Randomized, double-blind, placebo- and propiverine-controlled trial of the once-daily antimuscarinic agent solifenacin in Japanese patients with overactive bladder.
OBJECTIVE
To compare solifenacin succinate (5 and 10 mg once-daily) to placebo and propiverine hydrochloride (20 mg once-daily), respectively, in Japanese patients with overactive bladder syndrome (OAB).


METHODS
A multicentre, 12-week, double-blind phase III trial randomized men and women aged > or = 20 years with OAB to solifenacin 5 or 10 mg, propiverine 20 mg, or placebo. Changes at endpoint in number of voids/24 h, urgency, incontinence, urgency incontinence and nocturia episodes, volume voided/void, restoration of continence and quality of life (QoL) were examined.


RESULTS
Of 1593 patients randomized, 1584 were treated; at the endpoint there were greater reductions in mean (sd) voids/24 h with solifenacin 5 mg, at -1.93 (1.97), and 10 mg, at -2.19 (2.09), and propiverine 20 mg, at -1.87 (2.70), than with placebo, at -0.94 (2.29) (P < 0.001 for all). Solifenacin (5 and 10 mg) was superior to placebo, and no worse than propiverine 20 mg, for this variable. There were significantly fewer mean (sd) urgency, incontinence and urgency incontinence episodes with solifenacin and propiverine than with placebo, with respective changes on placebo of - 1.28 (2.90), - 0.72 (1.95) and - 0.69 (2.00); solifenacin 5 mg, - 2.41 (2.88), -1.59 (2.12) and -1.45 (1.89) (P < 0.001 for all), and 10 mg, -2.78 (2.82), - 1.60 (1.81) and - 1.52 (1.77) (P < 0.001 for all), and propiverine 20 mg, -2.30 (3.08), -1.25 (2.79) and - 1.19 (2.20) (P < 0.001, = 0.002 and = 0.002 respectively). All active treatments vs placebo improved the volume voided (P < 0.001 for all) and QoL; solifenacin 10 mg reduced nocturia episodes (P = 0.021) and significantly improved urgency episodes (P = 0.012) and volume voided (P = 0.009) vs propiverine 20 mg, and solifenacin 5 mg caused less dry mouth (P = 0.003). Solifenacin 10 mg caused more dry mouth (P = 0.012) and occurrences of constipation (P = 0.004) than propiverine 20 mg, but discontinuation rates between both treatment groups were similar. Continence was restored at endpoint in more than half of the patients on active treatment.


CONCLUSIONS
Solifenacin 5 and 10 mg once daily significantly improved the symptoms of OAB compared with placebo. Solifenacin therapy at 5 mg once daily is well-tolerated; 10 mg can be given if additional efficacy is required.
Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan. yamaosa@cc.fmu.ac.jp
Osamu
O
Yamaguchi
Eiji
E
Marui
Hidehiro
H
Kakizaki
Naoki
N
Itoh
Takashi
T
Yokota
Hiroshi
H
Okada
Osamu
O
Ishizuka
Seiichiro
S
Ozono
Momokazu
M
Gotoh
Takahide
T
Sugiyama
Narihito
N
Seki
Masaki
M
Yoshida
D000328:Adult; D000368:Aged; D001561:Benzilates / Q000009:adverse effects / Q000627:therapeutic use*; D003248:Constipation / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D011812:Quinuclidines / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D014563:Urodynamics / Q000502:physiology*; D014987:Xerostomia / Q000139:chemically induced
D001561:Benzilates; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; C015586:propiverine; D000069464:Solifenacin Succinate