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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Lower Urinary Tract Symptoms, Bladder Outlet Obstruction

Intervention / Treatment
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* Drug: solifenacin succinate
* Drug: tamsulosin hydrochloride
* Drug: Placebo to solifenacin
* Drug: Placebo to tamsulosin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received once daily, oral doses of placebo matching solifenacin succinate and tamsulosin tablets for 12 weeks. | Drug: Placebo to solifenacin<br> <br> Drug: Placebo to tamsulosin<br> <br> |
| Experimental: 6 mg Solifenacin + 0.4 mg Tamsulosin<br>Participants received once daily, oral doses of 6 mg solifenacin succinate and 0.4 mg tamsulosin tablets for 12 weeks. | Drug: solifenacin succinate<br>* Solifenacin succinate tablets<br>* Other names: VESIcare;Drug: tamsulosin hydrochloride<br>* Tamsulosin hydrochloride Oral Control Absorption System (TOCAS) tablets<br>* Other names: Flomax CR;|
| Experimental: 9 mg Solifenacin + 0.4 mg Tamsulosin<br>Participants received once daily, oral doses of 9 mg solifenacin succinate and 0.4 mg tamsulosin tablets for 12 weeks. | Drug: solifenacin succinate<br>* Solifenacin succinate tablets<br>* Other names: VESIcare;Drug: tamsulosin hydrochloride<br>* Tamsulosin hydrochloride Oral Control Absorption System (TOCAS) tablets<br>* Other names: Flomax CR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax) | 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) | 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) | 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) | 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) | 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 | 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) | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lower Urinary Tract Symptoms, Bladder Outlet Obstruction, Treatment, Solifenacin Succinate, Tamsulosin hydrochloride