Efficacy and Safety of Alfuzosin for the Treatment of Voiding Dysfunction in Female

Efficacy and Safety of Alfuzosin for the Treatment of Non-neurogenic Voiding Dysfunction in Female: An 8 Week Prospective, Randomized Double Blind, Placebo-Controlled, Parallel Group Study (Phase Ⅱ)

The purpose of this study is to explore the efficacy of Alfuzosin (10 mg, qd) in reducing the score of International Prostate Symptom Score (IPSS) from baseline to 8 weeks of treatment in female patients with voiding dysfunction.

Study Overview

• Status: Completed
• Conditions: Voiding Dysfunction
• Intervention / Treatment: Drug: alfuzosin hydrochloride XL 10mg; Drug: Placebo

Detailed Description

Trial design

Phase II, multi-center, randomized, double-blind, placebo-controlled, parallel group study to evaluate the clinical efficacy and safety of alfuzosin (10mg, qd) from baseline to 8 weeks of treatment in female patients with non-neurogenic voiding dysfunction.

Efficacy Assessment

1. Primary efficacy endpoint

   Actual change in the score of IPSS from baseline to 8 weeks of treatment.

2. Secondary efficacy endpoint

   • IPSS parameters
   • Percent change in the score of IPSS from baseline to 4 and 8 weeks of treatment.
   • Actual and percent changes in the sub-scale of IPSS from baseline to 4 and 8 weeks of treatment
   • Storage score: sum of questions 2, 4 and 7
   • Voiding score: sum of questions 1, 3, 5 and 6
   • Scored form of the Bristol Female Lower Urinary Tract Symptoms (BFLUTS-SF)parameters
   • Actual and Percent change in BFLUTS-SF from baseline to 4 and 8 weeks of treatment.

   • Actual and percent changes in the sub-scale of BFLUTS-SF from baseline to 4 and 8 weeks of treatment

     • BFLUTS-FS: sum scores F1-F4
     • BFLUTS-VS: sum scores V1-V3
     • BFLUTS-IS: sum scores I1-I5
     • BFLUTS-sex: sum scores S1 & S2

   • Uroflowmetry & PVR parameters

     • Numeric and percent changes from baseline to 4 and 8 weeks of treatment.
     • Maximum flow rate (mL/s)
     • Average flow rate (mL/s)
     • Post-void residual urine (mL)
     • Micturition diary parameters
     • Change in mean number of micturitions per 24 hours at weeks 4 and 8 relative to baseline
     • Percent change of micturitions per 24 hours at weeks 4 and 8 relative to baseline
     • Change in mean number of nighttime micturitions per 24 hours at weeks 4 and 8 relative to baseline
     • Percent change of nighttime micturitions per 24 hours at weeks 4 and 8 relative to baseline
     • Change in mean number of urgency episodes per 24 hours at weeks 4 and 8 relative to baseline (Urgency episodes are defined as those with Bladder Sensation Scale rating of ≥ 3 in the diary).
     • Percent change of urgency episodes per 24 hours at weeks 4 and 8 relative to baseline
     • Change in the mean and sum rating on the Bladder Sensation Scale at weeks 4 and 8 relative to baseline
     • Quality of life (QoL) parameters
     • Change in Bother score of IPSS from baseline to 4 and 8 weeks of treatment.
     • Change in QOL subscale scores of BFLUTS SF from baseline to 4 and 8 weeks of treatment
     • BFLUTS-QoL: Sum scores QoL1-QoL5
     • Patient Perception of Bladder Condition (PPBC)
     • Change from baseline in PPBC after 8 weeks of double-blind treatment
     • Benefit, Satisfaction, and Willingness to Continue (BSW) Questions
     • Patient Perception of Treatment Benefit at week 8
     • Patient Perception of Treatment Satisfaction at week 8
     • Willingness to continue with treatment at week 8

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital
  • Kyonggi-do, Korea, Republic of, 420-717
    • Holy Family Hospital, The Catholic University of Korea
  • Pusan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 137-701
    • Kangnam St. Mary's Hospital, The Catholic University of Korea
  • Seoul, Korea, Republic of, 100-380
    • Cheil General Hospital & Women's Healthcare Center, College of Medicine, Kwandong University
  • Seoul, Korea, Republic of, 136-705
    • Anam Hospital, College of Medicine, Korea University
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center, Ulsan College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female aged ≥ 18
• Have voiding symptoms as chief complaints over 3 months
• IPSS symptom score ≥ 15
• A peak flow rate <12 mL/sec with a minimum voided volume of 100 mL and/or a postvoid residual urine volume >150 mL
• Underwent pressure-flow study

Exclusion Criteria:

• Patients who meet any of the following criteria are to be excluded from the study:
• Neurogenic voiding dysfunction
• Anatomic causes of bladder outlet obstruction
• Perform physical examination in patients diagnosed as BOO in pressure-flow study by urethral evaluation with 16 Fr urethral sound: if there is resistance to 16Fr sound, it will be diagnosed as anatomical BOO and the patients can not participate in the study.
• Previous surgical procedures related to incontinence or cystocele
• Pregnant or nursing women
• Intake of medications and drugs affecting bladder function: alpha blocker, anticholinergic
• Anticholinergic drugs: Tolterodine, Oxybutynin, Propiverin, Trospium, Solifenacin, SSRI including TCA
• Cholinergic drug: Bethanechol
• Any other blocker other than alfuzosin
• patients can be enrolled after wash-out
• Any positive urine culture had to be successfully treated before the recruitment.
• Clinically significant ( ≥ Stamey grade II/III) stress incontinence as determined by the investigator and confirmed for female patients by a cough provocation test.
• Recurrent UTIs defined as having been treated for symptomatic UTIs ≥ 4 times in the last year
• Diagnosed or suspected interstitial cystitis
• Patients with marked cystocele or other clinically significant pelvic prolapse.
• Treatment within the 14 days preceding randomization, or expected to initiate treatment during the study with:
• Estrogen treatment started more than 2 months prior to inclusion will be allowed
• Receipt of any electrostimulation or bladder training within the 14 days before randomization, or expected to start such treatment during the study.
• Hypersensitive to the study drug
• Orthotopic hypotension or history of orthotopic hypotension
• Intake of calcium channel blockers
• Severe hepatic or renal dysfunctions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; One tablet to be taken daily after a meal before bedtime for 8 weeks.
EXPERIMENTAL: Alpha blocker; alfuzosin hydrochloride XL 10mg	Drug: alfuzosin hydrochloride XL 10mg; One tablet to be taken daily after a meal before bedtime for 8 weeks.; Other Names: Xatral® XL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Actual change in the score of IPSS from baseline to 8 weeks of treatment.	8 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
IPSS parameters	4 and 8 weeks of treatment.
BFLUTS-SF parameters	4 and 8 weeks of treatment
Uroflowmetry & PVR parameters	4 and 8 weeks of treatment
Micturition diary parameters	4 and 8 weeks of treatment
Quality of life parameters	4 and 8 weeks of treatment
Patient Perception of Bladder Condition	8 weeks of treatment
Benefit, Satisfaction, and Willingness to Continue (BSW) Questions	8 weeks of treatment

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Handok Inc.; The Korean Urological Association

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): March 1, 2009
• Study Completion (ACTUAL): December 1, 2009

Study Registration Dates

• First Submitted: May 14, 2008
• First Submitted That Met QC Criteria: May 15, 2008
• First Posted (ESTIMATE): May 16, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): June 10, 2013
• Last Update Submitted That Met QC Criteria: June 7, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: female voiding dysfunction; alpha adrenoreceptor antagonists; IPSS or American Urological Association symptom index
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Alfuzosin
• Other Study ID Numbers: 2007-07-073