Urinary Incontinence, Urinary Bladder, Overactive
Conditions
Brief summary
This was a multicenter, randomized, double-blind, parallel-group, multiple-dose study to evaluate the efficacy and safety of BOTOX in adolescents with urinary incontinence due to overactive bladder (OAB) with inadequate management with anticholinergic therapy. Participants were randomized in a 1:1:1 ratio to receive a single Tx of 25 U, 50 U, or 100 U BOTOX (not to exceed 6 U/kg) on Day 1, were seen after each treatment at Weeks 2, 6, and 12 post-treatment, and thereafter at alternating telephone and clinic visits every 6 weeks until they qualified for further retreatment/exited the study. Participants could receive multiple treatments dependent upon the number and timing of patient requests/qualification for retreatment. At each retreatment the investigator could keep the dose the same or increase it one dose level in a blinded fashion. Participants exited the study once 96 weeks have elapsed since entry on Day 1 and at least 12 weeks follow-up since their last study treatment had occurred.
Interventions
BIOLOGICALBOTOX®
Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Symptoms of overactive bladder (OAB) (frequency/urgency) with urinary incontinence for at least 6 months * OAB symptoms not adequately managed by 1 or more anticholinergic agents
Exclusion criteria
* OAB caused by a neurological condition * Use of anticholinergics or other medications to treat OAB symptoms within 7 days * Current use of indwelling catheter or clean intermittent catheterization to empty the bladder * Previous or current use of botulinum toxin therapy of any serotype for any urological condition, or treatment with botulinum toxin of any serotype within 3 months for any other condition or use * Myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1 | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition Episodes | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | Micturition was defined as toilet voids recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime micturition episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. |
| Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency Episodes | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | Participants recorded daytime urgency episodes in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime urgency episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. |
| Percentage of Participants With Night Time Urinary Incontinence | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | Urinary incontinence was defined as involuntary loss of urine. Participants recorded night time urinary incontinence episodes in a bladder diary during 2 consecutive days in the week prior to the study visit. Night time is defined as the time between going to bed to sleep for the night and waking up to start the next day. The number of daily night time urinary incontinence episodes were averaged during the 2-day period. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. |
| Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL) | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | The volume per micturition was derived from the total urine volume voided over 1 daytime period during the 2-day bladder diary collection period divided by the number of voids in the same daytime period. Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. |
| Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ) | From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1 | The PinQ is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time) and a total sum score is calculated (from 0 to 80), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement. |
| Change From Study Baseline in PinQ Item 'My Bladder Problem Makes me Feel Bad About Myself | From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1 | The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement. |
| Change From Study Baseline in PinQ Item 'I Miss Out on Being With Friends Because of my Bladder Problems | From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1 | The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement. |
| Percentage of Participants With a Positive Treatment Response in the Modified Treatment Benefit Scale | At Week 12 in Treatment Cycle 1 | The Modified Treatment Benefit Scale (Modified TBS) is a single-item scale designed to assess the change in the participant's overactive bladder (OAB) condition following treatment. The participant's current condition (urinary problems, urinary incontinence) is compared to their condition prior to receipt of any study treatment by selection of greatly improved, improved, not changed or worsened. Participants who selected greatly improved or improved were considered to have a positive treatment response. |
| Time to Participant's First Request for Retreatment | From the day of BOTOX treatment in Treatment Cycle 1 to the request for subsequent treatment | The time from the day of BOTOX treatment to the request for the subsequent treatment was estimated using a Kaplan-Meier survival method for each treatment group. Participants who did not request retreatment were treated as censored at the time of their last study visit or study exit. |
| Time to Participant's Qualification for Retreatment | From the day of BOTOX treatment in Treatment Cycle 1 to the qualification for retreatment | The time from the day of BOTOX treatment to the qualification for retreatment was estimated using a Kaplan-Meier survival method for each treatment group. Participants who did not qualify for retreatment were treated as censored at the time of their last study visit or study exit. |
| Change From Study Baseline in PinQ Item 'I am Worried That People Might Think my Clothes Smell Like Pee | From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1 | The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | From the first dose of study drug until the last dose, up to 147 weeks | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Italy, Netherlands, Norway, Poland, South Africa, United Kingdom, United States
Participant flow
Pre-assignment details
Participants were randomized in a 1:1:1 ratio to 1 of 3 treatment arms. Randomization was stratified by baseline daytime urinary urgency incontinence episodes (a total of ≤ 6 episodes or \> 6 episodes over the 2-day bladder diary collection period).
Participants by arm
| Arm | Count |
|---|---|
| BOTOX 25 U (BOTOX-Treated Population) Participants received 25 U BOTOX in Treatment Cycle 1 | 18 |
| BOTOX 50 U (BOTOX-Treated Population) Participants received 50 U BOTOX in Treatment Cycle 1 | 17 |
| BOTOX 100 U (BOTOX-Treated Population) Participants received 100 U BOTOX in Treatment Cycle 1 | 20 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 1 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 |
| Overall Study | Other, not specified | 4 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | BOTOX 25 U (BOTOX-Treated Population) | BOTOX 50 U (BOTOX-Treated Population) | BOTOX 100 U (BOTOX-Treated Population) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 18 Participants | 17 Participants | 20 Participants | 55 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 13.7 years STANDARD_DEVIATION 1.49 | 14.3 years STANDARD_DEVIATION 1.86 | 14.0 years STANDARD_DEVIATION 1.75 | 14.0 years STANDARD_DEVIATION 1.69 |
| Daily Frequency of Daytime Urinary Incontinence Episodes | 5.29 number of episodes STANDARD_DEVIATION 3.447 | 3.54 number of episodes STANDARD_DEVIATION 2.696 | 3.64 number of episodes STANDARD_DEVIATION 2.951 | 4.15 number of episodes STANDARD_DEVIATION 3.1 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not reported | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 12 Participants | 17 Participants | 41 Participants |
| Sex: Female, Male Female | 16 Participants | 17 Participants | 14 Participants | 47 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 29 | 0 / 33 | 0 / 18 | 0 / 17 | 0 / 20 | 0 / 55 | 0 / 1 | 0 / 17 | 0 / 28 | 0 / 46 | 0 / 2 | 0 / 7 | 0 / 13 | 0 / 22 | 0 / 0 | 0 / 1 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 12 / 18 | 23 / 29 | 24 / 33 | 12 / 18 | 12 / 17 | 14 / 20 | 38 / 55 | 1 / 1 | 13 / 17 | 18 / 28 | 32 / 46 | 1 / 2 | 3 / 7 | 8 / 13 | 12 / 22 | 0 / 0 | 1 / 1 | 1 / 3 | 2 / 4 |
| serious Total, serious adverse events | 1 / 18 | 0 / 29 | 1 / 33 | 1 / 18 | 0 / 17 | 0 / 20 | 1 / 55 | 0 / 1 | 0 / 17 | 1 / 28 | 1 / 46 | 0 / 2 | 0 / 7 | 1 / 13 | 1 / 22 | 0 / 0 | 0 / 1 | 0 / 3 | 0 / 4 |
Outcome results
Primary
Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1
Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
Time frame: From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1 | -1.37 urinary incontinence episodes per day | Standard Error 0.801 |
| BOTOX 50 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1 | -0.97 urinary incontinence episodes per day | Standard Error 0.811 |
| BOTOX 100 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1 | -2.35 urinary incontinence episodes per day | Standard Error 0.746 |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group as factor. A hierarchical analysis strategy to adjust for multiplicity was used.p-value: =0.380295% CI: [-3.203, 1.243]ANCOVA
Comparison: Treatment Difference of 50 U versus 25 U~Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group as factor. A hierarchical analysis strategy to adjust for multiplicity was used.p-value: =0.73395% CI: [-1.921, 2.712]ANCOVA
Secondary
Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ)
The PinQ is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time) and a total sum score is calculated (from 0 to 80), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement.
Time frame: From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ) | -6.96 units on a scale | Standard Error 2.841 |
| BOTOX 50 U (BOTOX-Treated Population) | Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ) | -5.11 units on a scale | Standard Error 3.243 |
| BOTOX 100 U (BOTOX-Treated Population) | Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ) | -8.28 units on a scale | Standard Error 2.979 |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.748195% CI: [-9.553, 6.909]ANCOVA
Comparison: Treatment Difference of 50 U versus 25 U~Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.669195% CI: [-6.799, 10.498]ANCOVA
Secondary
Change From Study Baseline in PinQ Item 'I am Worried That People Might Think my Clothes Smell Like Pee
The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement.
Time frame: From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'I am Worried That People Might Think my Clothes Smell Like Pee | -0.06 units on a scale | Standard Error 0.238 |
| BOTOX 50 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'I am Worried That People Might Think my Clothes Smell Like Pee | -0.37 units on a scale | Standard Error 0.273 |
| BOTOX 100 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'I am Worried That People Might Think my Clothes Smell Like Pee | -0.09 units on a scale | Standard Error 0.251 |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.929795% CI: [-0.721, 0.661]ANCOVA
Comparison: Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.397695% CI: [-1.022, 0.413]ANCOVA
Secondary
Change From Study Baseline in PinQ Item 'I Miss Out on Being With Friends Because of my Bladder Problems
The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement.
Time frame: From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'I Miss Out on Being With Friends Because of my Bladder Problems | -0.39 units on a scale | Standard Error 0.193 |
| BOTOX 50 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'I Miss Out on Being With Friends Because of my Bladder Problems | -0.24 units on a scale | Standard Error 0.218 |
| BOTOX 100 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'I Miss Out on Being With Friends Because of my Bladder Problems | -0.27 units on a scale | Standard Error 0.201 |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.668995% CI: [-0.434, 0.67]ANCOVA
Comparison: Treatment Difference of 50 U versus 25 U~Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.607695% CI: [-0.431, 0.729]ANCOVA
Secondary
Change From Study Baseline in PinQ Item 'My Bladder Problem Makes me Feel Bad About Myself
The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement.
Time frame: From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'My Bladder Problem Makes me Feel Bad About Myself | -0.54 units on a scale | Standard Error 0.209 |
| BOTOX 50 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'My Bladder Problem Makes me Feel Bad About Myself | -0.15 units on a scale | Standard Error 0.238 |
| BOTOX 100 U (BOTOX-Treated Population) | Change From Study Baseline in PinQ Item 'My Bladder Problem Makes me Feel Bad About Myself | -0.24 units on a scale | Standard Error 0.22 |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.330995% CI: [-0.311, 0.904]ANCOVA
Comparison: Treatment Difference of 50 U versus 25 U~Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.223595% CI: [-0.245, 1.024]ANCOVA
Secondary
Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition Episodes
Micturition was defined as toilet voids recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime micturition episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
Time frame: From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition Episodes | -1.84 micturition episodes per day | Standard Error 1.027 |
| BOTOX 50 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition Episodes | 0.31 micturition episodes per day | Standard Error 1.014 |
| BOTOX 100 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition Episodes | -1.02 micturition episodes per day | Standard Error 0.983 |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.574395% CI: [-2.082, 3.713]ANCOVA
Comparison: Treatment Difference of 50 U versus 25 U~Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.145195% CI: [-0.769, 5.078]ANCOVA
Secondary
Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency Episodes
Participants recorded daytime urgency episodes in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime urgency episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
Time frame: From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency Episodes | -1.85 urgency episodes per day | Standard Error 1.014 |
| BOTOX 50 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency Episodes | -1.78 urgency episodes per day | Standard Error 0.998 |
| BOTOX 100 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency Episodes | -2.18 urgency episodes per day | Standard Error 0.945 |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.820695% CI: [-3.205, 2.551]ANCOVA
Comparison: Treatment Difference of 50 U versus 25 U~Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.960495% CI: [-2.807, 2.95]ANCOVA
Secondary
Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL)
The volume per micturition was derived from the total urine volume voided over 1 daytime period during the 2-day bladder diary collection period divided by the number of voids in the same daytime period. Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
Time frame: From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL) | -9.17 mL | Standard Error 15.924 |
| BOTOX 50 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL) | 24.94 mL | Standard Error 17.047 |
| BOTOX 100 U (BOTOX-Treated Population) | Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL) | 26.16 mL | Standard Error 15.9 |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.117495% CI: [-9.207, 79.873]ANCOVA
Comparison: Treatment Difference of 50 U versus 25 U~Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using an ANCOVA model with study baseline value as covariate, and treatment group and stratification (baseline daytime urinary urgency incontinence episodes \[a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period\]) as factors. A hierarchical analysis strategy to adjust for multiplicity was not implemented.p-value: =0.156795% CI: [-13.536, 81.76]ANCOVA
Secondary
Percentage of Participants With a Positive Treatment Response in the Modified Treatment Benefit Scale
The Modified Treatment Benefit Scale (Modified TBS) is a single-item scale designed to assess the change in the participant's overactive bladder (OAB) condition following treatment. The participant's current condition (urinary problems, urinary incontinence) is compared to their condition prior to receipt of any study treatment by selection of greatly improved, improved, not changed or worsened. Participants who selected greatly improved or improved were considered to have a positive treatment response.
Time frame: At Week 12 in Treatment Cycle 1
Population: Participants with non-missing values at Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Percentage of Participants With a Positive Treatment Response in the Modified Treatment Benefit Scale | 52.9 percentage of participants |
| BOTOX 50 U (BOTOX-Treated Population) | Percentage of Participants With a Positive Treatment Response in the Modified Treatment Benefit Scale | 70.6 percentage of participants |
| BOTOX 100 U (BOTOX-Treated Population) | Percentage of Participants With a Positive Treatment Response in the Modified Treatment Benefit Scale | 68.4 percentage of participants |
Comparison: Treatment Difference of 100 U versus 25 U~Pairwise comparisons of 100 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using the Cochran-Mantel-Haenszel (CMH) method stratified by baseline daytime urinary urgency incontinence episodes (a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period).p-value: =0.609295% CI: [-18.94, 46.19]Cochran-Mantel-Haenszel
Comparison: Treatment Difference of 50 U versus 25 U~Pairwise comparisons of 50 U versus 25 U of BOTOX up to Week 12 in Treatment Cycle 1 was evaluated using the Cochran-Mantel-Haenszel (CMH) method stratified by baseline daytime urinary urgency incontinence episodes (a total of ≤ 6 episodes or \> 6 episodes over the 2-day diary collection period).p-value: =0.482495% CI: [-16.2, 48.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Night Time Urinary Incontinence
Urinary incontinence was defined as involuntary loss of urine. Participants recorded night time urinary incontinence episodes in a bladder diary during 2 consecutive days in the week prior to the study visit. Night time is defined as the time between going to bed to sleep for the night and waking up to start the next day. The number of daily night time urinary incontinence episodes were averaged during the 2-day period. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle.
Time frame: From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1
Population: Participants with analysis values at both baseline and Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-0 nights | 22.2 percentage of participants |
| BOTOX 25 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-0 nights | 50.0 percentage of participants |
| BOTOX 25 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-2 nights | 50.0 percentage of participants |
| BOTOX 25 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-1 night | 27.8 percentage of participants |
| BOTOX 25 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-1 night | 22.2 percentage of participants |
| BOTOX 25 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-2 nights | 27.8 percentage of participants |
| BOTOX 50 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-2 nights | 35.3 percentage of participants |
| BOTOX 50 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-1 night | 5.9 percentage of participants |
| BOTOX 50 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-0 nights | 52.9 percentage of participants |
| BOTOX 50 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-1 night | 11.8 percentage of participants |
| BOTOX 50 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-0 nights | 76.5 percentage of participants |
| BOTOX 50 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-2 nights | 17.6 percentage of participants |
| BOTOX 100 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-2 nights | 35.0 percentage of participants |
| BOTOX 100 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-0 nights | 50.0 percentage of participants |
| BOTOX 100 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Week 12-1 night | 15.0 percentage of participants |
| BOTOX 100 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-0 nights | 35.0 percentage of participants |
| BOTOX 100 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-2 nights | 50.0 percentage of participants |
| BOTOX 100 U (BOTOX-Treated Population) | Percentage of Participants With Night Time Urinary Incontinence | Baseline-1 night | 15.0 percentage of participants |
Secondary
Time to Participant's First Request for Retreatment
The time from the day of BOTOX treatment to the request for the subsequent treatment was estimated using a Kaplan-Meier survival method for each treatment group. Participants who did not request retreatment were treated as censored at the time of their last study visit or study exit.
Time frame: From the day of BOTOX treatment in Treatment Cycle 1 to the request for subsequent treatment
Population: BOTOX-treated participants who requested retreatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Time to Participant's First Request for Retreatment | 16.6 weeks |
| BOTOX 50 U (BOTOX-Treated Population) | Time to Participant's First Request for Retreatment | 17.6 weeks |
| BOTOX 100 U (BOTOX-Treated Population) | Time to Participant's First Request for Retreatment | 21.3 weeks |
Secondary
Time to Participant's Qualification for Retreatment
The time from the day of BOTOX treatment to the qualification for retreatment was estimated using a Kaplan-Meier survival method for each treatment group. Participants who did not qualify for retreatment were treated as censored at the time of their last study visit or study exit.
Time frame: From the day of BOTOX treatment in Treatment Cycle 1 to the qualification for retreatment
Population: BOTOX-treated participants who qualified for retreatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Time to Participant's Qualification for Retreatment | 22.5 weeks |
| BOTOX 50 U (BOTOX-Treated Population) | Time to Participant's Qualification for Retreatment | 18.1 weeks |
| BOTOX 100 U (BOTOX-Treated Population) | Time to Participant's Qualification for Retreatment | 24.1 weeks |
Other Pre-specified
Number of Participants With Treatment Emergent Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Time frame: From the first dose of study drug until the last dose, up to 147 weeks
Population: All participants enrolled into the study who received at least 1 BOTOX treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BOTOX 25 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 1 | 13 Participants |
| BOTOX 25 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 3 | 1 Participants |
| BOTOX 25 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 2 | 1 Participants |
| BOTOX 50 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 3 | 3 Participants |
| BOTOX 50 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 1 | 12 Participants |
| BOTOX 50 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 2 | 13 Participants |
| BOTOX 50 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 4 | 1 Participants |
| BOTOX 100 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 4 | 1 Participants |
| BOTOX 100 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 2 | 18 Participants |
| BOTOX 100 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 3 | 8 Participants |
| BOTOX 100 U (BOTOX-Treated Population) | Number of Participants With Treatment Emergent Adverse Events | Cycle 1 | 14 Participants |