Premarin Versus Toviaz for Treatment of Overactive Bladder

Study Overview
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Brief Summary
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The use of vaginal estrogen cream in conjunction with Toviaz will be more effective than the use of Toviaz alone for the treatment of overactive bladder.

Detailed Description
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Participants will be randomized to two treatment arms with 45 patients enrolled in each study arm: Toviaz and Premarin Vaginal Cream and Toviaz and Placebo Premarin Vaginal Cream. The Toviaz will be dosed at 4mg tablet given as a once daily dose. Premarin vaginal cream will be dosed at 1 gram per vagina twice weekly. Compliance will be assessed at the 4-week mark and again at completion of the study, 8 weeks after the commencement of treatment. The questionnaires chosen for this study have been designed and validated as effective tools to assess and evaluate OAB. Patients will be asked to complete three symptoms questionnaires and a 3-day voiding dairy. The questionnaires include Overactive Bladder Questionnaire (OAB-q), The Patient Perception of Bladder Condition, and Urgency Severity and Impact Questionnaire. The voiding diary and questionnaires will be filled out and collected at the initial visit and again at the end of the study which is defined as 8 weeks after the commencement of treatment. Additionally, patients will be asked to rate their symptoms associated with urogenital atrophy at the start of the study and then again at 8 weeks. The severity of each symptom will be graded based on a four-point scale (0=none, 1=mild, 2= moderate, 3=severe) and a composite score will then be generated. Examiners will also rate the severity of signs of urogenital atrophy at the first visit and at the conclusion of the study. An objective evaluation of the effectiveness of the estrogen cream treatment will be accomplished by a pathological evaluation of the vaginal cell samples at the beginning of treatment and then again at the 8 week point. These cells will be collected and analyzed by an independent pathologist to determine the percentage of parabasal, intermediate, and superficial cells and to document the change in these three categories of cells as a result of the vaginal estrogen treatment. A 3-Day voiding diary will be used to document changes from baseline for urinary urgency, frequency, and incontinence episodes. Based on previous studies we predict there will be a 45% improvement on urinary frequency from baseline when using both Toviaz and vaginal Premarin cream. Secondary outcomes will be measured using the following validated questionnaires given at the start of the study and again at completion: OAB-q, Patient Perception of Bladder Condition, Urgency Severity and Impact Questionnaire.

Official Title
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A Combined Treatment Program for the Symptoms of Urinary Urgency and Frequency With Toviaz and Premarin Vaginal Cream

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: Toviaz
* Drug: Premarin
* Drug: Placebo cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal Women defined as at least 12 months since last menstrual period OAB symptoms for 6 months or longer with complaints of frequency (8 or more voids in a 24 hour period), and either 6 or more urgency episodes in 24 hours, and either 3 or more urge urinary incontinence episodes per 24 hours. Exclusion Criteria: Current or recent treatment (within the last 6 months) with estrogens Past or present history of estrogen dependent neoplasm Undiagnosed genital tract bleeding Current urinary or vaginal infection History of thromboembolic disorders associated with estrogen use Commencement or alteration of diuretic therapy within three months of study enrollment No contraindications for anticholinergic medical therapy No contraindications to estrogen therapy Symptoms must not have commenced more than three years prior to menopause Post Void Residual must be under or equal to 150 ml Recurrent Urinary Tract Infections (3 culture proven UTI's within the past 12 months) Not on any other anticholinergic medications for the last 4 weeks Painful Bladder Syndrome Chronic Pelvic Pain Vaginal Prolapse POPQ > stage 2/ maximal prolapse point greater than +1 cm

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Toviaz and Premarin Vaginal Cream<br>Toviaz 4 mg PO q day and premarin cream 1 g per vagina 2 times a week. | Drug: Toviaz<br>* Toviaz 4mg daily<br>* Other names: fesoteridine;Drug: Premarin<br>* Premarin cream 1 g per vagina twice weekly<br>* Other names: estrogen, conjugated vaginal;|
| Placebo Comparator: Toviaz , Placebo Premarin Vaginal Cream<br>Toviaz 4 mg PO q day and placebo cream 1 g per vagina 2 times a week. | Drug: Toviaz<br>* Toviaz 4mg daily<br>* Other names: fesoteridine;Drug: Placebo cream<br>* Placebo cream 1 g per vagina twice weekly, to mimic Premarin cream<br>* Other names: Verba base cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary frequency as measured by a 3 day voiding diary | number of voids per day | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lifestyle Impact of Overactive Bladder as measured using 3 validated questionnaires: OAB-Q, PPBC, and Urgency Severity and Impact Questionnaire | quality of life assessment via questionnaire | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overactive Bladder, Vaginal Estrogen, Anticholinergics, Antimuscarinics