Solifenacin plus tamsulosin combination treatment in men with lower urinary tract symptoms and bladder outlet obstruction: a randomized controlled trial.

BACKGROUND: Alpha blockers are prescribed to manage lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Antimuscarinics are prescribed to treat overactive bladder (OAB). OBJECTIVE: To investigate the safety of a combination of solifenacin (SOLI) and tamsulosin oral controlled absorption system (TOCAS) in men with LUTS and bladder outlet obstruction (BOO). DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, parallel-group, placebo-controlled study in men aged >45 yr with LUTS and BOO for ≥3 mo, total International Prostate Symptom Score (IPSS) ≥8, BOO index ≥20, maximum urinary flow rate (Q(max)) ≤12 ml/s, and voided volume ≥120 ml. INTERVENTIONS: Once-daily coadministration of TOCAS 0.4 mg plus SOLI 6 mg, TOCAS 0.4 mg plus SOLI 9 mg, or placebo for 12 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary (safety) measurements: Q(max) and detrusor pressure at Q(max) (P(det)Q(max)). Other safety assessments included postvoid residual (PVR) volume. Secondary end points included bladder contractile index (BCI) score and percent bladder voiding efficiency (BVE). An analysis of covariance model compared each TOCAS plus SOLI combination with placebo. RESULTS AND LIMITATIONS: Both active treatment groups were noninferior to placebo at end of treatment (EOT) for P(det)Q(max) and Q(max). Mean change from baseline PVR was significantly higher at all time points for TOCAS 0.4 mg plus SOLI 6 mg, and at weeks 2, 12, and EOT for TOCAS 0.4 mg plus SOLI 9 mg versus placebo. Both treatment groups were similar to placebo for BCI and BVE. Urinary retention was seen in only one patient receiving TOCAS 0.4 mg plus SOLI 6 mg. Limitations of the study were that prostate size and prostate-specific antigen level were not measured. CONCLUSIONS: TOCAS 0.4 mg plus SOLI 6 mg or 9 mg was noninferior to placebo at EOT for P(det)Q(max) and Q(max) in men with LUTS and BOO, and there was no clinical or statistical evidence of increased risk of urinary retention.

Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a ß(3)-adrenoceptor agonist, in overactive bladder.

BACKGROUND: Despite several antimuscarinic treatment options for overactive bladder (OAB), there is still a need for distinct treatment approaches to manage this condition. Mirabegron, a ß(3)-adrenoceptor agonist, has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials. OBJECTIVE: To assess the 12-mo safety and efficacy of mirabegron. DESIGN, SETTING, AND PARTICIPANTS: Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo. INTERVENTIONS: After a 2-wk single-blind placebo run-in, patients with eight or more micturitions per 24h and three or more urgency episodes in a 3-d micturition diary were randomized 1:1:1 to once-daily mirabegron 50mg, mirabegron 100mg, or tolterodine extended release (ER) 4 mg for 12 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary variable: incidence and severity of treatment-emergent AEs (TEAEs). Secondary variables: change from baseline at months 1, 3, 6, 9, and 12 in key OAB symptoms. RESULTS AND LIMITATIONS: A total of 812, 820, and 812 patients received mirabegron 50mg, mirabegron 100mg, and tolterodine ER 4 mg, respectively. Baseline demographic and OAB characteristics were similar across groups. TEAEs were reported in 59.7%, 61.3%, and 62.6% of patients, respectively; most were mild or moderate. Serious TEAEs were reported in 5.2%, 6.2%, and 5.4% of patients, respectively. The most common TEAEs were similar across groups. Dry mouth was reported by 2.8%, 2.3%, and 8.6% of patients, respectively. Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2, 0.4, and -0.5mm Hg for mirabegron 50mg, 100mg, and tolterodine ER 4 mg, respectively. Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period. The study was not placebo controlled, which was a limitation. CONCLUSIONS: The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00688688.