A Phase 4, Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Men With Overactive Bladder (OAB) Symptoms While Taking the Alpha Blocker Tamsulosin Hydrochloride for Lower Urinary Tract Symptoms (LUTS) Due to Benign Prostatic Hyperplasia (BPH)
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 715
- Locations
- 79
- Primary Endpoint
- Change From Baseline to End of Treatment (EoT) in Mean Number of Micturitions Per Day
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Mirabegron (Drug)
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.
Intervention: Tamsulosin Hydrochloride (Drug)
Placebo
Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.
Intervention: Placebo (Drug)
Placebo
Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.
Intervention: Tamsulosin Hydrochloride (Drug)
Outcomes
Primary Outcomes
Change From Baseline to End of Treatment (EoT) in Mean Number of Micturitions Per Day
Time Frame: 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 Outcomes
- 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)
- 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)
- Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Coping Score(Baseline and Weeks 4, 8, and 12)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Change From Baseline to Week 4, Week 8, Week 12 and EoT in Symptom Bother Score(Baseline and Weeks 4, 8, and 12)
- 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)
- 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)
- Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Concern Score(Baseline and Weeks 4, 8, and 12)
- Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Voiding Score(Baseline and Weeks 4, 8, and 12)
- Change From Baseline to Week 4, Week 8, Week 12, and EoT in IPSS Subscale Storage Score(Baseline and Weeks 4, 8, and 12)
- 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)
- Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Sleep Score(Baseline and Weeks 4, 8 and 12)
- 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)
- 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)
- 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)