Combination Treatment With Doxazosin Plus TolterodineSR 2 mg Versus 4mg in Men With an Overactive Bladder (OAB) and Benign Prostatic Hyperplasia (BPH)

Comparison of the Efficacy and Safety of Combination Treatment With Doxazosin Plus TolterodineSR 2 mg vs Doxazosin Plus TolterodineSR 4 mg in Men With an OAB/BPO: Randomized Controlled Study"

OAB occurs in approximately 50% to 75% of men with BPO and up to 38% of men with BPO continue to suffer from OAB after relief the obstruction.Symptoms of OAB are more bothersome than the voiding complaints of slow stream and hesitancy. However, the patients with both BPO and OAB are often not treated with muscarinic receptor antagonists due to concern that they will experience acute urinary retention.

Tolterodine is a potent and pure muscarinic receptor antagonist that was developed specifically for the treatment of overactive bladder. Recently, studies revealed that tolterodine was effective, safe and well tolerated in adults with OAB and urodynamically confirmed BPO.However, the optimal dosage of antimuscarinic for the treatment of OAB coexisting BPO was not yet fully assessed. In real clinical situation, some patients complain voiding difficulty after addition of antimuscarinics and want to stop antimuscarinics.It is probable that a lower dosage of antimuscarinics combined with alpha-adrenergic antagonists can be used safely in OAB patients with BOO, with the same efficacy.

This study is designed to investigate the optimal doses of tolterodine SR in combination with doxazosin in men with both BOO and OAB based on efficacy, safety, and tolerability.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder; Benign Prostatic Hyperplasia
• Intervention / Treatment: Drug: doxazosin plus tolterodine SR

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male aged 50 ≤ and ≤ 80 years
• Proven bladder outlet obstruction (BOO, Abrams/Griffith score >20) on urodynamic study

• Symptoms of OAB as verified by the 3 day voiding diary, defined by:

  1. symptoms of urinary urgency (defined as a level of ≥3 in a 5 point urgency scale) at least two episode per 24 hours and
  2. symptoms of urinary frequency (8 micturitions per 24 hours)
• Total International Prostate Symptom Score (IPSS) of 12 or higher
• IPSS quality-of-life (QOL) item score of 3 or higher
• A rating of the bladder condition at Baseline prior to randomization as "Some Moderate Problems", "Severe Problems", or "Many Severe Problems" on the Patient Perception of Bladder Condition (PPBC) questionnaire.
• Ability and willingness to correctly complete the micturition diary and questionnaire
• 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:

• Patients have a baseline post-void residual (PVR) which exceeded 150 mL.
• Any condition that is a contraindication for anticholinergic treatment, including uncontrolled narrow-angled glaucoma, urinary retention or gastric retention.
• Symptomatic acute urinary tract infection (UTI) during the screening period.
• Treatment within the 14 days preceding randomization, or expected to initiate treatment during the study with any anticholinergic drugs and drug treatment for overactive bladder.
• A 5-alpha reductase inhibitor if started less than 3 months prior to screening.
• Patients with previous urethral, prostate or bladder neck surgery.
• Patients with cancer of any type including cancer of the prostate or bladder, uncontrolled medical condition including psychiatric disease or life threatening illness.
• Patients with Parkinson's disease, stroke, multiple sclerosis, spinal cord disease.
• Patients with suspected neurogenic bladder disorder.
• Patients with urethral stricture or bladder neck contracture.
• Serum PSA 4ng/ml (only patients with no malignancy by prostate biopsy can be included).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: doxazosin plus tolterodine SR 2 mg; doxazosin plus tolterodine SR(2 mg, qd) for 12 weeks	Drug: doxazosin plus tolterodine SR; doxazosin plus tolterodine SR(2 mg, qd)for 12 weeks or (4 mg, qd) for 12 weeks; Other Names: Cadura XL 4mg or 8mg; Detrusitol SR 2mg
Experimental: doxazosin plus tolterodine SR 4 mg; doxazosin plus tolterodine SR(4 mg,qd) for 12 weeks	Drug: doxazosin plus tolterodine SR; doxazosin plus tolterodine SR(2 mg, qd)for 12 weeks or (4 mg, qd) for 12 weeks; Other Names: Cadura XL 4mg or 8mg; Detrusitol SR 2mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Numeric change of urgency episodes per 24 hours	12 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in voiding diary parameters	12 weeks of treatment
Change in symptom questionnaires	12 weeks
Patient-Rated Global Assessments of Treatment Benefit, Satisfaction, and Willingness to Continue	12 weeks
Change of uroflowmetry and PVR	12 weeks
Incidence of acute urinary retention	during all study periods

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: June 16, 2009
• First Submitted That Met QC Criteria: June 16, 2009
• First Posted (Estimate): June 17, 2009

Study Record Updates

• Last Update Posted (Actual): December 2, 2019
• Last Update Submitted That Met QC Criteria: November 28, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Overactive bladder; Benign prostate hyperplasia; Doxazosin; Tolterodine
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Prostatic Diseases; Urinary Bladder, Overactive; Prostatic Hyperplasia; Hyperplasia; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Doxazosin; Tolterodine Tartrate
• Other Study ID Numbers: 2008-08-092