Combination Therapy with Solifenacin and Tamsulosin Oral Controlled Absorption System in a Single Tablet for Lower Urinary Tract Symptoms in Men: Efficacy and Safety Results from the Randomised Controlled NEPTUNE Trial

Abstract Background Storage symptoms are particularly bothersome in men with lower urinary tract symptoms (LUTS) but may not be adequately treated by α-blocker monotherapy. Objective To assess the efficacy and safety of a fixed-dose combination (FDC) of solifenacin and an oral controlled absorption system (OCAS) formulation of tamsulosin compared with placebo and compared with tamsulosin OCAS (TOCAS) monotherapy in men with moderate to severe storage symptoms and voiding symptoms. Design, setting, and participants A double-blind 12-wk phase 3 study in 1334 men with storage and voiding LUTS: total International Prostate Symptom Score (IPSS) ≥13, maximum urinary flow rate (Q max ) 4.0–12.0ml/s, two or more urgency episodes per 24 h of Patient Perception of Intensity of Urgency Scale grade 3 or 4, and eight or more micturitions per 24h. Intervention Patients were randomised to placebo, TOCAS 0.4mg, FDC solifenacin 6mg plus TOCAS 0.4mg, or FDC solifenacin 9mg plus TOCAS 0.4mg. Outcome measurements and statistical analysis Primary efficacy end points were (1) total IPSS and (2) Total Urgency and Frequency Score (TUFS). An FDC met the success criteria if it demonstrated superiority compared with placebo and noninferiority compared with TOCAS for total IPSS, as well as superiority compared with TOCAS for TUFS. Results and limitations Reductions in total IPSS and TUFS were observed with both solifenacin 6mg plus TOCAS (−7.0 and −8.1, respectively) and solifenacin 9mg plus TOCAS (−6.5 and −7.6, respectively) compared with TOCAS (−6.2 and −6.7, respectively) and placebo (−5.4 and −4.4, respectively). Solifenacin 6mg plus TOCAS met all prespecified success criteria for both primary end points, while solifenacin 9mg plus TOCAS met success criteria compared with placebo but not compared with TOCAS. Both FDCs improved quality of life (QoL) measures and were well tolerated, with low incidences of acute urinary retention. Conclusions The FDC of solifenacin 6mg plus TOCAS significantly improved storage and voiding symptoms, as well as QoL parameters, compared with placebo. This FDC also improved storage symptoms and QoL compared with TOCAS alone in men with moderate to severe storage symptoms and voiding symptoms, and it was well tolerated. Trial registration ClinicalTrials.gov Identifier: NCT01018511).