Overactive Bladder
Conditions
Brief summary
This study will assess the safety and efficacy of botulinum toxin Type A for the treatment of urinary incontinence overactive bladder in patients with a spinal cord injury or multiple sclerosis.
Detailed description
Botulinum toxin Type A 300U has been discontinued from the study after regulatory approval of botulinum toxin Type A 200U. Patients remaining in the study who were allocated to receive botulinum toxin Type A 300U at treatment 2 (and had not yet received it) will receive botulinum toxin Type A 200U instead.
Interventions
BIOLOGICALbotulinum toxin Type A
Botulinum toxin Type A injection into the detrusor.
DRUGNormal Saline (Placebo)
Placebo (Normal Saline) injection into the detrusor.
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Urinary incontinence as a result of neurogenic overactive bladder due to spinal cord injury or multiple sclerosis * Inadequate response to anticholinergic medication used to treat overactive bladder. * Neurological respiratory impairment and abnormal pulmonary function test results
Exclusion criteria
* History or evidence of pelvic or urologic abnormality * Previous or current diagnosis of bladder or prostate cancer * Symptomatic or untreated urinary tract infection at time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1/FVC Ratio | Baseline, Week 6 | The FEV1/FVC ratio was calculated by dividing the FEV1 value by the FVC value representing the portion (or ratio) of FVC exhaled in one second. A positive change from Baseline indicated improvement. |
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline, Week 6 | Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FEV1, the maximum amount of air exhaled in one second, at Baseline and Week 6. The highest value at each time-point was recorded. A positive change from Baseline indicated improvement. |
| Change From Baseline in Forced Vital Capacity (FVC) | Baseline, Week 6 | Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible, at Baseline and Week 6. A positive change from Baseline indicated improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline, Week 6 | MCC (the maximum amount of urine the bladder could hold) was measured using urodynamic testing. The amount of urine collected was subtracted from the total volume infused measured as milliliters (mL) of urine. A positive change from Baseline indicated improvement (fuller bladder/ less incontinence). |
| Change From Baseline in the Number of Urinary Incontinence Episodes | Baseline, Week 6 | The number of urinary incontinence episodes or leakage occurring over the previous 3 days was recorded in the patient bladder diary at Baseline and prior to Week 6. A negative change from Baseline indicated improvement (less incontinence/leakage). |
| Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) | Baseline, Week 6 | MDP was measured at the first involuntary detrusor contraction using urodynamic testing. A catheter was inserted into the bladder at Baseline and Week 6 and the pressure \[measured in centimeters water (cm H20)\] was determined as the bladder filled. A negative change from Baseline indicated improvement (less Detrusor pressure). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least a 15% Decrease From Baseline in FVC | Baseline, Weeks 2, 6 and 12 | Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible at Baseline, Weeks 2, 6 and 12. |
| Number of Participants With at Least a 20% Decrease From Baseline in FVC | Baseline, Weeks 2, 6 and 12 | Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible at Baseline, Weeks 2, 6 and 12. |
Countries
Australia, Canada, India, United States
Participant flow
Pre-assignment details
Botulinum toxin Type A 300U was discontinued from the study after regulatory approval of botulinum toxin Type A 200U. Patients remaining in the study who were allocated to receive botulinum toxin Type A 300U at treatment 2 (and had not yet received it) received botulinum toxin Type A 200U instead.
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin Type A 200U Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable). | 15 |
| Botulinum Toxin Type A 300U Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable). | 14 |
| Placebo/Botulinum Toxin Type A Placebo (Normal Saline) injection into the detrusor on Day 1 followed by a botulinum toxin Type A 200U or 300U injection after a minimum of 12 weeks (if applicable). | 12 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Cycle 1 | Lost to Follow-up | 1 | 1 | 1 |
| Treatment Cycle 1 | Personal reasons | 0 | 2 | 0 |
| Treatment Cycle 1 | Withdrawal by Subject | 0 | 1 | 0 |
| Treatment Cycle 2 | Lost to Follow-up | 1 | 1 | 0 |
| Treatment Cycle 2 | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Botulinum Toxin Type A 200U | Botulinum Toxin Type A 300U | Placebo/Botulinum Toxin Type A |
|---|---|---|---|---|
| Age, Customized 40-64 Years | 16 participants | 4 participants | 6 participants | 6 participants |
| Age, Customized < 40 Years | 23 participants | 9 participants | 8 participants | 6 participants |
| Age, Customized ≥ 65 Years | 2 participants | 2 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 16 Participants | 7 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 25 Participants | 8 Participants | 8 Participants | 9 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 | 12 / 15 | 12 / 14 | 10 / 12 |
| serious Total, serious adverse events | 4 / 15 | 6 / 14 | 1 / 12 |
Outcome results
Primary
Change From Baseline in FEV1/FVC Ratio
The FEV1/FVC ratio was calculated by dividing the FEV1 value by the FVC value representing the portion (or ratio) of FVC exhaled in one second. A positive change from Baseline indicated improvement.
Time frame: Baseline, Week 6
Population: Safety population included all randomized participants who received treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A 200U | Change From Baseline in FEV1/FVC Ratio | Baseline | 0.857 Ratio | Standard Deviation 0.1093 |
| Botulinum Toxin Type A 200U | Change From Baseline in FEV1/FVC Ratio | Change from Baseline at Week 6 | 0.017 Ratio | Standard Deviation 0.0668 |
| Botulinum Toxin Type A 300U | Change From Baseline in FEV1/FVC Ratio | Baseline | 0.857 Ratio | Standard Deviation 0.1214 |
| Botulinum Toxin Type A 300U | Change From Baseline in FEV1/FVC Ratio | Change from Baseline at Week 6 | -0.007 Ratio | Standard Deviation 0.0578 |
| Placebo | Change From Baseline in FEV1/FVC Ratio | Baseline | 0.818 Ratio | Standard Deviation 0.1574 |
| Placebo | Change From Baseline in FEV1/FVC Ratio | Change from Baseline at Week 6 | -0.018 Ratio | Standard Deviation 0.0676 |
Primary
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FEV1, the maximum amount of air exhaled in one second, at Baseline and Week 6. The highest value at each time-point was recorded. A positive change from Baseline indicated improvement.
Time frame: Baseline, Week 6
Population: Safety population included all randomized participants who received treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A 200U | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline | 2.290 Liters | Standard Deviation 0.5815 |
| Botulinum Toxin Type A 200U | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Change from Baseline at Week 6 | -0.067 Liters | Standard Deviation 0.2525 |
| Botulinum Toxin Type A 300U | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline | 2.534 Liters | Standard Deviation 0.7227 |
| Botulinum Toxin Type A 300U | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Change from Baseline at Week 6 | -0.094 Liters | Standard Deviation 0.2196 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline | 2.535 Liters | Standard Deviation 0.7626 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Change from Baseline at Week 6 | -0.052 Liters | Standard Deviation 0.1926 |
Primary
Change From Baseline in Forced Vital Capacity (FVC)
Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible, at Baseline and Week 6. A positive change from Baseline indicated improvement.
Time frame: Baseline, Week 6
Population: Safety Population included all randomized participants who received treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A 200U | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 2.659 Liters | Standard Deviation 0.5308 |
| Botulinum Toxin Type A 200U | Change From Baseline in Forced Vital Capacity (FVC) | Change from Baseline at Week 6 | -0.124 Liters | Standard Deviation 0.2758 |
| Botulinum Toxin Type A 300U | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 2.955 Liters | Standard Deviation 0.7733 |
| Botulinum Toxin Type A 300U | Change From Baseline in Forced Vital Capacity (FVC) | Change from Baseline at Week 6 | -0.096 Liters | Standard Deviation 0.2248 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.095 Liters | Standard Deviation 0.6868 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Change from Baseline at Week 6 | -0.025 Liters | Standard Deviation 0.2391 |
Secondary
Change From Baseline in Maximum Cystometric Capacity (MCC)
MCC (the maximum amount of urine the bladder could hold) was measured using urodynamic testing. The amount of urine collected was subtracted from the total volume infused measured as milliliters (mL) of urine. A positive change from Baseline indicated improvement (fuller bladder/ less incontinence).
Time frame: Baseline, Week 6
Population: Intent-to-treat population included all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A 200U | Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline | 161.4 mL | Standard Deviation 80.29 |
| Botulinum Toxin Type A 200U | Change From Baseline in Maximum Cystometric Capacity (MCC) | Change from Baseline at Week 6 (n=12,13,11) | 213.2 mL | Standard Deviation 135.58 |
| Botulinum Toxin Type A 300U | Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline | 216.7 mL | Standard Deviation 168.41 |
| Botulinum Toxin Type A 300U | Change From Baseline in Maximum Cystometric Capacity (MCC) | Change from Baseline at Week 6 (n=12,13,11) | 60.2 mL | Standard Deviation 222.35 |
| Placebo | Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline | 266.2 mL | Standard Deviation 191.41 |
| Placebo | Change From Baseline in Maximum Cystometric Capacity (MCC) | Change from Baseline at Week 6 (n=12,13,11) | -64.5 mL | Standard Deviation 136.98 |
Secondary
Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP)
MDP was measured at the first involuntary detrusor contraction using urodynamic testing. A catheter was inserted into the bladder at Baseline and Week 6 and the pressure \[measured in centimeters water (cm H20)\] was determined as the bladder filled. A negative change from Baseline indicated improvement (less Detrusor pressure).
Time frame: Baseline, Week 6
Population: Intent-to-treat population included all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A 200U | Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) | Baseline | 39.1 cm H2O | Standard Deviation 30.45 |
| Botulinum Toxin Type A 200U | Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) | Change from Baseline at Week 6 (n=4,9,9) | -23.3 cm H2O | Standard Deviation 28.96 |
| Botulinum Toxin Type A 300U | Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) | Baseline | 42.6 cm H2O | Standard Deviation 22.65 |
| Botulinum Toxin Type A 300U | Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) | Change from Baseline at Week 6 (n=4,9,9) | 0.3 cm H2O | Standard Deviation 32.67 |
| Placebo | Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) | Baseline | 41.9 cm H2O | Standard Deviation 18.91 |
| Placebo | Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) | Change from Baseline at Week 6 (n=4,9,9) | 8.7 cm H2O | Standard Deviation 23.91 |
Secondary
Change From Baseline in the Number of Urinary Incontinence Episodes
The number of urinary incontinence episodes or leakage occurring over the previous 3 days was recorded in the patient bladder diary at Baseline and prior to Week 6. A negative change from Baseline indicated improvement (less incontinence/leakage).
Time frame: Baseline, Week 6
Population: Participants from the Intent-to-treat population (all randomized participants) using observed data for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A 200U | Change From Baseline in the Number of Urinary Incontinence Episodes | Baseline | 12.5 Episodes | Standard Deviation 9.78 |
| Botulinum Toxin Type A 200U | Change From Baseline in the Number of Urinary Incontinence Episodes | Change from Baseline at Week 6 (n=13,11,11) | -10.2 Episodes | Standard Deviation 7.7 |
| Botulinum Toxin Type A 300U | Change From Baseline in the Number of Urinary Incontinence Episodes | Baseline | 13.5 Episodes | Standard Deviation 6.48 |
| Botulinum Toxin Type A 300U | Change From Baseline in the Number of Urinary Incontinence Episodes | Change from Baseline at Week 6 (n=13,11,11) | -9.5 Episodes | Standard Deviation 6.96 |
| Placebo | Change From Baseline in the Number of Urinary Incontinence Episodes | Baseline | 9.3 Episodes | Standard Deviation 6.59 |
| Placebo | Change From Baseline in the Number of Urinary Incontinence Episodes | Change from Baseline at Week 6 (n=13,11,11) | -3.4 Episodes | Standard Deviation 4.57 |
Other Pre-specified
Number of Participants With at Least a 15% Decrease From Baseline in FVC
Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible at Baseline, Weeks 2, 6 and 12.
Time frame: Baseline, Weeks 2, 6 and 12
Population: Safety population included all randomized participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Botulinum Toxin Type A 200U | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 6 (n=15,14,12) | 2 Participants |
| Botulinum Toxin Type A 200U | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 2 (n=15,14,12) | 0 Participants |
| Botulinum Toxin Type A 200U | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 12 (n=14,12,9) | 0 Participants |
| Botulinum Toxin Type A 300U | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 6 (n=15,14,12) | 1 Participants |
| Botulinum Toxin Type A 300U | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 2 (n=15,14,12) | 1 Participants |
| Botulinum Toxin Type A 300U | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 12 (n=14,12,9) | 1 Participants |
| Placebo | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 2 (n=15,14,12) | 1 Participants |
| Placebo | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 12 (n=14,12,9) | 0 Participants |
| Placebo | Number of Participants With at Least a 15% Decrease From Baseline in FVC | Week 6 (n=15,14,12) | 0 Participants |
Other Pre-specified
Number of Participants With at Least a 20% Decrease From Baseline in FVC
Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible at Baseline, Weeks 2, 6 and 12.
Time frame: Baseline, Weeks 2, 6 and 12
Population: Safety population included all randomized participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Botulinum Toxin Type A 200U | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 6 (n=15,14,12) | 1 Participants |
| Botulinum Toxin Type A 200U | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 2 (n=15,14,12) | 0 Participants |
| Botulinum Toxin Type A 200U | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 12 (n=14,12,9) | 0 Participants |
| Botulinum Toxin Type A 300U | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 6 (n=15,14,12) | 0 Participants |
| Botulinum Toxin Type A 300U | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 2 (n=15,14,12) | 1 Participants |
| Botulinum Toxin Type A 300U | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 12 (n=14,12,9) | 1 Participants |
| Placebo | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 2 (n=15,14,12) | 0 Participants |
| Placebo | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 12 (n=14,12,9) | 0 Participants |
| Placebo | Number of Participants With at Least a 20% Decrease From Baseline in FVC | Week 6 (n=15,14,12) | 0 Participants |