Safety and Tolerability of Solifenacin Add-on Therapy
to ?-Blocker Treated Men With Residual Urgency
Steven A. Kaplan,*,† Kurt McCammon,‡ Roger Fincher,§
Allam Fakhoury? and Weizhong He?
From the Weill Medical College of Cornell University, New York, New York (SAK), Eastern Virginia Medical School, Norfolk,
Virginia (KM), Deaconess Medical Building, Spokane, Washington (RF) and Astellas Pharma US Inc.,
Deerfield, Illinois (AF, WH)
Purpose: VICTOR was a 12-week, double-blind, placebo controlled trial assess-
ing the safety and tolerability of solifenacin plus tamsulosin in men with residual
overactive bladder symptoms after tamsulosin monotherapy. Efficacy of solifena-
cin plus tamsulosin vs placebo plus tamsulosin was also evaluated.
Materials and Methods: A total of 398 men 45 years old or older were randomized
to 12 weeks of solifenacin plus tamsulosin or placebo plus tamsulosin once daily. The
study population had 8 or more micturitions per 24 hours and 1 or more urgency
episode per 24 hours after taking tamsulosin for 4 or more weeks, a total Interna-
tional Prostate Symptom Score of 13 or greater, a Patient Perception of Bladder
Condition score of 3 or greater, a post-void residual of 200 ml or less and a peak flow
rate of 5 ml per second or greater. Adverse events were monitored throughout the
study. The primary efficacy end point was mean change from baseline to week 12 in
micturitions per 24 hours. Secondary measures included mean change in urgency
episodes per 24 hours, and changes in Patient Perception of Bladder Condition,
Urgency Perception Scale and total International Prostate Symptom Scores.
Results: The most frequent adverse events in the solifenacin plus tamsulosin
and placebo plus tamsulosin groups were dry mouth (7% and 3%, respectively)
and dizziness (3% and 2%, respectively). Of the patients on solifenacin plus
tamsulosin 7 (3%) reported retention and 3 required catheterization. No patients
on placebo plus tamsulosin reported retention. Patients on solifenacin plus tam-
sulosin vs placebo plus tamsulosin showed larger reductions in frequency but not
of statistical significance (?1.05 vs ?0.67, p ? 0.135). However, patients on
solifenacin plus tamsulosin vs placebo plus tamsulosin did show statistically
significant reductions in urgency (?2.18 vs ?1.10, p ?0.001). Patient reported
outcome measures showed no significant between group differences.
Conclusions: Solifenacin plus tamsulosin was well tolerated. There was a low
incidence of urinary retention requiring catheterization. At week 12 solifenacin
plus tamsulosin decreased daily micturitions and urgency episodes. Only urgency
reached statistical significance vs placebo plus tamsulosin.
Key Words: urinary bladder, overactive; muscarinic antagonists;
TRADITIONALLY, male LUTS are attrib-
uted to BPH/BOO while female LUTS
are attributed to OAB/detrusor overac-
include slow stream, splitting/spraying,
intermittency, terminal dribbling and
AE ? adverse event
BOO ? bladder outlet obstruction
BPH ? benign prostatic
EOT ? end of treatment
I-PSS ? International Prostate
LUTS ? lower urinary tract
OAB ? overactive bladder
PBO ? placebo
PPBC ? Patient Perception of
PVR ? post-void residual
SOL ? solifenacin
TAM ? tamsulosin
TEAE ? treatment emergent
TIMES ? Tolterodine and
Tamsulosin in Men with LUTS
Including OAB: Evaluation of
Efficacy and Safety
UPS ? Urgency Perception Scale
VICTOR ? VESIcare® In
Combination With Tamsulosin in
OAB Residual Symptoms
Submitted for publication February 10, 2009.
* Correspondence: Weill Medical College of Cor-
nell University, NewYork-Presbyterian Hospital/Weill
Cornell Medical Center, 425 East 61st St., New York,
New York 10065-4805 (telephone: 212-746-4811; FAX:
212-746-0780; e-mail: email@example.com).
† Financial interest and/or other relationship with
Astellas, Watson, Neotract, National Institutes of
Health, National Institute of Diabetes and Digestive
and Kidney Diseases, Sanofi-Synthelabo and Pfizer.
‡ Financial interest and/or other relationship
with AMS, Astellas, and Engineers and Doctors.
§ Nothing to disclose.
? Financial interest and/or other relationship
Editor’s Note: This article is the
fifth of 5 published in this issue
for which category 1 CME credits
can be earned. Instructions for
obtaining credits are given with
the questions on pages 2988 and
THE JOURNAL OF UROLOGY®
Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 182, 2825-2830, December 2009
Printed in U.S.A.
and OAB because they perceive themselves to have
prostate rather than bladder problems.
The sample size calculation indicated that 161
subjects per arm provided 80% or more power (2-
sided ? ? 0.05) to detect a difference of –0.94 mic-
turitions per 24 hours using a SD of 3.0. It is not
known whether the methodology presumed for pa-
tients treated for OAB can be readily applied to
those with BPH with residual OAB symptoms al-
ready being treated with an ?-blocker for 4 or more
weeks. Therefore, a possible limitation of VICTOR is
that the estimated difference between PBO plus
TAM and SOL plus TAM was not known. We used
the estimated difference between PBO and SOL
from a pooled analysis of the SOL pivotal studies to
Further studies of combination therapy with SOL
plus TAM should include larger patient populations
and longer durations of therapy. Although antimus-
carinics appear to be well tolerated in men with
BOO, data from men with varying degrees of BOO
are needed to identify subgroups within the general
male LUTS population. The tools used to measure
symptoms and bother may need to be reevaluated
and validated in more appropriate patient popula-
tions. In men with severe BOO antimuscarinic ther-
apy may require closer supervision. Urodynamics
might help identify patients who would benefit most
from combination therapy. The International Con-
sultation on Incontinence recommends pressure flow
urodynamics in the evaluation of men when a pre-
cise diagnosis of BOO is important.22To our knowl-
edge this is the only method that can differentiate
men with a low peak flow rate due to detrusor un-
deractivity from those with BOO.
Overall SOL plus TAM was well tolerated compared
to PBO plus TAM. The primary objective of the
study, to study the safety and tolerability of SOL
plus TAM in men with residual OAB symptoms after
TAM monotherapy, was met. There was a low inci-
dence of retention requiring catheterization. Thus,
while ?-blockers may adequately manage voiding
LUTS in men, residual, bothersome, storage LUTS
may be improved with the addition of SOL.
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SOLIFENACIN PLUS TAMSULOSIN FOR RESIDUAL URGENCY AND FREQUENCY