Efficacy of Sanctura XR (Trospium Chloride) for Reducing Overactive Bladder Symptoms in Female Subjects Refractory to Detrol LA (Tolterodine Tartrate Extended Release) Daily

Study Overview
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Brief Summary
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This study will investigate the safety and efficacy of Sanctura XR (trospium chloride) daily in reducing urgency, urinary frequency and urinary urge incontinence in female patients with incontinence refractory to Detrol LA (tolterodine tartrate extended release) 4 mg therapy.

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: trospium chloride
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Taking Detrol® LA 4mg daily for a minimum of 1 month prior to Screening/Qualification Overactive Bladder syndrome with urgency, urinary frequency and urgency urinary incontinence Taking five or more concomitant medications (may be prescription, non-prescription, or supplement/vitamin) daily for indications other than Overactive Bladder (OAB). Exclusion Criteria: Predominant stress or insensate incontinence History of neurogenic bladder Two urinary tract infections in the last six months Gastric by-pass (Roux-en-Y) surgery (adjustable gastric banding is allowed) Donated >500mL blood in the 30 days prior to the screening visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Experimental: Sanctura XR®<br>Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks. | Drug: trospium chloride<br>* Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks<br>* Other names: Sanctura XR®;|
| Placebo Comparator: Placebo<br>Placebo once daily on an empty stomach for 14 weeks. | Drug: placebo<br>* Placebo once daily on an empty stomach for 14 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Continent (PPC) | PPC is the percentage of patients with complete continence (without any urgency urinary incontinence episodes) during the 3-day bladder diary period associated with the Week 14 visit. | Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Continent Days Per Week (CDW) | Continent Days per Week is the average of the number of times an individual has no incontinence episodes in a day within the 3-day collection period calculated as 7 x (number of dry days within the 3-day diary period) divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A positive change from Baseline (more continent/fewer incontinent days per week ) indicated improvement. | Baseline, Week 14 | 
| Change From Baseline in Nocturic Toilet Voids | A nocturic (nighttime) toilet void is identified if the patient marks Yes for both Toilet Voiding and Sleep Interruption in the 3-day bladder diary. The daily average number of nocturic toilet voids is obtained as the sum of all nighttime toilet voids over the 3-day bladder diary period divided by number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline (fewer nocturic toilet voids) indicated improvement. | Baseline, Week 14 | 
| Change From Baseline in Urgency-Related Toilet Voids | Urgency-related toilet void (or urinary urgency) is identified if the patient marks Yes for both Urgency Association Void and Toilet Voiding in the 3-day bladder diary. The daily average number of urgency-related voids is calculated as the sum of all urgency episodes over the 3-day bladder diary period divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline (fewer urgency related toilet voids) indicated improvement. | Baseline, Week 14 | 
| Change From Baseline in Daily Average Overactive Bladder-Symptom Composite Score (OAB-SCS) | The OAB-SCS is derived from the 3-day bladder diary which includes: 1) 24-hour voiding frequency; 2) the Indevus Urgency Severity Scale (IUSS) Score (0=no urgency, 1=aware of urgency but is tolerable, 2=urgency discomfort interferes with activities/tasks, 3=extreme urgency discomfort that abruptly stops activities/tasks associated with each toilet void); and 3) the frequency of Urgency Urinary Incontinence episodes. Each toilet void is then assigned a point value from 1 (IUSS Score=0) to 5 (UUI episode not associated with a toilet void). The daily average OAB-SCS is then calculated based on the diary entries and assigned point values. The lowest possible daily average OAB-SCS is 0 (corresponding to no urgency in every void). There is no upper limit since the score is based on the number of voids per day. Scores <= 30 indicate mild OAB, scores > 30 to 39 indicate moderate OAB, and scores >= 40 indicate severe OAB. A negative change from Baseline indicated improvement. | Baseline, Week 14 | 
| Change From Baseline in Voided Volume | Average volume of urine voided per toilet void is calculated by total volume collected in a 24-hour diary period divided by the number of individual entries of volume voided in that period. A positive change from Baseline (greater volume voided) indicated improvement. A negative change from Baseline (less volume voided) indicated a worsening. | Baseline, Week 14 | 
| Change From Baseline in Urgency Severity | The urgency severity per toilet void is based on the Indevus Urgency Severity Scale (IUSS). The patient recorded urinary urgency severity in a 3-day bladder diary using a 4-point scale: 0=None-no urgency (best), 1=Slight-aware of urgency but is tolerable, 2=Moderate-urgency discomfort interferes with activities/tasks, 3=Severe-extreme urgency discomfort that abruptly stops activities/tasks (worst). Urgency Severity is calculated as the sum of all IUSS scores during the 3-day diary period divided by the number of toilet voids recorded during that period. A negative change from Baseline indicated improvement. | Baseline, Week 14 | 
| Change From Baseline in Urgency Urinary Incontinence (UUI) | Urgency urinary incontinence is identified if the patient marks Yes for both Accidental Leakage and Urgency Associated Void in the 3-day bladder diary, and the Urgency Severity score is ≥ 1. Average daily episodes of UUI is calculated as the sum of all UUI episodes over 3-day diary period divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline indicated improvement. | Baseline, Week 14 |