A Study to Test the Effects of Tolterodine Tartrate in Patients With Overactive Bladder (0000-107)

A Randomized, Placebo Controlled, Crossover Study to Evaluate the Effects of Tolterodine Tartrate on Urodynamic Parameters in Patients With Overactive Bladder

This study will design an alternative urodynamic platform to better evaluate treatment effects of medications for overactive bladder. Part II is dependent on results of Part I and may not be conducted.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: tolterodine tartrate; Drug: Comparator: Placebo to tolterodine tartrate

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient is a postmenopausal female 40 to 75 years of age
• Patient has a Body Mass Index (BMI) less than or equal to 35 kg/m2
• Patient has a documented history of overactive bladder for at least 6 months prior to screening

Exclusion Criteria:

• Patient has stress or mixed incontinence
• Patient has a history of interstitial cystitis, painful bladder syndrome, or chronic pelvic pain
• Patient has a history of stroke, seizures, or major neurological disorders
• Patient has a history of fecal incontinence
• Patient has a history of continual urine leakage
• Patient has had surgery to correct stress urinary incontinence or pelvic organ prolapse within 6 months of study start
• Patient received bladder training of electrostimulation within 2 weeks of study start
• Patient requires a catheter
• Patient is taking medications that cannot be stopped for the duration of the trial including certain anticholinergics or smooth muscle relaxants
• Patient began taking tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, calcium channel blockers, ephedrine/pseudoephedrine, or diuretic therapy less than 8 weeks before study start
• Patient has been on hormone replacement therapy for less than 12 weeks at study start
• Patient must take medication for arrhythmia
• Patient consumes more than 2 alcoholic beverages per day
• Patient consumes more than 3 servings of caffeinated beverages per day (1 serving = 120 mg caffeine)
• Patient has multiple and/or severe allergies to foods and drugs
• Patient regularly uses any illegal drugs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Part I, Sequence 1: tolterodine tartrate crossing over to matching placebo	Drug: tolterodine tartrate; Part I: tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose tolterodine tartrate 4 mg capsule; Drug: Comparator: Placebo to tolterodine tartrate; Part I: placebo to tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: placebo to tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose placebo to tolterodine tartrate 4 mg capsule
Experimental: 2; Part I, Sequence 2: placebo crossing over to study drug 4 mg once a Day (qd)	Drug: tolterodine tartrate; Part I: tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose tolterodine tartrate 4 mg capsule; Drug: Comparator: Placebo to tolterodine tartrate; Part I: placebo to tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: placebo to tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose placebo to tolterodine tartrate 4 mg capsule
Experimental: 3; Part II, Sequence 1: study drug crossing over to placebo	Drug: tolterodine tartrate; Part I: tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose tolterodine tartrate 4 mg capsule; Drug: Comparator: Placebo to tolterodine tartrate; Part I: placebo to tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: placebo to tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose placebo to tolterodine tartrate 4 mg capsule
Experimental: 4; Part II, Sequence 2: placebo crossing over to study drug	Drug: tolterodine tartrate; Part I: tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose tolterodine tartrate 4 mg capsule; Drug: Comparator: Placebo to tolterodine tartrate; Part I: placebo to tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: placebo to tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose placebo to tolterodine tartrate 4 mg capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 7 on Tolterodine 4 mg and Placebo	Change from baseline in maximum cystometric capacity at 4 hours post dose 7 on tolterodine 4 mg and placebo (analysis on natural log transformed data)	4 hours post dose 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 1 on Tolterodine 4 mg and Placebo	Change from baseline in maximum cystometric capacity at 4 hours post dose 1 on tolterodine 4 mg and placebo (analysis on natural log transformed data)	4 hours post dose 1

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Frenkl T, Railkar R, Shore N, Bailen J, Sutherland S, Burke J, Scott BB, Ruddy M, Beals C. Evaluation of an experimental urodynamic platform to identify treatment effects: a randomized, placebo-controlled, crossover study in patients with overactive bladder. Neurourol Urodyn. 2012 Jan;31(1):69-74. doi: 10.1002/nau.21094. Epub 2011 Sep 8.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2008
• Primary Completion (Actual): January 19, 2009
• Study Completion (Actual): January 19, 2009

Study Registration Dates

• First Submitted: October 7, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (Estimate): October 8, 2008

Study Record Updates

• Last Update Posted (Actual): February 22, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Tolterodine Tartrate
• Other Study ID Numbers: 0000-107; 2008_560