Urinary Bladder, Overactive, Urinary Incontinence
Conditions
Brief summary
This study will evaluate the efficacy and safety of onabotulinumtoxinA 100 U (BOTOX®), compared to placebo, when injected into the bladder using an alternative injection paradigm in reducing the number of daily urinary incontinence episodes in patients with overactive bladder (OAB) and urinary incontinence whose symptoms have not been adequately managed with an anticholinergic.
Interventions
BIOLOGICALonabotulinumtoxinA
OnabotulinumtoxinA (BOTOX®) injection into the bladder.
DRUGPlacebo (saline)
Placebo (saline) injection into the bladder.
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
* Participant weighs ≥ 40 kg (88 lb) * Participant has symptoms of Over Active Bladder (OAB) (frequency and urgency) with urinary incontinence for a period of at least 6 months immediately prior to screening.
Exclusion criteria
* Participant has symptoms of OAB due to any known neurological reason (eg, spinal cord injury, multiple sclerosis, cerebrovascular accident, Alzheimer's disease, Parkinson's disease, etc.) * Participant has received pharmacologic therapy to treat symptoms of OAB, including nocturia, within 7 days of the start of the screening period procedures * Participant uses clean intermittent catheterization (CIC) or indwelling catheter to manage urinary incontinence * Participant has been treated with any intravesical pharmacologic agent (eg, capsaicin, resiniferatoxin) within 12 months of Day 1 * Participant has had previous or current botulinum toxin therapy of any serotype for any urological condition * Participant has had previous or current botulinum toxin therapy of any serotype for any non-urological condition within 12 weeks of Day 1 * Participant has been immunized for any botulinum toxin serotype * Participant has history or evidence of any pelvic or urological abnormalities, bladder surgery or disease, other than OAB, that may affect bladder function * Participant has an active genital infection, other than genital warts, either concurrently or within 4 weeks prior to screening * Participant has a history or current diagnosis of bladder cancer or other urothelial malignancy * Participant is male with previous or current diagnosis of prostate cancer * Participant has a history of 2 or more urinary tract infections (UTIs) within 6 months of Day 1 or is taking prophylactic antibiotics to prevent chronic UTIs * Participant has current or previous uninvestigated hematuria * Participant has hemophilia, or other clotting factor deficiencies, or disorders that cause bleeding diathesis * Participant cannot withhold any antiplatelet, anticoagulant therapy or medications with anticoagulant effects for 3 days prior to Day 1 * Participant has a known allergy or sensitivity to any botulinum toxin preparation * Participant has any medical condition that may put him/her at increased risk with exposure to BOTOX® including diagnosed myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis * Participant has current swallowing or breathing difficulties.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daily Average Number of Urinary Incontinence Episodes | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12 | The participant recorded urinary incontinence in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An analysis of covariance (ANCOVA) model with treatment as a factor at 2 levels, and the number of Urgency Urinary Incontinence (UUI) episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of episodes of incontinence as covariates was used for analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Complete Continence | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12] | Complete continence is defined as 100% reduction in urinary incontinence from Baseline. |
| Change From Baseline in Daily Average Number of Nocturia Episodes | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to, 3 consecutive days prior to Week 12 | The participants recorded the number of nocturia episodes in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of nocturia episodes as covariates was used for analyses. |
| Change From Baseline in Daily Average Number of Micturition Episodes | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12 | The participant recorded the number of micturition episodes in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of micturition as covariates was used for analyses. |
| Change From Baseline in Daily Average Number of Urgency Episodes | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12 | The participant recorded the number of urgency episode in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of urgency episodes as covariates was used for analyses. |
| Percentage of Participants Who Have a Positive Treatment Response on the Treatment Benefit Scale (TBS) | Week 12 | The participant rated their condition during treatment using the TBS 4-point scale where: 1=greatly improved, 2=improved, 3=not changed or 4=worsened. A positive treatment response is either as score of 1=greatly improved or 2=improved. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BOTOX® 100 U/BOTOX® 100 U BOTOX® (onabotulinumtoxinA) 100 U injection into the bladder on Day 1 in the Double-Blind Treatment Period and a second injection BOTOX® 100 U after Week 12 if applicable in the Open-Label Re-Treatment Period. | 80 |
| Placebo/BOTOX® 100 U Placebo (saline) injection into the bladder on Day 1 in the Double-Blind Treatment Period and a second injection BOTOX® 100 U after Week 12 if applicable in the Open-Label Re-Treatment Period. | 40 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment Period | Adverse Event | 2 | 0 |
| Double-Blind Treatment Period | Lack of Efficacy | 1 | 0 |
| Double-Blind Treatment Period | Protocol Violation | 2 | 1 |
| Double-Blind Treatment Period | Reason not Specified | 2 | 1 |
| Double-Blind Treatment Period | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | BOTOX® 100 U/BOTOX® 100 U | Placebo/BOTOX® 100 U | Total |
|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 11.91 | 61.9 years STANDARD_DEVIATION 11.26 | 61.0 years STANDARD_DEVIATION 11.67 |
| Daily Average Number of Urinary Incontinence Episodes | 6.31 incontinence episodes per day STANDARD_DEVIATION 4.341 | 6.34 incontinence episodes per day STANDARD_DEVIATION 3.061 | 6.32 incontinence episodes per day STANDARD_DEVIATION 3.947 |
| Race/Ethnicity, Customized Asian | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 9 Participants | 1 Participants | 10 Participants |
| Race/Ethnicity, Customized Caucasian | 65 Participants | 39 Participants | 104 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 75 Participants | 38 Participants | 113 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Female | 75 Participants | 40 Participants | 115 Participants |
| Sex: Female, Male Male | 5 Participants | 0 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 40 | 0 / 58 | 0 / 33 |
| other Total, other adverse events | 31 / 78 | 13 / 39 | 14 / 58 | 16 / 33 |
| serious Total, serious adverse events | 5 / 78 | 2 / 39 | 2 / 58 | 1 / 33 |
Outcome results
Primary
Change From Baseline in Daily Average Number of Urinary Incontinence Episodes
The participant recorded urinary incontinence in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An analysis of covariance (ANCOVA) model with treatment as a factor at 2 levels, and the number of Urgency Urinary Incontinence (UUI) episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of episodes of incontinence as covariates was used for analyses.
Time frame: Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12
Population: Modified Intent-to-treat (mITT) Population included all randomized participants who had at least one efficacy assessment at Baseline and a postbaseline visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® 100 U/BOTOX® 100 U | Change From Baseline in Daily Average Number of Urinary Incontinence Episodes | -2.99 incontinence episodes per day | Standard Error 0.488 |
| Placebo/BOTOX® 100 U | Change From Baseline in Daily Average Number of Urinary Incontinence Episodes | -0.42 incontinence episodes per day | Standard Error 0.612 |
p-value: <0.000195% CI: [-3.68, -1.46]ANCOVA
Secondary
Change From Baseline in Daily Average Number of Micturition Episodes
The participant recorded the number of micturition episodes in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of micturition as covariates was used for analyses.
Time frame: Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12
Population: mITT Population included all randomized participants who had at least one efficacy assessment at Baseline and a postbaseline visit. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® 100 U/BOTOX® 100 U | Change From Baseline in Daily Average Number of Micturition Episodes | -2.25 micturition episodes per day | Standard Error 0.421 |
| Placebo/BOTOX® 100 U | Change From Baseline in Daily Average Number of Micturition Episodes | -0.01 micturition episodes per day | Standard Error 0.525 |
p-value: <0.000195% CI: [-3.3, -1.18]ANCOVA
Secondary
Change From Baseline in Daily Average Number of Nocturia Episodes
The participants recorded the number of nocturia episodes in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of nocturia episodes as covariates was used for analyses.
Time frame: Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to, 3 consecutive days prior to Week 12
Population: mITT Population included all randomized participants who had at least one efficacy assessment at Baseline and a postbaseline visit. Number analyzed is the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® 100 U/BOTOX® 100 U | Change From Baseline in Daily Average Number of Nocturia Episodes | -0.53 nocturia episodes per day | Standard Error 0.154 |
| Placebo/BOTOX® 100 U | Change From Baseline in Daily Average Number of Nocturia Episodes | 0.17 nocturia episodes per day | Standard Error 0.193 |
p-value: 0.000495% CI: [-1.09, -0.32]ANCOVA
Secondary
Change From Baseline in Daily Average Number of Urgency Episodes
The participant recorded the number of urgency episode in a 3-day bladder diary. Data for the three days was averaged. A negative change from Baseline indicates improvement. An ANCOVA model with treatment as a factor at 2 levels, and the number of UUI episodes reported at Baseline (\<= 9 versus \> 9 daily episodes) and Baseline daily average number of urgency episodes as covariates was used for analyses.
Time frame: Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12
Population: mITT Population included all randomized participants who had at least one efficacy assessment at Baseline and a postbaseline visit. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® 100 U/BOTOX® 100 U | Change From Baseline in Daily Average Number of Urgency Episodes | -2.79 urgency episodes per day | Standard Error 0.491 |
| Placebo/BOTOX® 100 U | Change From Baseline in Daily Average Number of Urgency Episodes | -0.23 urgency episodes per day | Standard Error 0.618 |
p-value: <0.000195% CI: [-3.73, -1.39]ANCOVA
Secondary
Percentage of Participants Who Achieved Complete Continence
Complete continence is defined as 100% reduction in urinary incontinence from Baseline.
Time frame: Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12]
Population: mITT Population included all randomized participants who had at least one efficacy assessment at Baseline and a postbaseline visit. Number analyzed is the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOTOX® 100 U/BOTOX® 100 U | Percentage of Participants Who Achieved Complete Continence | 13.9 percentage of participants |
| Placebo/BOTOX® 100 U | Percentage of Participants Who Achieved Complete Continence | 2.7 percentage of participants |
95% CI: [0.75, 50.37]
Secondary
Percentage of Participants Who Have a Positive Treatment Response on the Treatment Benefit Scale (TBS)
The participant rated their condition during treatment using the TBS 4-point scale where: 1=greatly improved, 2=improved, 3=not changed or 4=worsened. A positive treatment response is either as score of 1=greatly improved or 2=improved.
Time frame: Week 12
Population: mITT Population included all randomized participants who had at least one efficacy assessment at Baseline and a postbaseline visit. Number analyzed is the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOTOX® 100 U/BOTOX® 100 U | Percentage of Participants Who Have a Positive Treatment Response on the Treatment Benefit Scale (TBS) | 74.0 percentage of participants |
| Placebo/BOTOX® 100 U | Percentage of Participants Who Have a Positive Treatment Response on the Treatment Benefit Scale (TBS) | 17.6 percentage of participants |
95% CI: [3.23, 52.57]