Overactive Bladder
Conditions
Brief summary
This is a study to evaluate the efficacy and safety of onabotulinumtoxinA (BOTOX®) compared with placebo, in achieving a 100% reduction in urinary incontinence in patients with overactive bladder (OAB) not properly managed with an anticholinergic.
Interventions
BIOLOGICALonabotulinumtoxinA
OnabotulinumtoxinA (BOTOX®) injected into the detrusor.
DRUGNormal saline
Normal saline (placebo) injected into the detrusor.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
-Patients with symptoms of Overactive Bladder (OAB) (frequency and urgency) with urinary incontinence for at least 6 months prior to screening.
Exclusion criteria
* Symptoms of OAB due to a neurological reason * Use of anticholinergics or other medications or therapies to treat symptoms of OAB within 7 days of screening * Use of Clean Intermittent Catheterization (CIC) or indwelling catheter to manage urinary incontinence * Use of botulinum toxin therapy of any serotype for any urological condition * Use of botulinum toxin therapy of any serotype for any non-urological condition in the 12 weeks prior to screening * History of any pelvic or urological abnormalities, bladder surgery or disease, other than OAB, that may affect bladder function * Diagnosis of Myasthenia gravis, Eaton-Lambert syndrome, or Amyotrophic Lateral Sclerosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve a 100% Reduction in Urinary Incontinence Episodes | Baseline, Week 12 | Urinary incontinence is defined as involuntary loss of urine as recorded by the participant in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of incontinence episodes were averaged daily during this period and compared to baseline to determine 100% reduction in episodes. |
| Change From Baseline in the Daily Average Number of Episodes of Urinary Incontinence | Baseline, Week 12 | Urinary incontinence is defined as involuntary loss of urine as recorded by the participant in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of incontinence episodes were averaged daily during this period. A negative number change from Baseline indicates an improvement and a positive number change from Baseline indicates a worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Baseline, Week 12 | The King's Health Questionnaire is a disease-specific questionnaire that measures the quality of life of participants with urinary incontinence. The questionnaire consists of 7 domains, including emotions, personal relationships, physical limitations, role limitations, severity (coping) measures, sleep/energy and social limitations. Domain scores range from 0 to 100, with a lower score indicating a preferable health status (absence of urinary incontinence impacts). A negative number change from Baseline indicates improvement and a positive number change from Baseline indicates a worsening. |
| Change From Baseline in the Daily Average Number of Micturition Episodes | Baseline, Week 12 | The number of micturition episodes (the number of times a patient urinates into the toilet) in Treatment Cycle 1 was recorded by the participant in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of micturition episodes were averaged daily during this period A negative number change from Baseline indicates an improvement and a positive number change from Baseline indicates a worsening. |
| Change From Baseline in the Daily Average Number of Urgency Episodes | Baseline, Week 12 | The number of daily urgency episodes (the number of times a patient experiences the urgency to urinate) in Treatment Cycle 1 was recorded by the patient in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of urgency episodes were averaged daily during this period A negative number change from Baseline indicates an improvement and a positive number change from Baseline indicates a worsening. |
| Change From Baseline in the Daily Average Number of Nocturia Episodes | Baseline, Week 12 | Nocturia episodes were recorded by the participant in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of nocturia episodes were averaged daily during this period. A nocturia episode is a void (urinating into the toilet) that interrupts one's sleep. A negative number change from Baseline indicates an improvement and a positive number change from baseline indicates a worsening. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OnabotulinumtoxinA OnabotulinumtoxinA (BOTOX®) 100U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100U after a minimum of 12 weeks (if applicable). | 129 |
| Placebo/OnabotulinumtoxinA Placebo (Normal saline) injected into the detrusor on Day 1, followed by an injection of onabotulinumtoxinA 100U after a minimum of 12 weeks (if applicable). | 125 |
| Total | 254 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Cycle 1 | Adverse Event | 2 | 0 |
| Cycle 1 | Lost to Follow-up | 4 | 0 |
| Cycle 1 | Other Miscellaneous Reasons | 3 | 1 |
| Cycle 1 | Personal Reasons | 4 | 2 |
| Cycle 1 | Protocol Violation | 0 | 1 |
| Cycle 2 | Adverse Event | 1 | 0 |
| Cycle 2 | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | OnabotulinumtoxinA | Placebo/OnabotulinumtoxinA | Total |
|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 12.73 | 60.9 years STANDARD_DEVIATION 12.1 | 60.8 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 114 Participants | 112 Participants | 226 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 28 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 | 51 / 128 | 34 / 125 | 75 / 195 |
| serious Total, serious adverse events | 6 / 128 | 8 / 125 | 3 / 195 |
Outcome results
Primary
Change From Baseline in the Daily Average Number of Episodes of Urinary Incontinence
Urinary incontinence is defined as involuntary loss of urine as recorded by the participant in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of incontinence episodes were averaged daily during this period. A negative number change from Baseline indicates an improvement and a positive number change from Baseline indicates a worsening.
Time frame: Baseline, Week 12
Population: Participants from the Intent-to-Treat Population, all participants who were randomized to study drug, with data available at Baseline and Week 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Episodes of Urinary Incontinence | Baseline | 5.4 incontinence episodes | Standard Deviation 3.16 |
| OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Episodes of Urinary Incontinence | Change at Week 12 | -3.4 incontinence episodes | Standard Deviation 3.69 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Episodes of Urinary Incontinence | Baseline | 5.9 incontinence episodes | Standard Deviation 3.75 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Episodes of Urinary Incontinence | Change at Week 12 | -1.7 incontinence episodes | Standard Deviation 3.23 |
Primary
Percentage of Participants Who Achieve a 100% Reduction in Urinary Incontinence Episodes
Urinary incontinence is defined as involuntary loss of urine as recorded by the participant in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of incontinence episodes were averaged daily during this period and compared to baseline to determine 100% reduction in episodes.
Time frame: Baseline, Week 12
Population: Participants from the Intent-to-Treat Population, all participants who were randomized to study drug, with data available at Baseline and Week 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OnabotulinumtoxinA | Percentage of Participants Who Achieve a 100% Reduction in Urinary Incontinence Episodes | 32.0 percentage of participants |
| Placebo/OnabotulinumtoxinA | Percentage of Participants Who Achieve a 100% Reduction in Urinary Incontinence Episodes | 7.2 percentage of participants |
Secondary
Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores
The King's Health Questionnaire is a disease-specific questionnaire that measures the quality of life of participants with urinary incontinence. The questionnaire consists of 7 domains, including emotions, personal relationships, physical limitations, role limitations, severity (coping) measures, sleep/energy and social limitations. Domain scores range from 0 to 100, with a lower score indicating a preferable health status (absence of urinary incontinence impacts). A negative number change from Baseline indicates improvement and a positive number change from Baseline indicates a worsening.
Time frame: Baseline, Week 12
Population: Intent-to-Treat Population included all participants who were randomized to study drug, n is the number of participants with available data at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Emotions, Baseline (n=128,123) | 52.38 score on a scale | Standard Deviation 30.982 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Emotions, Change at Week 12 (n=121,118) | -21.98 score on a scale | Standard Deviation 33.164 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Personal Relationships, Baseline (n=87,86) | 42.91 score on a scale | Standard Deviation 35 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Personal Relationships,Change at Week 12 (n=71,74) | -18.31 score on a scale | Standard Deviation 31.39 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Physical Limitations, Baseline (n=128,125) | 66.41 score on a scale | Standard Deviation 29.651 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Physical Limitations,Change at Week 12 (n=121,120) | -32.37 score on a scale | Standard Deviation 35.046 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Role Limitations, Baseline (n=127,123) | 70.73 score on a scale | Standard Deviation 27.516 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Role Limitations, Change at Week 12 (n=117,117) | -37.75 score on a scale | Standard Deviation 32.928 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Severity (Coping) Measures, Baseline (n=128,124) | 65.68 score on a scale | Standard Deviation 21.347 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Severity (Coping), Change at Week 12 (n=121,119) | -24.89 score on a scale | Standard Deviation 29.558 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Sleep/Energy, Baseline (n=128,123) | 71.35 score on a scale | Standard Deviation 25.696 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Sleep/Energy, Change at Week 12 (n=121,118) | -24.93 score on a scale | Standard Deviation 26.885 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Social Limitations, Baseline (n=128,125) | 43.69 score on a scale | Standard Deviation 28.911 |
| OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Social Limitations, Change at Week 12 (n=120,120) | -20.40 score on a scale | Standard Deviation 32.634 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Sleep/Energy, Baseline (n=128,123) | 71.00 score on a scale | Standard Deviation 25.053 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Emotions, Baseline (n=128,123) | 53.60 score on a scale | Standard Deviation 29.243 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Role Limitations, Change at Week 12 (n=117,117) | -16.67 score on a scale | Standard Deviation 28.196 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Emotions, Change at Week 12 (n=121,118) | -6.63 score on a scale | Standard Deviation 26.177 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Social Limitations, Baseline (n=128,125) | 46.81 score on a scale | Standard Deviation 32.065 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Personal Relationships, Baseline (n=87,86) | 43.22 score on a scale | Standard Deviation 36.638 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Severity (Coping) Measures, Baseline (n=128,124) | 69.18 score on a scale | Standard Deviation 22.201 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Personal Relationships,Change at Week 12 (n=71,74) | -6.98 score on a scale | Standard Deviation 28.537 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Sleep/Energy, Change at Week 12 (n=121,118) | -10.03 score on a scale | Standard Deviation 25.796 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Physical Limitations, Baseline (n=128,125) | 64.93 score on a scale | Standard Deviation 30.145 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Severity (Coping), Change at Week 12 (n=121,119) | -9.17 score on a scale | Standard Deviation 19.925 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Physical Limitations,Change at Week 12 (n=121,120) | -10.00 score on a scale | Standard Deviation 28.039 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Social Limitations, Change at Week 12 (n=120,120) | -5.97 score on a scale | Standard Deviation 25.332 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in King's Health Questionnaire (KHQ) Domain Scores | Role Limitations, Baseline (n=127,123) | 71.95 score on a scale | Standard Deviation 29.362 |
Secondary
Change From Baseline in the Daily Average Number of Micturition Episodes
The number of micturition episodes (the number of times a patient urinates into the toilet) in Treatment Cycle 1 was recorded by the participant in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of micturition episodes were averaged daily during this period A negative number change from Baseline indicates an improvement and a positive number change from Baseline indicates a worsening.
Time frame: Baseline, Week 12
Population: Participants from the Intent-to-Treat Population, all participants who were randomized to study drug, with data available at Baseline and Week 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Micturition Episodes | Baseline | 10.2 micturition episodes | Standard Deviation 2.99 |
| OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Micturition Episodes | Change at Week 12 | -2.6 micturition episodes | Standard Deviation 2.71 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Micturition Episodes | Baseline | 11.1 micturition episodes | Standard Deviation 3.43 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Micturition Episodes | Change at Week 12 | -1.3 micturition episodes | Standard Deviation 2.62 |
Secondary
Change From Baseline in the Daily Average Number of Nocturia Episodes
Nocturia episodes were recorded by the participant in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of nocturia episodes were averaged daily during this period. A nocturia episode is a void (urinating into the toilet) that interrupts one's sleep. A negative number change from Baseline indicates an improvement and a positive number change from baseline indicates a worsening.
Time frame: Baseline, Week 12
Population: Participants from the Intent-to-Treat Population, all participants who were randomized to study drug, with data available at Baseline and Week 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Nocturia Episodes | Baseline | 2.2 nocturia episodes | Standard Deviation 1.43 |
| OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Nocturia Episodes | Change at Week 12 | -0.7 nocturia episodes | Standard Deviation 1.34 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Nocturia Episodes | Change at Week 12 | -0.4 nocturia episodes | Standard Deviation 1.28 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Nocturia Episodes | Baseline | 2.1 nocturia episodes | Standard Deviation 1.43 |
Secondary
Change From Baseline in the Daily Average Number of Urgency Episodes
The number of daily urgency episodes (the number of times a patient experiences the urgency to urinate) in Treatment Cycle 1 was recorded by the patient in a bladder diary during the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of urgency episodes were averaged daily during this period A negative number change from Baseline indicates an improvement and a positive number change from Baseline indicates a worsening.
Time frame: Baseline, Week 12
Population: Participants from the Intent-to-Treat Population, all participants who were randomized to study drug, with data available at Baseline and Week 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Urgency Episodes | Baseline | 4.9 urgency episodes | Standard Deviation 3.09 |
| OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Urgency Episodes | Change at Week 12 | -3.3 urgency episodes | Standard Deviation 3.49 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Urgency Episodes | Baseline | 5.3 urgency episodes | Standard Deviation 3.47 |
| Placebo/OnabotulinumtoxinA | Change From Baseline in the Daily Average Number of Urgency Episodes | Change at Week 12 | -1.7 urgency episodes | Standard Deviation 3.24 |