A Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Men With OAB Symptoms While Taking Tamsulosin Hydrochloride for Lower Urinary Tract Symptoms (LUTS) Due to Benign Prostatic Hyperplasia (BPH)
- Conditions
- Benign Prostatic HyperplasiaOveractive Bladder
- Interventions
- Registration Number
- NCT02757768
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
The purpose of the study was to assess the efficacy, safety, and tolerability of mirabegron versus placebo in men with overactive bladder (OAB) symptoms while taking tamsulosin hydrochloride for lower urinary tract symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH).
- Detailed Description
At Screening (Visit 1), participants entered into a 4-week open label tamsulosin hydrochloride 0.4 mg QD run-in period prior to being randomized into the 12-week double-blind treatment period (Visit 2). At conclusion of the 4-week tamsulosin hydrochloride run-in period, participants completed a 3-day diary just prior to Baseline (Visit 2). Approximately 7 days prior to Visit 2 participants received a phone call reminding them about the diary and to answer any questions.
If participants met all entry criteria at the end of the tamsulosin hydrochloride run-in period, participants were randomized to 1 of 2 treatment groups (mirabegron or placebo) for 12 weeks of treatment in addition to the continuation of tamsulosin hydrochloride 0.4 mg QD. Those participants randomized to Mirabegron started at 25 mg and increased to 50 mg after 4 weeks. Those participants randomized to placebo started blinded product matched to the mirabegron 25 mg tablet and increased to blinded product matched to 50 mirabegron after 4 weeks. Once a participant increased dose, the participant remained on that dose for the remainder of the study unless for safety reasons was required to discontinue study drug.
A training diary was completed in the first 2 weeks of the tamsulosin hydrochloride run-in period. During this evaluation period at least one telephone contact took place with the participant. Diaries were completed at home, using the electronic patient-reported outcome (ePRO) device, for 3 consecutive days prior to each visit: Baseline (Visit 2), Week 4 (Visit 3), Week 8 (Visit 4), and Week 12/End of Treatment (Visit 5). Site staff contacted the participant approximately 7 days prior to the scheduled visit to remind the participant to complete the electronic diary, review completion instruction and review changes to concomitant medications and adverse events (if applicable).
Three days before Visits 2 (Baseline), 3 (Week 4), 4 (Week 8), and 5 (Week 12), participants completed a 3-day diary, using the ePRO device in which the participant recorded micturition frequency, urgency (PPIUS), incontinence and volume voided. In addition, the diary captured morning and evening blood pressure and pulse rate measurements via Home Blood Pressure Monitoring (HBPM). At Visit 1, International Prostate Symptom Score (IPSS) was completed. At Visits 2, 3, 4, and 5, participants completed the IPSS, EQ-5D-5L, OAB-q, PPBC, and TS-VAS. Maximum urinary flow (Qmax) was measured at Visit 1 (Screening/tamsulosin hydrochloride run-in) and Visit 5 (Week 12/End of Treatment). Post-void residual volume (PVR) was assessed at Screening/tamsulosin hydrochloride run-in (Visit 1), Baseline (Visit 2) and at Week 4 (Visit 3), Week 8 (Visit 4), and Week 12/End of Treatment (Visit 5). A follow-up phone call (Visit 6) was conducted 4-weeks after End of Treatment (Visit 5). Total study participation was approximately 20 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 715
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study. Placebo Tamsulosin Hydrochloride Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study. Mirabegron Mirabegron Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study. Mirabegron Tamsulosin Hydrochloride Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.
- Primary Outcome Measures
Name Time Method Change From Baseline to End of Treatment (EoT) in Mean Number of Micturitions Per Day Baseline and Week 12 Participants recorded micturitions in the e-diary during three days. The mean number of micturitions was calculated as the average number of times a participant recorded a micturition per day during the 3-day period. Only voluntary micturitions were counted and the episodes of incontinence were not included.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Volume Voided Per Micturition Baseline and Weeks 4, 8, and 12 The mean volume voided per micturition during 3 days of the 3-day micturition diary period.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Urgency Incontinence Episodes Per Day Baseline and Weeks 4, 8 and 12 Urgency Incontinence was defined as the complaint of involuntary leakage accompanied by or immediately proceeded by urgency. The mean number of urgency incontinence episodes was calculated as the average number of times a participant recorded an urgency incontinence episode per day during the 3-day micturition diary period.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Coping Score Baseline and Weeks 4, 8, and 12 The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQL). The HRQL portion consists of 25 HRQL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. A higher score on OAB-q HRQL indicated a better response. The lowest and highest possible scores for the Coping subscale ranges from 8 to 48. The Coping score was calculated by adding the 8 response scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Social Interaction Score Baseline and Weeks 4, 8, and 12 The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQL). The HRQL portion consists of 25 HRQL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. A higher score on OAB-q HRQL indicated a better response. The lowest and highest possible scores for the Social Interaction subscale ranges from 5 to 30. The Social Interaction score was calculated by adding the 5 response scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours Baseline and Weeks 4, 8, and 12 A nocturia episode was defined as waking at night one or more time to void (i.e., any voiding associated with sleep disturbance between the date/time the participant goes to bed with the intention to sleep until the date/time the participant gets up in the morning with the intention to stay awake). A night time episode of incontinence is not considered a nocturia episode. The mean number of nocturia episodes per day (24 hours) was calculated as the average number of times a participant recorded a nocturia episode per day during the 3-day micturition diary period.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Treatment Satisfaction Visual Analog Scale (TS-VAS) Baseline and Weeks 4, 8, and 12 The TS-VAS is a visual analog scale that asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) to 100 (Yes, completely).
Change From Baseline to Week 4, Week 8, and Week 12 in Mean Number of Micturitions Per Day Baseline and Weeks 4, 8, and 12 Participants recorded micturitions in the e-diary during three days. The mean number of micturitions was calculated as the average number of times a participant recorded a micturition per day during the 3-day period. Only voluntary micturitions were counted and the episodes of incontinence were not included.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Incontinence Episodes Per Day Baseline and Weeks 4, 8, and 12 An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated as the average number of times a participant recorded an incontinence episode per day during the 3-day micturition diary period.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in International Prostate Symptom Score (IPSS) Total Score Baseline and Weeks 4, 8, and 12 The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Symptom Bother Score Baseline and Weeks 4, 8, and 12 Overactive bladder symptoms were assessed using the Symptom Bother Scale of the Overactive Bladder questionnaire (OAB-q). The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 questions, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). Lower scores on OAB-q symptom bother indicate a better response.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per Day Baseline and Weeks 4, 8, and 12 Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode with a severity of grade 3 or 4, assessed by participants based on the Patient Perception of Intensity of Urgency Scale (PPIUS), where 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The mean number of urgency episodes (grade 3 and/or 4) per day was calculated as the average number of times a participant recorded an urgency episode (grade 3 and/or 4) with or without incontinence per day during the 3-day micturition diary period.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Total Health Related Quality of Life (HRQL) Score Baseline and Weeks 4, 8, and 12 The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was 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 higher score on OAB-q HRQL indicated a better response.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Concern Score Baseline and Weeks 4, 8, and 12 The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQL). The HRQL portion consists of 25 HRQL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. A higher score on OAB-q HRQL indicated a better response. The lowest and highest possible scores for the Concern subscale ranges from 7 to 42. The Concern score was calculated by adding the 7 response scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Voiding Score Baseline and Weeks 4, 8, and 12 The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The subscale voiding score is the sum of the responses to 4 voiding symptoms questions (incomplete emptying, intermittency, weak stream, and straining). The lowest and highest possible scores range from 0 to 20 (mildly symptomatic to severely symptomatic). A higher score is indicative of worse condition and a negative change from baseline indicates an improvement.
Change From Baseline to Week 4, Week 8, Week 12, and EoT in IPSS Subscale Storage Score Baseline and Weeks 4, 8, and 12 The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The subscale storage score is the sum of the responses to 3 storage symptoms questions (frequency, urgency, and nocturia). The lowest and highest possible scores range from 0 to 15 (mildly symptomatic to severely symptomatic). A higher score is indicative of worse condition and a negative change from baseline indicates an improvement.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Quality of Life (QoL) Score Baseline and Weeks 4, 8, and 12 The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). 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 lowest and highest possible score ranges from 0 to 6 (very pleased to terrible). A higher score is indicative of worse condition and a negative change from baseline indicates an improvement.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Sleep Score Baseline and Weeks 4, 8 and 12 The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQL). The HRQL portion consists of 25 HRQL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. A higher score on OAB-q HRQL indicated a better response. The lowest and highest possible scores for the Sleep subscale ranges from 5 to 30. The Sleep score was calculated by adding the 5 response scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in European Quality of Life in 5 Dimensions and 5 Levels (EQ-5D-5L Questionnaire) Utilities Baseline and Weeks 4, 8, and 12 The EQ-5D-5L is an international standardized non-disease specific generic instrument for describing and valuing health status. It has a multidimensional measure of health-related QoL, capable of being expressed as a single index value and specifically designed to complement other health status measures. The EQ-5D-5L has five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels (e.g., 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems/unable to perform the activity). Health-state utility (HSU) data are estimates of the preference for a given state of health on a cardinal numeric scale, where a value of 1.0 represents full health, 0.0 represents dead, and negative values represent states worse than death. Missing EoT values were imputed using LOCF method.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Patient Perception of Bladder Condition (PPBC) Baseline and Weeks 4, 8, and 12 The PPBC is a validated, global assessment tool using a 6-point Likert scale that asks participants to rate their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. A higher score indicated a worse perception of bladder condition.
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Total Urgency and Frequency Score (TUFS) Baseline and Weeks 4, 8 and 12 The TUFS was calculated by adding the PPIUS scores of every void in a participant's 3-day diary, and dividing this by the number of days recorded in the diary. Due to a programming failure in the e-diary data for the number of pads used was not collected.
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Trial Locations
- Locations (79)
Site US01009
🇺🇸Homewood, Alabama, United States
Site US01005
🇺🇸Huntsville, Alabama, United States
Site US01012
🇺🇸Anchorage, Alaska, United States
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🇺🇸Hawaiian Gardens, California, United States
Site US01081
🇺🇸Los Angeles, California, United States
Site US01021
🇺🇸Murrieta, California, United States
Site US01068
🇺🇸San Diego, California, United States
Site US01064
🇺🇸Valley Village, California, United States
Site US01097
🇺🇸Englewood, Colorado, United States
Site US01026
🇺🇸Pompano Beach, Florida, United States
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