Evaluation of an Alternative Injection Paradigm for OnabotulinumtoxinA (BOTOX®) in the Treatment of Overactive Bladder in Patients With Urinary Incontinence

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate an Alternative Injection Paradigm for OnabotulinumtoxinA (BOTOX®) in the Treatment of Overactive Bladder in Patients With Urinary Incontinence (LO-BOT)

Conditions
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Urinary Bladder, Overactive, Urinary Incontinence

Intervention / Treatment
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* Biological: onabotulinumtoxinA
* Drug: Placebo (saline)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BOTOX® 100 U/BOTOX® 100 U<br>BOTOX® (onabotulinumtoxinA) 100 U injection into the bladder on Day 1 and a second injection BOTOX® 100 U after Week 12 if applicable. | Biological: onabotulinumtoxinA<br>* OnabotulinumtoxinA (BOTOX®) injection into the bladder.<br>* Other names: botulinum toxin Type A;|
| Placebo Comparator: Placebo/BOTOX® 100 U<br>Placebo (saline) injection into the bladder on Day 1 and a second injection BOTOX® 100 U after Week 12 if applicable. | Biological: onabotulinumtoxinA<br>* OnabotulinumtoxinA (BOTOX®) injection into the bladder.<br>* Other names: botulinum toxin Type A;Drug: Placebo (saline)<br>* Placebo (saline) injection into the bladder.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Complete Continence | Complete continence is defined as 100% reduction in urinary incontinence from Baseline. | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12] | 
| 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. | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12 | 
| 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. | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to 3 consecutive days prior to Week 12 | 
| 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. | Baseline (3 consecutive days during the Screening Period; within 35 days prior to Day 1) to, 3 consecutive days prior to Week 12 | 
| 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. | Week 12 |