A Study Evaluating the Efficacy and Safety of BOTOX® or Solifenacin in Patients With Overactive Bladder and Urinary Incontinence

Study Overview
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Brief Summary
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A study to evaluate the efficacy and safety of BOTOX® or Solifenacin in patients with overactive bladder (OAB) and urinary incontinence.

Conditions
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Overactive Bladder, Urinary Incontinence

Intervention / Treatment
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* Biological: BOTOX®
* Drug: solifenacin
* Drug: Botox placebo (normal saline)
* Drug: solifenacin placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of Overactive Bladder (OAB) (frequency/urgency) with urinary incontinence for at least 6 months Inadequate response or limiting side effects with anticholinergics for the treatment of OAB Exclusion Criteria: Overactive Bladder caused by neurological condition Patient has predominance of stress incontinence Use of anticholinergics or other medications to treat OAB symptoms in the 7 days prior to screening Previous use of solifenacin History or evidence of pelvic or urological abnormality Previous use of any botulinum toxin of any serotype for any urological condition Previous use of any botulinum toxin of any serotype for any non-urological condition within 12 weeks of randomization Diagnosis of Myasthenia gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BOTOX®<br>Treatment Cycle 1: BOTOX injected at Day 1 with one solifenacin placebo capsule taken orally once daily for up to 24 weeks. After a minimum of 12 weeks, patients could request/qualify for a second BOTOX injection. | Biological: BOTOX®<br>* BOTOX 100U injected at Day 1 (BOTOX/solifenacin placebo arm). After a minimum of 12 weeks, all patients could request/qualify for a BOTOX injection.<br>* Other names: botulinum toxin Type A;Drug: solifenacin placebo<br>* Beginning on Day 1, one capsule taken orally once daily for up to 24 weeks.<br>|
| Active Comparator: solifenacin<br>Treatment Cycle 1: Oral solifenacin taken once daily starting at Day 1 for up to 24 weeks with intradetrusor injection of BOTOX placebo on Day 1. After a minimum of 12 weeks, patients could request/qualify for a BOTOX injection. | Biological: BOTOX®<br>* BOTOX 100U injected at Day 1 (BOTOX/solifenacin placebo arm). After a minimum of 12 weeks, all patients could request/qualify for a BOTOX injection.<br>* Other names: botulinum toxin Type A;Drug: solifenacin<br>* Beginning on Day 1, one 5 mg solifenicin capsule, with optional dose increase to 10 mg at Week 6, (both overencapsulated for blinding purposes) taken orally once daily for up to 24 weeks.<br>* Other names: Vesicare;Drug: Botox placebo (normal saline)<br>* Botox placebo (normal saline) intradetrusor injection at Day 1.<br>|
| Placebo Comparator: placebo<br>Treatment Cycle 1: One solifenacin placebo capsule taken orally once daily starting at Day 1 for up to 24 weeks with an intradetrusor injection of BOTOX placebo at Day 1. After a minimum of 12 weeks, patients could request/qualify for a BOTOX injection. | Biological: BOTOX®<br>* BOTOX 100U injected at Day 1 (BOTOX/solifenacin placebo arm). After a minimum of 12 weeks, all patients could request/qualify for a BOTOX injection.<br>* Other names: botulinum toxin Type A;Drug: Botox placebo (normal saline)<br>* Botox placebo (normal saline) intradetrusor injection at Day 1.<br>Drug: solifenacin placebo<br>* Beginning on Day 1, one capsule taken orally once daily for up to 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Study Baseline in Number of Episodes of Urinary Incontinence in Treatment Cycle 1 | Urinary incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary in the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of incontinence episodes are averaged daily during this period. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. | Study Baseline, Week 12 | 
| Percentage of Patients With 100% Reduction in Incontinence Episodes in Treatment Cycle 1 | Urinary incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary in the 3 consecutive days prior to the study visit in Treatment Cycle 1. The number of incontinence episodes are averaged daily during this period and compared to baseline to determine 100% reduction in episodes. | Study Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With a Positive Response on the Single-Item Treatment Benefit Scale During Treatment Cycle 1 | A positive treatment response on the Treatment Benefit Scale is a score of either 1 or 2, representing 'greatly improved' or 'improved.' | Week 12 | 
| Change From Study Baseline in the Number of Micturition Episodes in Treatment Cycle 1 | The number of micturition episodes (the number of times a patient urinates into the toilet) in Treatment Cycle 1 was recorded by the patient in a bladder diary during 3 consecutive days in the week prior to the visit. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. | Study Baseline, Week 12 | 
| Change From Study Baseline in the Number of Nocturia Episodes in Treatment Cycle 1 | Nocturia episodes are measured over a 3 day diary prior to each visit in Treatment Cycle 1. 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. | Study Baseline, Week 12 | 
| Change From Study Baseline in the Role Limitations Domain on the King's Health Questionnaire in Treatment Cycle 1 | The King's Health Questionnaire is a disease-specific questionnaire that measures the quality of life of patients with urinary incontinence. The questionnaire consists of 7 domains, including the role limitations domain. Domain scores range from 0 to 100, with a lower score indicating a preferable health status. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. | Study Baseline, Week 12 | 
| Change From Study Baseline in the Social Limitations Domain on the King's Health Questionnaire in Treatment Cycle 1 | The King's Health Questionnaire is a disease-specific questionnaire that measures the quality of life of patients with urinary incontinence. The questionnaire consists of 7 domains, including the social limitations domain. Domain scores range from 0 to 100, with a lower score indicating a preferable health status. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. | Study Baseline, Week 12 |