Overactive Bladder
Conditions
Brief summary
The purpose of this study is to assess the safety and effectiveness of botulinum toxin type A in treating overactive bladder in spinal cord injury or multiple sclerosis patients
Interventions
BIOLOGICALbotulinum toxin Type A (200U)
botulinum toxin Type A 200 U injection at Day 1 followed by botulinum toxin Type A 200 U injection \> Week 12; injections into detrusor
BIOLOGICALbotulinum toxin Type A (300U)
botulinum toxin Type A 300 U injection on Day 1 followed by botulinum toxin Type A 300 U injection \> Week 12; injections into detrusor
Placebo injection on Day 1 followed by botulinum toxin Type A 200 U injection \> 12 weeks; injections into detrusor
Placebo injection on Day 1 followed by botulinum toxin Type A 300 U injection \> Week 12; injections into 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
Exclusion criteria
* History or evidence of pelvic or urologic abnormality * Previous or current diagnosis of bladder or prostate cancer * Urinary tract infection at time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Number of Weekly Episodes of Urinary Incontinence | Baseline, Week 6 | Change from baseline in the weekly frequency of incontinence episodes at Week 6 after the first treatment. Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. A negative number change from baseline indicates a reduction in incontinence episodes (improvement). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline, Week 6 | Change from baseline in MCC at Week 6. MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in maximum volume of urine the bladder holds. |
| Change From Baseline in Maximum Detrusor Pressure (MDP) | Baseline, Week 6 | Change from baseline in MDP during the first involuntary detrusor contraction at week 6. MDP represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. The greater the negative number change from baseline, the better the improvement. |
| Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire | Baseline, Week 6 | Change from baseline in I-QOL questionnaire total score at Week 6, as completed by the patient. The I-QOL is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL, and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0=worst QOL and 100=best QOL). A positive change from baseline represents an improvement. |
Countries
Brazil, Canada, France, Italy, Netherlands, Portugal, Singapore, South Africa, Spain, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin Type A (300U) botulinum toxin Type A (300U) | 91 |
| Botulinum Toxin Type A (200U) botulinum toxin Type A (200U) | 92 |
| Placebo Normal saline (placebo) | 92 |
| Total | 275 |
Baseline characteristics
| Characteristic | Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo | Total |
|---|---|---|---|---|
| Age, Customized < 40 years | 30 participants | 31 participants | 25 participants | 86 participants |
| Age, Customized >= 75 years | 1 participants | 1 participants | 1 participants | 3 participants |
| Age, Customized Between 40 and 64 years | 56 participants | 55 participants | 61 participants | 172 participants |
| Age, Customized Between 65 and 74 years | 4 participants | 5 participants | 5 participants | 14 participants |
| Sex: Female, Male Female | 52 Participants | 54 Participants | 49 Participants | 155 Participants |
| Sex: Female, Male Male | 39 Participants | 38 Participants | 43 Participants | 120 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 | 70 / 89 | 63 / 91 | 52 / 90 |
| serious Total, serious adverse events | 18 / 89 | 17 / 91 | 23 / 90 |
Outcome results
Primary
Change From Baseline in Number of Weekly Episodes of Urinary Incontinence
Change from baseline in the weekly frequency of incontinence episodes at Week 6 after the first treatment. Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).
Time frame: Baseline, Week 6
Population: Intent-To-Treat, defined as all patients who started the study (randomized)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A (300U) | Change From Baseline in Number of Weekly Episodes of Urinary Incontinence | Baseline | 31.2 Number of Weekly Episodes | Standard Deviation 18.14 |
| Botulinum Toxin Type A (300U) | Change From Baseline in Number of Weekly Episodes of Urinary Incontinence | Week 6 | -19.4 Number of Weekly Episodes | Standard Deviation 25.67 |
| Botulinum Toxin Type A (200U) | Change From Baseline in Number of Weekly Episodes of Urinary Incontinence | Baseline | 32.5 Number of Weekly Episodes | Standard Deviation 18.44 |
| Botulinum Toxin Type A (200U) | Change From Baseline in Number of Weekly Episodes of Urinary Incontinence | Week 6 | -21.8 Number of Weekly Episodes | Standard Deviation 18.06 |
| Placebo | Change From Baseline in Number of Weekly Episodes of Urinary Incontinence | Baseline | 36.7 Number of Weekly Episodes | Standard Deviation 30.67 |
| Placebo | Change From Baseline in Number of Weekly Episodes of Urinary Incontinence | Week 6 | -13.2 Number of Weekly Episodes | Standard Deviation 20.02 |
Secondary
Change From Baseline in Maximum Cystometric Capacity (MCC)
Change from baseline in MCC at Week 6. MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in maximum volume of urine the bladder holds.
Time frame: Baseline, Week 6
Population: Intent-To-Treat, defined as all patients who started the study (randomized)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A (300U) | Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline | 246.8 Milliliters (mL) of urine | Standard Deviation 149.06 |
| Botulinum Toxin Type A (300U) | Change From Baseline in Maximum Cystometric Capacity (MCC) | Week 6 | 157.2 Milliliters (mL) of urine | Standard Deviation 185.18 |
| Botulinum Toxin Type A (200U) | Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline | 247.3 Milliliters (mL) of urine | Standard Deviation 147.61 |
| Botulinum Toxin Type A (200U) | Change From Baseline in Maximum Cystometric Capacity (MCC) | Week 6 | 157.0 Milliliters (mL) of urine | Standard Deviation 164.75 |
| Placebo | Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline | 249.4 Milliliters (mL) of urine | Standard Deviation 139.29 |
| Placebo | Change From Baseline in Maximum Cystometric Capacity (MCC) | Week 6 | 6.5 Milliliters (mL) of urine | Standard Deviation 144.77 |
Secondary
Change From Baseline in Maximum Detrusor Pressure (MDP)
Change from baseline in MDP during the first involuntary detrusor contraction at week 6. MDP represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. The greater the negative number change from baseline, the better the improvement.
Time frame: Baseline, Week 6
Population: Intent-To-Treat, defined as all patients who started the study (randomized)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A (300U) | Change From Baseline in Maximum Detrusor Pressure (MDP) | Week 6 | -26.9 Centimeters of water (cm H2O) | Standard Deviation 33.17 |
| Botulinum Toxin Type A (300U) | Change From Baseline in Maximum Detrusor Pressure (MDP) | Baseline | 42.1 Centimeters of water (cm H2O) | Standard Deviation 33.21 |
| Botulinum Toxin Type A (200U) | Change From Baseline in Maximum Detrusor Pressure (MDP) | Baseline | 51.7 Centimeters of water (cm H2O) | Standard Deviation 40.95 |
| Botulinum Toxin Type A (200U) | Change From Baseline in Maximum Detrusor Pressure (MDP) | Week 6 | -28.5 Centimeters of water (cm H2O) | Standard Deviation 47.82 |
| Placebo | Change From Baseline in Maximum Detrusor Pressure (MDP) | Baseline | 41.5 Centimeters of water (cm H2O) | Standard Deviation 31.17 |
| Placebo | Change From Baseline in Maximum Detrusor Pressure (MDP) | Week 6 | 6.4 Centimeters of water (cm H2O) | Standard Deviation 41.1 |
Secondary
Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire
Change from baseline in I-QOL questionnaire total score at Week 6, as completed by the patient. The I-QOL is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL, and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0=worst QOL and 100=best QOL). A positive change from baseline represents an improvement.
Time frame: Baseline, Week 6
Population: Intent-To-Treat, defined as all patients who started the study (randomized)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A (300U) | Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire | Baseline | 36.32 Number on a Scale (Score) | Standard Deviation 18.685 |
| Botulinum Toxin Type A (300U) | Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire | Week 6 | 24.26 Number on a Scale (Score) | Standard Deviation 28.981 |
| Botulinum Toxin Type A (200U) | Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire | Baseline | 37.46 Number on a Scale (Score) | Standard Deviation 20.109 |
| Botulinum Toxin Type A (200U) | Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire | Week 6 | 24.43 Number on a Scale (Score) | Standard Deviation 25.372 |
| Placebo | Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire | Baseline | 35.72 Number on a Scale (Score) | Standard Deviation 18.656 |
| Placebo | Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire | Week 6 | 11.71 Number on a Scale (Score) | Standard Deviation 20.163 |