Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS in Males With Lower Urinary Tract Symptoms

Study Overview
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Brief Summary
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Clinical study to examine the efficacy, safety and tolerability of combination therapy of tamsulosin hydrochloride and solifenacin succinate compared to monotherapy of tamsulosin hydrochloride in the treatment of males with LUTS associated with BPH with a substantial storage component.

Official Title
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A Randomized, Double-blind, Parallel Group, Placebo Controlled, Multi-center Study of Fixed Dose Combinations of Solifenacin Succinate (6 mg and 9 mg) With Tamsulosin Hydrochloride OCAS 0.4 mg and Tamsulosin Hydrochloride OCAS 0.4 mg Monotherapy, in Male Subjects With Lower Urinary Tract Symptoms (LUTS) Associated With Benign Prostatic Hyperplasia (BPH) With a Substantial Storage Component

Conditions
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Benign Prostatic Hyperplasia, Lower Urinary Tract Symptoms

Intervention / Treatment
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* Drug: Placebo tamsulosin hydrochloride OCAS 0.4 mg
* Drug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg
* Drug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg
* Drug: tamsulosin hydrochloride OCAS 0.4 mg
* Drug: tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/6 mg)
* Drug: tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/9 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voiding and storage symptoms diagnosed as LUTS associated with BPH for ≥ 3 months A total International Prostate Symptom Score (IPSS) of ≥13 A maximum urinary flow rate of ≥4.0 mL/s and ≤12.0 mL/s, with voided volume of ≥120 mL during free flow A micturition frequency of ≥8 and at least 2 episodes of urgency with Patient Perception of the Intensity of Urgency Scale grade 3 or 4 per day on average on the 3 day micturition diary (at randomization) Exclusion Criteria: Any significant Post Void Residual volume (>150 mL) A prostate with estimated weight ≥75 ml as assessed by transvesical or transrectal ultrasound Evidence of a symptomatic urinary tract infection

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received 3 tablets once a day for 12 weeks. Placebo tamsulosin hydrochloride oral controlled absorption system (OCAS) 0.4 mg tablet; Placebo fixed dose combination (FDC) tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg tablet | Drug: Placebo tamsulosin hydrochloride OCAS 0.4 mg<br>* tablet<br>Drug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg<br>* tablet<br>Drug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg<br>* tablet<br>|
| Active Comparator: TOCAS 0.4 mg<br>Participants received 3 tablets once a day for 12 weeks. Tamsulosin hydrochloride OCAS (TOCAS) 0.4 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg tablet | Drug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg<br>* tablet<br>Drug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg<br>* tablet<br>Drug: tamsulosin hydrochloride OCAS 0.4 mg<br>* tablet<br>* Other names: YM617;|
| Experimental: FDC 0.4 mg/6 mg<br>Participants received 3 tablets once a day for 12 weeks. Placebo TOCAS 0.4 mg tablet; FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg tablet | Drug: Placebo tamsulosin hydrochloride OCAS 0.4 mg<br>* tablet<br>Drug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg<br>* tablet<br>Drug: tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/6 mg)<br>* tablet<br>* Other names: EC905;|
| Experimental: FDC 0.4 mg/9 mg<br>Participants received 3 tablets once a day for 12 weeks. Placebo TOCAS 0.4 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg tablet; FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg tablet | Drug: Placebo tamsulosin hydrochloride OCAS 0.4 mg<br>* tablet<br>Drug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg<br>* tablet<br>Drug: tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/9 mg)<br>* tablet<br>* Other names: EC905;|

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 Total International Prostate Symptom Score | The International Prostate Symptom Score (IPSS) is a validated global questionnaire to assess the degree of urinary symptoms, based on answers to 7 questions concerning urinary symptoms: Incomplete emptying of the bladder Intermittency Weak stream Hesitancy Frequency Urgency Nocturia Each question is assigned points from 0 to 5 indicating increasing severity of the symptom. Total score can range from 0 to 35 (mildly symptomatic to severely symptomatic). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS, Previously Known as Total Urgency Score [TUS]) | The Patient Perception of the Intensity of Urgency Scale (PPIUS) is a validated scale completed as part of the micturition diary. For each micturition and/or incontinence episode, the participant rated the degree of associated urgency according to the following 5-point categorical scale: 0. No urgency; 1. Mild urgency; 2. Moderate urgency; 3. Severe urgency; 4. Urgency incontinence TUFS was calculated as the sum of the PPIUS gradings from the 3-day diary divided by the number of days on which urgency grading was recorded. Higher scores indicate more severe urgency. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Treatment in Mean 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. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition | A micturition is any voluntary urination, excluding episodes of incontinence only. 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. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition | A micturition is any voluntary urination, excluding episodes of incontinence only. The maximum volume voided per micturition was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours | An urgency episode is defined as an episode of strong desire to void accompanied by fear of leakage or pain. The mean number of urgency episodes with PPIUS grade 3 (Severe urgency) or 4 (Urgency incontinence) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours | An urgency incontinence episode is defined as an episode with any involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes with PPIUS grade 3 (Severe incontinence) or 4 (Urgency incontinence) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | An incontinence episode is defined as an episode with any involuntary loss of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours | A nocturia episode is defined as waking up at night to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the patient gets up in the morning with the intention to stay awake). The mean number of nocturia episodes per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours | The mean number of pads per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in IPSS Voiding Score | The IPSS is a validated global questionnaire to assess the degree of urinary symptoms based on answers to 7 questions. 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 voiding questions (incomplete emptying of the bladder, intermittency, weak stream, hesitancy) and ranges from 0 to 20 (mildly symptomatic to severely symptomatic). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in IPSS Storage Score | The IPSS is a validated global questionnaire to assess the degree of urinary symptoms based on 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 storage questions (frequency, urgency and nocturia) and ranges from 0 to 15 (mildly symptomatic to severely symptomatic). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in IPSS QoL Score | The QoL assessment was a single question asking the participant how he would feel about tolerating his current level of symptoms for the rest of his life. The answers ranged from 0 to 6 (delighted to terrible). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Individual IPSS Scores | The IPSS is a validated global questionnaire to assess the degree of urinary symptoms, based on answers to 7 questions concerning urinary symptoms: Incomplete emptying of the bladder Intermittency Weak stream Hesitancy Frequency Urgency Nocturia Each question is assigned points from 0 to 5 indicating increasing severity of the symptom. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Symptom Bother Score | The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The Symptom Bother portion consists of an 8-item scale scored from 1 to 6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from baseline indicates an improvement. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Health Related QoL (HRQoL) Subscale: Coping Score | The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: coping concern sleep social interaction Coping score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in HRQoL Subscale: Concern Score | The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: coping concern sleep social interaction Concern score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in HRQoL Subscale: Sleep Score | The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: coping concern sleep social interaction Sleep score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in HRQoL Subscale: Social Score | The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: coping concern sleep social interaction Social score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in HRQoL Subscale: Total Score | The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: coping concern sleep social interaction Total score is calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. | Baseline and Week 12 | 
| Percentage of Participants Who Were OAB-q Responders at End of Treatment | A OAB-q responder was defined as a participant with an improvement from baseline in HRQoL subscale total score ≥ 10. | Week 12 (end of treatment) | 
| Change From Baseline to End of Treatment in EQ-5D Mobility Score | The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: mobility self-care usual activity pain/discomfort anxiety/depression Each domain has 3 response levels (1= no problem, 2= some problems, 3 = confined to bed). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in EQ-5D Self-care Score | The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: mobility self-care usual activity pain/discomfort anxiety/depression Each domain has 3 response levels (1= no problem, 2= some problems, 3 = unable to wash/dress). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: mobility self-care usual activity pain/discomfort anxiety/depression Each domain has 3 response levels (1= no problem, 2= some problems, 3 = unable to perform usual activities). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: mobility self-care usual activity pain/discomfort anxiety/depression Each domain has 3 response levels (1= no pain, 2= moderate pain, 3 = extreme pain). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: mobility self-care usual activity pain/discomfort anxiety/depression Each domain has 3 response levels (1= not anxious, 2= moderately anxious, 3 = extremely anxious). | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score | Visual Analogue Scale (VAS) is part of the EQ-5D questionnaire. The VAS is self-rated by the participant ranging from 0 to 100 (worst imaginable health state to best imaginable health state). | Baseline and Week 12 | 
| Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | The Patient Global Impression (PGI) is a global questionnaire completed by the participant to assess both the change in the participants overall condition and the change in bladder symptoms since the start of the study. The questionnaire consists of 2 questions with 7 response levels ranging from 1 to 7 (very much improved to very much worse). | Baseline and Week 12 | 
| Patient Global Impression Scale at End of Treatment: General Health | The Patient Global Impression (PGI) is a global questionnaire completed by the participant to assess both the change in the participants overall condition and the change in bladder symptoms since the start of the study. The questionnaire consists of 2 questions with 7 response levels ranging from 1 to 7 (very much improved to very much worse). | Baseline and Week 12 | 
| Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | The Clinician Global Impression (CGI) is a questionnaire completed by the physician to assess change in the participants bladder symptoms since the start of the study. The questionnaire consists of 1 question with 7 response levels ranging from 1 to 7 (very much improved to very much worse). | Baseline and Week 12 | 
| Number of Participants With Adverse Events (AEs) | Safety is monitored by collecting AEs, which include abnormal laboratory parameters, vital signs or ECG data if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE (SAE) 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. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred after administration of the first dose of double-blind study drug until 14 days after the last dose of double-blind study drug. | From first dose of double-blind study drug up to 14 days of last dose of double-blind study drug (up to 14 weeks) | 
| Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume | PVR volume is the volume of urine retained after voiding. PVR volume was assessed by ultrasonography or bladder scan. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | Qmax during a micturition (urination) was recorded using uroflowmetry. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Average Flow Rate (Qmean) | Qmean during a micturition (urination) was recorded using uroflowmetry. | Baseline and Week 12 | 
| Apparent Clearance (CL/F) of Tamsulosin |  | Week 4, Week 8 and Week 12 | 
| Maximum Concentration at Steady State (Cmaxss) of Tamsulosin |  | Week 4, Week 8 and Week 12 | 
| Minimum Concentration at Steady State (Cminss) of Tamsulosin |  | Week 4, Week 8 and Week 12 | 
| Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin |  | Week 4, Week 8 and Week 12 | 
| Area Under the Curve at Steady State (AUCss) of Tamsulosin |  | Week 4, Week 8 and Week 12 (collection time points: trough, 1-3 hours post dose, 4-5 hours post-dose and 7-10 hours post-dose) | 
| CL/F of Solifenacin |  | Week 4, Week 8 and Week 12 | 
| Cmaxss of Solifenacin |  | Week 4, Week 8 and Week 12 | 
| Cminss of Solifenacin |  | Week 4, Week 8 and Week 12 | 
| Tmaxss of Solifenacin |  | Week 4, Week 8 and Week 12 | 
| AUCss of Solifenacin |  | Week 4, Week 8 and Week 12 (collection time points: trough, 1-3 hours post dose, 4-5 hours post-dose and 7-10 hours post-dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EC905, Solifenacin succinate, Tamsulosin hydrochloride OCAS, Treatment, Benign Prostatic Hyperplasia, Vesomni, Lower Urinary Tract Symptoms