Efficacy and Safety of Solifenacin Plus Tamsulosin OCAS in Men with Voiding and Storage Lower Urinary Tract Symptoms: Results from a Phase 2, Dose-finding Study (SATURN)
1. Maastricht University Medical Centre, Maastricht, The Netherlands;2. Hôpital Tenon, Paris, France;3. Hospital Universitario de Getafe, Madrid, Spain;4. Thomayer Hospital, Prague, Czech Republic;5. Josa Andras Hospital, Nyiregyhaza, Hungary;6. Astellas Pharma Europe B.V., Leiden, The Netherlands;g Hannover Medical School, Hannover, Germany
Abstract:
Background
Storage symptoms are often undertreated in men with lower urinary tract symptoms (LUTS).
Objective
To evaluate the combination of an antimuscarinic (solifenacin) with an α-blocker (tamsulosin) versus tamsulosin alone in the treatment of men with LUTS.
Design, setting, and participants
A double-blind, 12-wk, phase 2 study in 937 men with LUTS (≥3 mo, total International Prostate Symptom Score [IPSS] ≥13, and maximum urinary flow rate 4.0–15.0 ml/s).
Intervention
Eight treatment groups: tamsulosin oral controlled absorption system (OCAS) 0.4 mg; solifenacin 3, 6, or 9 mg; solifenacin 3, 6 or 9 mg plus tamsulosin OCAS 0.4 mg; or placebo.
Outcome measurements and statistical analysis
The primary efficacy end point was change from baseline in total IPSS. Secondary end points included micturition diary and quality-of-life (QoL) parameters. Post hoc subgroup analyses were performed by severity of baseline storage symptoms, with statistical comparisons presented only for tamsulosin OCAS alone versus combination therapy, due to the small sample size of the solifenacin monotherapy and placebo subgroups.
Results and limitations
Combination therapy was associated with significant improvements in micturition frequency and voided volume versus tamsulosin OCAS alone in the total study population; improvements in total IPSS were not significant. Statistically significant improvements in urgency episodes, micturition frequency, total urgency score, voided volume, IPSS storage subscore, IPSS-QoL index, and Patient Perception of Bladder Condition were observed in a subpopulation of men with two or more urgency episodes per 24 h (Patient Perception of Intensity of Urgency Scale grade 3 or 4) and eight or more micturitions per 24 h at baseline (storage symptoms subgroup) with combination therapy versus tamsulosin OCAS alone (p ≤ 0.05 for the dose–response slope, all variables). Combination therapy was well tolerated, and adverse events were consistent with the safety profiles of both compounds.
Conclusions
Solifenacin plus tamsulosin OCAS did not significantly improve IPSS in the total study population but offered significant efficacy and QoL benefits over tamsulosin OCAS monotherapy in men with both voiding and storage symptoms at baseline. Combination therapy was well tolerated.
