Motor Neuron Disease, Muscle Spasticity, Stroke
Conditions
Brief summary
The purpose of this study is to evaluate the safety of injections of botulinum toxin Type A in patients with reduced lung function and focal upper limb poststroke spasticity
Interventions
BIOLOGICALbotulinum toxin Type A
botulinum toxin Type A 240 U injection on Day 1, Week 12, Week 18
DRUGsaline
Saline injection at Day 1, Week 12, Week 18
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Abnormal pulmonary function test results; * focal, upper limb spasticity, upper motor neuron syndrome
Exclusion criteria
* Previous exposure to botulinum toxin of any serotype
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Vital Capacity (FVC) | Baseline, Week 6 | Change from baseline in observed FVC. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded at Baseline and Week 6. |
| Change From Baseline in Forced Expiratory Volume (FEV1) | Baseline, Week 6 | Change from baseline in observed FEV1 at one second. FEV1 is the maximum amount of air exhaled in one second. Patients perform three to eight exhalations into a spirometer with the highest value recorded at Baseline and Week 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1/FVC Ratio | Baseline, Week 6 | Change from baseline in FEV1/FVC ratio. This ratio is calculated by dividing the FEV1 value by the FVC value. This represents that portion (or ratio) of FVC exhaled in one second. |
| Change From Baseline in Ashworth Scale | Baseline, Week 6 | Change from Baseline in worst upper limb scores using the Ashworth Scale at Week 6 from Baseline. Upper limb includes finger, wrist, thumb, and elbow. Worst score was the highest value measured from the finger, wrist, thumb, or elbow at Baseline and Week 6 based on treated areas. The Ashworth Scale assesses the degree of muscle tone. It is a 5-point scale where 0 equals no increase in muscle tone and 4 equals very severe muscle rigidity. A low score indicates little or no stiffness. A high score indicates severe stiffness. A negative change from baseline score indicates improvement. |
Countries
Czechia, Hungary, Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo | 48 |
| Botulinum Toxin Type A 240 U botulinum toxin Type A 240 U | 52 |
| Botulinum Toxin Type A 360 U botulinum toxin Type A 360 U | 55 |
| Total | 155 |
Baseline characteristics
| Characteristic | Placebo | Botulinum Toxin Type A 240 U | Botulinum Toxin Type A 360 U | Total |
|---|---|---|---|---|
| Age Continuous | 58 years | 55.5 years | 55.8 years | 56.4 years |
| Sex: Female, Male Female | 19 Participants | 13 Participants | 21 Participants | 53 Participants |
| Sex: Female, Male Male | 29 Participants | 39 Participants | 34 Participants | 102 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 | 18 / 48 | 15 / 52 | 17 / 55 |
| serious Total, serious adverse events | 7 / 48 | 9 / 52 | 6 / 55 |
Outcome results
Primary
Change From Baseline in Forced Expiratory Volume (FEV1)
Change from baseline in observed FEV1 at one second. FEV1 is the maximum amount of air exhaled in one second. Patients perform three to eight exhalations into a spirometer with the highest value recorded at Baseline and Week 6.
Time frame: Baseline, Week 6
Population: Safety
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) | Baseline | 2.111 Liters of air | Standard Deviation 0.5944 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) | Change from Baseline at Week 6 | 0.049 Liters of air | Standard Deviation 0.1971 |
| Botulinum Toxin Type A 240 U | Change From Baseline in Forced Expiratory Volume (FEV1) | Baseline | 2.223 Liters of air | Standard Deviation 0.6492 |
| Botulinum Toxin Type A 240 U | Change From Baseline in Forced Expiratory Volume (FEV1) | Change from Baseline at Week 6 | 0.023 Liters of air | Standard Deviation 0.2925 |
| Botulinum Toxin Type A 360 U | Change From Baseline in Forced Expiratory Volume (FEV1) | Baseline | 2.168 Liters of air | Standard Deviation 0.6568 |
| Botulinum Toxin Type A 360 U | Change From Baseline in Forced Expiratory Volume (FEV1) | Change from Baseline at Week 6 | -0.008 Liters of air | Standard Deviation 0.234 |
Primary
Change From Baseline in Forced Vital Capacity (FVC)
Change from baseline in observed FVC. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded at Baseline and Week 6.
Time frame: Baseline, Week 6
Population: Safety
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 2.889 Liters of air | Standard Deviation 0.7804 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Change from Baseline at Week 6 | 0.057 Liters of air | Standard Deviation 0.3151 |
| Botulinum Toxin Type A 240 U | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.068 Liters of air | Standard Deviation 0.8766 |
| Botulinum Toxin Type A 240 U | Change From Baseline in Forced Vital Capacity (FVC) | Change from Baseline at Week 6 | 0.052 Liters of air | Standard Deviation 0.2883 |
| Botulinum Toxin Type A 360 U | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 2.923 Liters of air | Standard Deviation 0.7627 |
| Botulinum Toxin Type A 360 U | Change From Baseline in Forced Vital Capacity (FVC) | Change from Baseline at Week 6 | -0.081 Liters of air | Standard Deviation 0.2531 |
Secondary
Change From Baseline in Ashworth Scale
Change from Baseline in worst upper limb scores using the Ashworth Scale at Week 6 from Baseline. Upper limb includes finger, wrist, thumb, and elbow. Worst score was the highest value measured from the finger, wrist, thumb, or elbow at Baseline and Week 6 based on treated areas. The Ashworth Scale assesses the degree of muscle tone. It is a 5-point scale where 0 equals no increase in muscle tone and 4 equals very severe muscle rigidity. A low score indicates little or no stiffness. A high score indicates severe stiffness. A negative change from baseline score indicates improvement.
Time frame: Baseline, Week 6
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Ashworth Scale | Baseline | 3.19 Number on a scale | Standard Deviation 0.607 |
| Placebo | Change From Baseline in Ashworth Scale | Change from Baseline at Week 6 | -0.60 Number on a scale | Standard Deviation 0.564 |
| Botulinum Toxin Type A 240 U | Change From Baseline in Ashworth Scale | Baseline | 2.87 Number on a scale | Standard Deviation 0.561 |
| Botulinum Toxin Type A 240 U | Change From Baseline in Ashworth Scale | Change from Baseline at Week 6 | -1.01 Number on a scale | Standard Deviation 0.801 |
| Botulinum Toxin Type A 360 U | Change From Baseline in Ashworth Scale | Baseline | 2.96 Number on a scale | Standard Deviation 0.693 |
| Botulinum Toxin Type A 360 U | Change From Baseline in Ashworth Scale | Change from Baseline at Week 6 | -1.16 Number on a scale | Standard Deviation 0.834 |
Secondary
Change From Baseline in FEV1/FVC Ratio
Change from baseline in FEV1/FVC ratio. This ratio is calculated by dividing the FEV1 value by the FVC value. This represents that portion (or ratio) of FVC exhaled in one second.
Time frame: Baseline, Week 6
Population: Safety
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in FEV1/FVC Ratio | Baseline | 0.741 Ratio | Standard Deviation 0.132 |
| Placebo | Change From Baseline in FEV1/FVC Ratio | Change from Baseline at Week 6 | 0.000 Ratio | Standard Deviation 0.073 |
| Botulinum Toxin Type A 240 U | Change From Baseline in FEV1/FVC Ratio | Baseline | 0.731 Ratio | Standard Deviation 0.126 |
| Botulinum Toxin Type A 240 U | Change From Baseline in FEV1/FVC Ratio | Change from Baseline at Week 6 | -0.006 Ratio | Standard Deviation 0.0709 |
| Botulinum Toxin Type A 360 U | Change From Baseline in FEV1/FVC Ratio | Baseline | 0.742 Ratio | Standard Deviation 0.1051 |
| Botulinum Toxin Type A 360 U | Change From Baseline in FEV1/FVC Ratio | Change from Baseline at Week 6 | 0.019 Ratio | Standard Deviation 0.0699 |