Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder.
BACKGROUND
Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine.


METHODS
Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models.


RESULTS
The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively.


CONCLUSIONS
A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials.


BACKGROUND
The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).
Cardozo
Linda
L
King's College Hospital, Denmark Hill, London SE5 9RS, UK. lcardozo@compuserve.com
Khullar
Vik
V
El-Tahtawy
Ahmed
A
Guan
Zhonghong
Z
Malhotra
Bimal
B
Staskin
David
D
D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology / Q000652:urine
D001559:Benzhydryl Compounds; D018727:Muscarinic Antagonists; C526675:fesoterodine