Solifenacin Succinate With Tamsulosin HCl in Males With Lower Urinary Tract Symptoms and Bladder Outlet Obstruction

July 14, 2014 updated by: Astellas Pharma Inc

A Phase 2, Randomized, Double-Blind, Parallel Group, Placebo Controlled, Multi-Center Study to Evaluate the Safety of the Co-administration of Solifenacin Succinate With 0.4 mg Tamsulosin Hydrochloride OCAS (TOCAS) Using Urodynamics in Male Subjects With Lower Urinary Tract Symptoms (LUTS) and Bladder Outlet Obstruction (BOO)

A study to evaluate the safety of the co-administration of solifenacin succinate with tamsulosin hydrochloride in men with lower urinary tract symptoms (LUTS) and bladder outlet obstruction (BOO).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

222

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Edegem, Belgium, 2650
      • Kortrijk, Belgium
  • Czech Republic
      • Olomouc, Czech Republic
      • Pilsen, Czech Republic
      • Prague, Czech Republic
  • Germany
      • Aachen, Germany
      • Hagenow, Germany
      • Landshut, Germany
      • Muelheim, Germany
  • Hungary
      • Budapest, Hungary
      • Szeged, Hungary
      • Szekszard, Hungary
  • Poland
      • Bialystok, Poland
      • Myslowice, Poland
      • Szczecin, Poland
      • Warszawa, Poland
  • United States
    • Alabama
      • Homewood, Alabama, United States, 35209
    • California
      • La Mesa, California, United States, 91942
      • Long Beach, California, United States, 90806
      • San Bernardino, California, United States, 92404
      • San Diego, California, United States, 92108
    • Connecticut
      • Middlebury, Connecticut, United States, 06762
    • Florida
      • New Port Richey, Florida, United States, 34655
    • Idaho
      • Coeur d'Alene, Idaho, United States, 83814
    • Iowa
      • Des Moines, Iowa, United States, 50309
      • Iowa City, Iowa, United States, 52242
    • Massachusetts
      • Watertown, Massachusetts, United States, 02472
    • Nevada
      • Las Vegas, Nevada, United States, 89148
    • New York
      • New York, New York, United States, 10021
    • North Carolina
      • Greensboro, North Carolina, United States, 27403
    • Texas
      • Austin, Texas, United States, 78705
      • San Antonio, Texas, United States, 78229
    • Virginia
      • Charlottesville, Virginia, United States, 22908

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

41 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Diagnosed with Lower Urinary Tract Symptoms (LUTS) and Bladder Outlet Obstruction (BOO)
  • BOO indication by a Bladder Outlet Obstruction Index (BOOI) ≥ 20
  • Patient has a total International Prostate Symptom Score (IPPS) score of ≥ 8 (Inclusion criteria for Baseline also)
  • Patient had a maximum urinary flow rate of ≤ 12 mL/sec, with a voided volume of ≥ 120 mL during free flow in a representative assessment of uroflowmetry.

Exclusion Criteria:

  • History of urinary retention in preceding 12 months
  • Current urinary tract infection (UTI) or symptomatic and recurrent UTI of > 3 episodes within 12 months.
  • Known clinical history or diagnosis of chronic inflammation, stone in bladder or ureter, or other causes of outflow tract obstruction
  • Known diagnosis or history of carcinoma or previous pelvic radiation therapy, except non-metastatic basal or squamous cell carcinoma of the skin that had been treated successfully
  • Clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to Visit 1

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Participants received once daily, oral doses of placebo matching solifenacin succinate and tamsulosin tablets for 12 weeks.
Drug: Placebo to solifenacin
Drug: Placebo to tamsulosin
Experimental: 6 mg Solifenacin + 0.4 mg Tamsulosin
Participants received once daily, oral doses of 6 mg solifenacin succinate and 0.4 mg tamsulosin tablets for 12 weeks.
Drug: solifenacin succinate
Solifenacin succinate tablets
Other Names:
  • YM905
  • VESIcare
Drug: tamsulosin hydrochloride
Tamsulosin hydrochloride Oral Control Absorption System (TOCAS) tablets
Other Names:
  • Omnic Ocas
  • Flomax CR
Experimental: 9 mg Solifenacin + 0.4 mg Tamsulosin
Participants received once daily, oral doses of 9 mg solifenacin succinate and 0.4 mg tamsulosin tablets for 12 weeks.
Drug: solifenacin succinate
Solifenacin succinate tablets
Other Names:
  • YM905
  • VESIcare
Drug: tamsulosin hydrochloride
Tamsulosin hydrochloride Oral Control Absorption System (TOCAS) tablets
Other Names:
  • Omnic Ocas
  • Flomax CR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax)
Time Frame: Baseline and Week 12
Detrusor pressure (Pdet) measures the force the detrusor muscle is exerting. This pressure is required to expel urine from the bladder during normal voiding. A high detrusor pressure may be observed in the presence of outflow tract obstruction. Detrusor pressure at maximum urinary flow rate (PdetQmax) was evaluated using simultaneous recording of urinary voiding by an uroflowmeter during detrusor pressure evaluation by cystometry.
Baseline and Week 12
Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax)
Time Frame: Baseline and Week 12
The maximum flow rate (Qmax) during a micturition (urination) was recorded using uroflowmetry. A reduction in maximum flow rate may be due to an obstruction of the bladder outlet or a failure of the detrusor muscle to aid in expelling urine.
Baseline and Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Post Void Residual Volume (PVR)
Time Frame: Baseline and Weeks 2, 4, 8 and 12

Healthy micturitions result in complete emptying of the bladder. Post Void Residual (PVR) is the volume of urine retained after voiding (post-void residual urine). Post void residual volume was assessed by abdominal ultrasound. An increasing PVR over time is an indicator of abnormal bladder function or detrusor decompensation.

End-of-treatment is the last post-baseline assessment during the treatment period.

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline to End of Treatment in Bladder Contractility Index (BCI)
Time Frame: Baseline and Week 12

The Bladder Contractility Index (BCI) is a value used to measure the degree of contractility. BCI was calculated using the following formula:

BCI = pdetQmax + 5Qmax.

Strong contractility is a BCI > 150, normal contractility is a BCI of 100-150 and weak contractility is a BCI of < 100.

LS means were adjusted for pooled center and Baseline value.
Baseline and Week 12
Change From Baseline to End of Treatment in Percent Bladder Voiding Efficiency (BVE)
Time Frame: Baseline and Week 12

Percent Bladder Voiding Efficiency (BVE) is a product of bladder contractility against the urethral resistance and is measured according to the degree of bladder emptying. BVE is expressed as a percentage and is calculated using the formula:

Bladder Voiding efficiency = (Voided volume x 100)/maximum cystometric capacity.

A higher number indicates a higher voiding efficiency.

LS means were adjusted for pooled center and Baseline value.
Baseline and Week 12
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests
Time Frame: From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks).
Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as mild (no disruption of normal daily activities), moderate (affected normal daily activities) or severe (inability to perform daily activities) and for causal relationship to study drug.
From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks).
Change From Baseline in International Prostate Symptoms Score (IPSS)
Time Frame: Baseline and Weeks 2, 4, 8 and 12

The IPSS is a validated global questionnaire used to assess the degree of "bother" from benign prostatic hyperplasia symptoms and is based on the answers to 7 questions concerning urinary symptoms:

  • Sensation of incomplete emptying
  • Repeat urinating after 2 hours (frequency)
  • Start and stop several times (intermittency)
  • Urgency
  • Weak stream
  • Straining
  • Nocturia

Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in IPSS Voiding Score
Time Frame: Baseline and Weeks 2, 4, 8 and 12

The IPSS is a validated global questionnaire used to assess the degree of "bother" from benign prostatic hyperplasia symptoms based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The voiding score is the sum of the responses to 4 questions relating to urination (incomplete emptying, intermittency, weak stream and straining) and ranges from 0 to 20 (asymptomatic to very symptomatic).

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in IPSS Storage Score
Time Frame: Baseline and Weeks 2, 4, 8 and 12

The IPSS is a validated global questionnaire used to assess the degree of "bother" from benign prostatic hyperplasia symptoms based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The storage symptom score is the sum of the responses to 3 questions relating to storage symptoms (frequency, urgency and nocturia) and ranges from 0 to 15 (asymptomatic to very symptomatic).

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Patient Perception of Bladder Condition (PPBC)
Time Frame: Baseline and Weeks 2, 4, 8 and 12

The patient perception of bladder condition (PPBC) questionnaire asks participants to assess their bladder condition using a 6-point validated Likert scale which ranges from 1 (does not cause me any problems at all) to 6 (causes me many severe problems).

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Number of Micturitions Per 24 Hours
Time Frame: Baseline and Weeks 2, 4, 8 and 12

A micturition is any voluntary urination, excluding episodes of incontinence only. The mean number of micturitions per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Number of Urgency Episodes Per 24 Hours
Time Frame: Baseline and Weeks 2, 4, 8 and 12

For each micturition and/or incontinence episode participants rated the degree of associated urgency (the sudden compelling desire to pass urine, which is difficult to defer) according to the following scale: 0: No Urgency, felt no need to empty my bladder but did so for another reason; 1: Mild urgency, could postpone passing water for as long as necessary; 2: Moderate urgency, could postpone passing water for a short while; 3: Severe urgency, could not postpone passing water; 4: Urge incontinence, leaked before reaching the toilet. An urgency episode is defined as an episode with urgency severity of three or higher.

The mean number of urgency episodes per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Number of Incontinence Episodes Per 24 Hours
Time Frame: Baseline and Weeks 2, 4, 8 and 12

The mean number of incontinence episodes (the involuntary leakage of urine) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Volume Voided Per Micturition
Time Frame: Baseline and Weeks 2, 4, 8 and 12

The mean volume voided per micturition was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in International Consultation on Incontinence Questionnaire - Male Lower Urinary Tract Symptom (ICIQ MLUTS) Total Symptom Score
Time Frame: Baseline and Weeks 4, 8 and 12

Male lower urinary tract symptoms were assessed by the ICIQ MLUTS questionnaire which consists of 13 questions regarding urinary symptoms. Each question is answered by the participant on a scale from 0 (never) to 4 (all the time). The total symptom score ranges from 0 to 52, where larger scores correspond to worse conditions.

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 4, 8 and 12
Change From Baseline in ICIQ-MLUTS Total Symptom Bother Score
Time Frame: Baseline and Weeks 4, 8 and 12

The degree to which urinary symptoms bothered participants was assessed by the ICIQ MLUTS questionnaire which consists of 13 symptom bother questions. Each question is answered by the participant on a scale from 0 (not at all) to 10 (a great deal). The total bother score ranges from 0 to 130, where larger scores correspond to worse outcomes.

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 4, 8 and 12
Change From Baseline in International Consultation on Incontinence Questionnaire - Lower Urinary Tract Symptom Quality of Life (ICIQ-LUTSqol) Symptom Score
Time Frame: Baseline and Weeks 4, 8 and 12

Quality of life was assessed by the ICIQ-LUTSqol questionnaire which consists of 19 questions regarding daily activities affected by urinary problems. Participants responded to each question on a scale from 1 (not at all) to 4 (a lot). The total symptom score ranges from 19 to 76, where larger scores correspond to a lesser quality of life).

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 4, 8 and 12
Change From Baseline in ICIQ-LUTSqol Overall Symptom Interference of Life Score
Time Frame: Baseline and Weeks 4, 8 and 12

Participants were asked to rate how much their urinary symptoms interfered overall with their everyday life on a scale from 0 (not at all) to 10 (a great deal).

Least squares (LS) means were adjusted for pooled center and the Baseline value.
Baseline and Weeks 4, 8 and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Astellas Pharma Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Actual)

August 1, 2008

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

July 25, 2007

First Submitted That Met QC Criteria

July 25, 2007

First Posted (Estimate)

July 26, 2007

Study Record Updates

Last Update Posted (Estimate)

August 6, 2014

Last Update Submitted That Met QC Criteria

July 14, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 905-CL-058
  • 2007-001268-57 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe