Official Title: “Exploring Predictors of Symptoms Relapse After Discontinuation of Successful 3-Month of Treatment With a Tolterodine Prolonged Release Capsules (4 mg, Once Daily) in Overactive Bladder Patients: A Prospective Trial”

This is a Phase IV, prospective and multi-center study to find risk factors of OAB symptoms relapse in patients who showed therapeutic benefits after 3 months of treatment with Tolterodine SR and who then discontinued these antimuscarinics for 3 month.

Patients eligible to this study will be treated with Tolterodine SR 4mg for 3 months. After completion of the treatment period, subjects will be evaluated for OAB symptoms. Only the patients who have the therapeutic effects will be discontinue the drug. After 1, 3 month after drug discontinuation, OAB symptoms will be re-evaluated.

Study Type: Interventional

Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Study Primary Completion Date: October 2009

Primary Objective: - To investigate the risk factors (clinical and urodynamic) of OAB symptom relapse in patients who showed therapeutic benefits after 3 months of treatment with Tolterodine SR and who then discontinued these antimuscarinics for 3 month.

Secondary Objective: - To investigate the change of the patient perception and quality of life after antimuscarinic discontinuation - To find the rate of patients who have OAB symptom relapse. - To find the risk factors of patients who want retreatment. - To find the rate of patients who want retreatment.

Intervention(s) in this Clinical Trial

• Drug: Tolterodine
  • Extended release tolterodine tartrate 4 mg, once daily, for 3 months

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Tolterodine

Primary Measures

• Risk factors and relapse rate of the OAB symptoms after drug discontinuation
  • Time Frame: from baseline (after 3 months treatment) to 1, 3 month after drug discontinuation
    Safety Issue?: No

Secondary Measures

• Micturition diary efficacy parameters
  • Time Frame: from baseline (after 3 months treatment) to 1, 3 month after drug discontinuation
    Safety Issue?: No
• Quality of life parameters: change in total score and subscale scores of OAB-questionnaire
  • Time Frame: from baseline (after 3 months treatment) to 1, 3 month after drug discontinuation
    Safety Issue?: No
• Patient perceptions: change in patient perception of urgency, change in patient perception of bladder condition and percentage of patients who wants retreatment
  • Time Frame: from baseline (after 3 months treatment) to 1, 3 month after drug discontinuation
    Safety Issue?: No

Inclusion Criteria:

• 1. Male or female aged 18≤and ≤80 years
• 2. Symptoms of urinary urgency (defined as a level of 3 to 5 in a 5 point Urinary
• Sensation Scale) over 2 times per day
• 3. Symptoms of urinary frequency (≥ 10 micturitions per 24 hours) as verified by baseline micturition diary.
• 4. Symptoms of overactive bladder, including urinary urge incontinence, urgency and/or frequency for ≥6 months.
• 5. Ability and willingness to correctly complete the micturition diary and questionnaire
• 6. Capable of understanding and having signed the informed consent form after full discussion of the research nature of the treatment and its risks and benefits

Exclusion Criteria:

• 1. Clinical significant stress incontinence as determined by the investigator and confirmed for female patients by a cough provocation test
• 2. An average volume voided of > 200 ml per micturition as verified on the baseline micturition diary
• 3. Total daily urine volume of > 3000 ml as verified on the baseline micturition diary
• 4. Significant hepatic or renal disease, defined as having twice the upper limit of the reference ranges for serum concentrations of aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT]), alkaline phosphatase or creatinine
• 5. Any condition that is a contraindication for anticholinergic treatment, including uncontrolled narrow-angled glaucoma, urinary retention or gastric retention
• 6. Symptomatic acute urinary tract infection (UTI) during the run-in period
• 7. Recurrent UTIs defined as having been treated for symptomatic UTIs > 4 times in the last year
• 8. Diagnosed or suspected interstitial cystitis
• 9. Uninvestigated hematuria or hematuria secondary to malignant disease.
• 10. Clinically significant bladder outlet obstruction defined by clinical symptoms and investigator's opinion according to local standard of care
• 11. Patients with marked cystocele or other clinically significant pelvic prolapse.
• 12. On an unstable dosage of any drug with anticholinergic side effects, or expected to start such treatment during the study
• 13. Receipt of any electrostimulation or bladder training within the 14 days before the start of tolterodine SR, or expected to start such treatment during the study
• 14. Use of any other drugs for the treatment of overactive bladder (e.g. anticholinergics except tolterodine) within the 14 days before the start of tolterodine SR, or expected to start such treatment during the study
• 15. An indwelling catheter or practicing intermittent self-catheterization
• 16. Use of any investigational drug within 2 months preceding the start of the study
• 17. Patients with chronic constipation or history of severe constipation
• 18. Pregnant or nursing women
• 19. Sexually active females of childbearing potential not using reliable contraception for at least 1 month prior to study start and not agreeing to use such methods during the entire study period and for at least 1 month thereafter. Reliable contraceptive methods are defined as intrauterine devices (IUDs), combination type contraceptive pills, hormonal implants, double barrier method, injectable contraceptives and surgical procedures (tubal ligation or vasectomy).
• 20. Patients who have bladder cancer or prostate cancer
• 21. Treatment with potent CYP3A4 inhibitors, such as cyclosporine, vinblastine, macrolide antibiotics (e.g. erythromycin, clarithromycin, azithromycin) or antifungal agents (e.g. ketoconazole, itraconazole, micronazole).
• 22. Any other condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Samsung Medical Center

Overall Clinical Trial Officials and Contacts

Kyu-Sung Lee, Ph.D Principal Investigator Samsung Medical Center  

Overall Contact: Kyu-Sung Lee, Ph.D 82-2-3410-3554 ksleedr@skku.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00730535

Study ID Number: 2005-08-069

ClinicalTrials.gov Identifier: NCT00730535

Health Authority: South Korea: Korea Food and Drug Administration (KFDA)