 0 = failed or 1 = successfully passed. For the evaluation, the sum of all test scores was calculated resulting in a total score from 0 to 5.
Time frame: Week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Responder in Frenchay Arm Test (FAT) at Week 4 - Full Analysis Set | 17 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Responder in Frenchay Arm Test (FAT) at Week 4 - Full Analysis Set | 24 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Bathing/Showering
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Bathing/Showering | 2 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Bathing/Showering | 4 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Dressing
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Dressing | 8 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Dressing | 7 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Feeding
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Feeding | 7 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Feeding | 5 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Grooming
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Grooming | 7 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Grooming | 6 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Toilet Use
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: follow up visit, between week 12 and week 20
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Toilet Use | 11 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Follow up - Item Toilet Use | 5 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Bathing/Showering
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Bathing/Showering | 4 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Bathing/Showering | 6 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Dressing
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Dressing | 10 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Dressing | 8 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Feeding
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Feeding | 8 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Feeding | 6 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Grooming
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Grooming | 7 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Grooming | 10 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Toilet Use
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 12
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Toilet Use | 11 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 12 - Item Toilet Use | 7 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Bathing/Showering
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Bathing/Showering | 1 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Bathing/Showering | 7 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Dressing
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Dressing | 9 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Dressing | 6 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Feeding
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Feeding | 7 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Feeding | 5 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Grooming
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Grooming | 5 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Grooming | 6 participants |
Secondary
Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Toilet Use
Response is defined as an improvement (increase) of at least one point in the Barthel Index from baseline visit. The Barthel Index was assessed for the items feeding, grooming, toilet use, bathing and dressing. Feeding: 0 = unable; 1 = needs help cutting, spreading butter etc.; 2 = independent; Grooming: 0 = needs help with personal care; 1 = independent face/hair/teeth/shaving; Toilet use: 1 = need some help, but could do something alone; 2 = independent; Bathing: 0 = dependent; 1 = independent; Dressing: 0 = dependent; 1 = needs help but could do about half unaided; 2 = independent.
Time frame: week 4
Population: Analysis is based on Full Analysis Set, defined as all randomized subjects who received at least one dose of study drug. Missing values were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| incobotulinumtoxinA (Xeomin) High-volume Dilution 20 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Toilet Use | 7 participants |
| incobotulinumtoxinA (Xeomin) Low-volume Dilution 50 Units/mL | Response Rates in Activity of Daily Living (Barthel Index) at Week 4 - Item Toilet Use | 6 participants |