Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS in Males With Lower Urinary Tract Symptoms
- Conditions
- Benign Prostatic HyperplasiaLower Urinary Tract Symptoms
- Interventions
- Drug: Placebo tamsulosin hydrochloride OCAS 0.4 mgDrug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mgDrug: Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg
- Registration Number
- NCT01018511
- Lead Sponsor
- Astellas Pharma Europe B.V.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 1334
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FDC 0.4 mg/6 mg tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/6 mg) 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 TOCAS 0.4 mg tamsulosin hydrochloride OCAS 0.4 mg 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 FDC 0.4 mg/9 mg tamsulosin hydrochloride/solifenacin succinate fixed dose combination (0.4 mg/9 mg) 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 Placebo Placebo tamsulosin hydrochloride OCAS 0.4 mg 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 Placebo Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg 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 Placebo Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg 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 TOCAS 0.4 mg Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg 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 TOCAS 0.4 mg Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg 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 FDC 0.4 mg/6 mg Placebo tamsulosin hydrochloride OCAS 0.4 mg 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 FDC 0.4 mg/6 mg Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg 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 FDC 0.4 mg/9 mg Placebo tamsulosin hydrochloride OCAS 0.4 mg 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 FDC 0.4 mg/9 mg Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg 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
- Primary Outcome Measures
Name Time Method Change From Baseline to End of Treatment in Total International Prostate Symptom Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS, Previously Known as Total Urgency Score [TUS]) Baseline and Week 12 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.
- Secondary Outcome Measures
Name Time Method 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 Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours Baseline and Week 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.
Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition Baseline and Week 12 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.
Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition Baseline and Week 12 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.
Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours Baseline and Week 12 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.
Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume Baseline and Week 12 PVR volume is the volume of urine retained after voiding. PVR volume was assessed by ultrasonography or bladder scan.
Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours Baseline and Week 12 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.
Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours Baseline and Week 12 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.
Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours Baseline and Week 12 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.
Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours Baseline and Week 12 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.
Change From Baseline to End of Treatment in IPSS Voiding Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in IPSS Storage Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in IPSS QoL Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in Individual IPSS Scores Baseline and Week 12 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.
Change From Baseline to End of Treatment in Symptom Bother Score Baseline and Week 12 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.
Change From Baseline to End of Treatment in Health Related QoL (HRQoL) Subscale: Coping Score Baseline and Week 12 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.
Change From Baseline to End of Treatment in HRQoL Subscale: Concern Score Baseline and Week 12 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.
Change From Baseline to End of Treatment in HRQoL Subscale: Sleep Score Baseline and Week 12 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.
Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) Baseline and Week 12 Qmax during a micturition (urination) was recorded using uroflowmetry.
Change From Baseline to End of Treatment in Average Flow Rate (Qmean) Baseline and Week 12 Qmean during a micturition (urination) was recorded using uroflowmetry.
Change From Baseline to End of Treatment in HRQoL Subscale: Social Score Baseline and Week 12 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.
Change From Baseline to End of Treatment in HRQoL Subscale: Total Score Baseline and Week 12 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.
Percentage of Participants Who Were OAB-q Responders at End of Treatment Week 12 (end of treatment) A OAB-q responder was defined as a participant with an improvement from baseline in HRQoL subscale total score ≥ 10.
Change From Baseline to End of Treatment in EQ-5D Mobility Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in EQ-5D Self-care Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Baseline and Week 12 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).
Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score Baseline and Week 12 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).
Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms Baseline and Week 12 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).
Patient Global Impression Scale at End of Treatment: General Health Baseline and Week 12 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).
Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms Baseline and Week 12 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).
Number of Participants With Adverse Events (AEs) From first dose of double-blind study drug up to 14 days of last dose of double-blind study drug (up to 14 weeks) 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.
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)