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.
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.


METHODS
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 (Qmax) 4.0-12.0 ml/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.


METHODS
Patients were randomised to placebo, TOCAS 0.4 mg, FDC solifenacin 6 mg plus TOCAS 0.4 mg, or FDC solifenacin 9 mg plus TOCAS 0.4 mg.


METHODS
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.


CONCLUSIONS
Reductions in total IPSS and TUFS were observed with both solifenacin 6 mg plus TOCAS (-7.0 and -8.1, respectively) and solifenacin 9 mg 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 6 mg plus TOCAS met all prespecified success criteria for both primary end points, while solifenacin 9 mg 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 6 mg 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.
Maastricht University Medical Center, Maastricht, The Netherlands.
Philip
P
van Kerrebroeck
Christopher
C
Chapple
Ted
T
Drogendijk
Monique
M
Klaver
Roman
R
Sokol
Mark
M
Speakman
Klaudia
K
Traudtner
Marcus J
MJ
Drake
D000042:Absorption; D000284:Administration, Oral; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000368:Aged; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy*; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000069464:Solifenacin Succinate; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013607:Tablets; D000077409:Tamsulosin; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D058668:Adrenergic alpha-1 Receptor Antagonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D013449:Sulfonamides; D013607:Tablets; D044005:Tetrahydroisoquinolines; D000077409:Tamsulosin; D000069464:Solifenacin Succinate
Lower urinary tract symptoms; Solifenacin; Storage symptoms; Tamsulosin OCAS; Voiding symptoms