Efficacy of solifenacin in patients previously treated with tolterodine extended release 4 mg: results of a 12-week, multicenter, open-label, flexible-dose study.
OBJECTIVE
This study evaluated the use of solifenacin in patients experiencing residual urgency symptoms during treatment with tolterodine extended release (ER) 4 mg for overactive bladder (OAB).


METHODS
This was a 12-week, multicenter, openlabel, flexible-dose study of the efficacy, tolerability, and effects on health-related quality of life (HRQL) of solifenacin in patients aged >or=18 years who had symptoms of OAB for >or=3 months, had been treated with tolterodine ER 4 mg for >or=4 weeks, and wished to switch therapy because of a lack of sufficient subjective improvement in urgency. At baseline (before washout of tolterodine), patients had to have >or=3 urgency episodes/24 hours. After >or=14 days' washout of tolterodine, all patients received oral solifenacin 5 mg/d, with the option of a dose increase to 10 mg at weeks 4 and 8. On 3 consecutive days before the prewashout, postwashout (no drug treatment for OAB), and week 4, 8, and 12 visits (during and at the end of treatment with solifenacin), patients used a bladder diary to document daily symptoms of urgency, urge incontinence, frequency, nocturia, and nocturnal voids. Changes in these measures at study end were compared with prewashout and postwashout values. The Patient Perception of Bladder Condition (PPBC) and Overactive Bladder Questionnaire (OAB-q) were used to assess patient-reported outcomes at prewashout, postwashout, and week 12. Tolerability was evaluated based on the nature, frequency, and severity of observed or reported adverse events (AEs).


RESULTS
Of 606 patients screened, 441 received study medication (mean [SD] age, 61.4 [13.8] years; 88.9% white; 88.2% female). Diary-documented urgency changed from a mean of 6.0 episodes/24 hours at prewashout to 2.6 episodes/24 hours at study end, a mean decrease of 3.4 episodes/24 hours (95% CI, -3.8 to -3.0; P < 0.001). The frequency of all other diary variables was also significantly reduced from prewashout to study end (P < 0.001). The mean PPBC score changed from 4.2 points at prewashout to 3.0 points at study end, a mean improvement of 1.2 points (95% CI, -1.3 to -1.1; P < 0.001). Changes in all OAB-q scales and domains (symptom bother, coping, concern, sleep, social interaction, and total HRQL) from prewashout and postwashout to study end were also statistically significant (P < 0.001). Treatment-emergent AEs were mainly mild or moderate (237/261 [90.8%]) and led to few discontinuations (16/441 [3.6%]). Treatment-emergent AEs included anticholinergic AEs such as dry mouth (77 [17.5%]), constipation (51 [11.6%]), and blurred vision (10 [2.3%]).


CONCLUSIONS
Among these patients with residual urgency after treatment with tolterodine ER 4 mg, solifenacin was associated with significant improvements in urgency and other diary-documented symptoms of OAB. Patients receiving solifenacin also had significant improvements in HRQL and the perceived bother of OAB.
Chancellor
Michael B
MB
Department of Urology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA. michael.chancellor@beaumont.edu
Zinner
Norman
N
Whitmore
Kristene
K
Kobashi
Kathleen
K
Snyder
Jeffrey A
JA
Siami
Paul
P
Karram
Mickey
M
Laramée
Christine
C
Capo'
James P
JP
Seifeldin
Raafat
R
Forero-Schwanhaeuser
Sergio
S
Nandy
Indrani
I
D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D003408:Cresols / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000627:therapeutic use*; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068737:Tolterodine Tartrate; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
D001559:Benzhydryl Compounds; D003408:Cresols; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; D000069464:Solifenacin Succinate