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).

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 24h (Patient Perception of Intensity of Urgency Scale grade 3 or 4) and eight or more micturitions per 24h 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.

TRIAL REGISTRATION:

Clinical Trials.gov Identifier: NCT00510406.

• Authors: Philip Van Kerrebroeck, François Haab, Javier C Angulo, Viktor Vik, Ferenc Katona, Alberto Garcia-Hernandez, Monique Klaver, Klaudia Traudtner, Matthias Oelke
• Journal: European urology (Eur Urol) Vol. 64 Issue 3 Pg. 398-407 (Sep 2013) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 23537687 (Publication Type: Clinical Trial, Phase II, Controlled Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 European Association of Urology. All rights reserved.

Chemical References

• Adrenergic alpha-1 Receptor Antagonists
• Muscarinic Antagonists
• Quinuclidines
• Sulfonamides
• Tetrahydroisoquinolines
• Urological Agents
• Tamsulosin
• Solifenacin Succinate

Topics

• Adrenergic alpha-1 Receptor Antagonists (administration & dosage, adverse effects)
• Aged
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Dosage Calculations
• Drug Therapy, Combination
• Europe
• Humans
• Lower Urinary Tract Symptoms (diagnosis, drug therapy, physiopathology)
• Male
• Middle Aged
• Muscarinic Antagonists (administration & dosage, adverse effects)
• Quality of Life
• Quinuclidines (administration & dosage, adverse effects)
• Solifenacin Succinate
• Sulfonamides (administration & dosage, adverse effects)
• Tamsulosin
• Tetrahydroisoquinolines (administration & dosage, adverse effects)
• Time Factors
• Treatment Outcome
• Urinary Bladder (drug effects, physiopathology)
• Urination (drug effects)
• Urination Disorders (diagnosis, drug therapy, physiopathology)
• Urodynamics (drug effects)
• Urological Agents (administration & dosage, adverse effects)