Premarin Versus Toviaz for Treatment of Overactive Bladder

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

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.

Study Overview

• Status: Unknown
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: Toviaz; Drug: Premarin; Drug: Placebo cream

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Alexandriah Alas, MD; Phone Number: 954-659-6342; Email: alasa@ccf.org
• Study Contact Backup: Name: Eric Hurtado, MD; Phone Number: 954-659-5559; Email: hurtade@ccf.org

Study Locations

• United States
  • Florida
    • Weston, Florida, United States, 33331
      • Recruiting
      • Cleveland Clinic Florida
      • Contact: Alexandriah Alas, MD; Phone Number: 954-659-6342; Email: alasa@ccf.org
      • Sub-Investigator: GW Davila, MD
      • Sub-Investigator: Leon Plowright, MD
      • Sub-Investigator: Vivian Aguilar, MD
      • Sub-Investigator: Alexandriah Alas, MD
      • Sub-Investigator: Luis Espaillat, MD
      • Principal Investigator: Eric Hurtado, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Toviaz and Premarin Vaginal Cream; Toviaz 4 mg PO q day and premarin cream 1 g per vagina 2 times a week.	Drug: Toviaz; Toviaz 4mg daily; Other Names: fesoteridine; Drug: Premarin; Premarin cream 1 g per vagina twice weekly; Other Names: estrogen, conjugated vaginal
Placebo Comparator: Toviaz , Placebo Premarin Vaginal Cream; Toviaz 4 mg PO q day and placebo cream 1 g per vagina 2 times a week.	Drug: Toviaz; Toviaz 4mg daily; Other Names: fesoteridine; Drug: Placebo cream; Placebo cream 1 g per vagina twice weekly, to mimic Premarin cream; Other Names: Verba base cream

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: Pfizer
• Investigators: Principal Investigator: Eric Hurtado, MD, Cleveland Clinic Florida

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Anticipated): April 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: May 24, 2012
• First Submitted That Met QC Criteria: June 4, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Actual): April 20, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Overactive Bladder; Antimuscarinics; Vaginal Estrogen; Anticholinergics
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estrogens, Conjugated (USP)
• Other Study ID Numbers: 11074

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No