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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00507455
First received: July 25, 2007
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Lower Urinary Tract Symptoms
Bladder Outlet Obstruction
Drug: solifenacin succinate
Drug: tamsulosin hydrochloride
Drug: Placebo to solifenacin
Drug: Placebo to tamsulosin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Post Void Residual Volume (PVR) [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline to End of Treatment in Bladder Contractility Index (BCI) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline to End of Treatment in Percent Bladder Voiding Efficiency (BVE) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    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.


  • 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). ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in International Prostate Symptoms Score (IPSS) [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in IPSS Voiding Score [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in IPSS Storage Score [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Patient Perception of Bladder Condition (PPBC) [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Number of Micturitions Per 24 Hours [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Number of Urgency Episodes Per 24 Hours [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Number of Incontinence Episodes Per 24 Hours [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Volume Voided Per Micturition [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in ICIQ-MLUTS Total Symptom Bother Score [ Time Frame: Baseline and Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in ICIQ-LUTSqol Overall Symptom Interference of Life Score [ Time Frame: Baseline and Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.



Enrollment: 222
Study Start Date: June 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507455

  Show 33 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Use Central Contact Astellas Pharma US, Inc.
  More Information

Publications:
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00507455     History of Changes
Other Study ID Numbers: 905-CL-058, 2007-001268-57
Study First Received: July 25, 2007
Results First Received: July 14, 2014
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
European Union: European Medicines Agency

Keywords provided by Astellas Pharma Inc:
Lower Urinary Tract Symptoms
Bladder Outlet Obstruction
Treatment
Solifenacin Succinate
Tamsulosin hydrochloride

Additional relevant MeSH terms:
Urinary Bladder Neck Obstruction
Lower Urinary Tract Symptoms
Urethral Obstruction
Urethral Diseases
Urologic Diseases
Urinary Bladder Diseases
Urological Manifestations
Signs and Symptoms
Tamsulosin
Solifenacin
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on August 26, 2014