Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder

BMC Urology

Research Article

Linda Cardozo¹  Bimal Malhotra²  Ahmed El-Tahtawy²  Zhonghong Guan²  Vik Khullar³  David Staskin⁴ 

[1] King's College Hospital, SE5 9RS, Denmark Hill, London, UK;Pfizer Inc, 235 East 42nd St, 10017, New York, NY, USA;St. Mary's Hospital, Mint Wing, Norfolk Place, W2 1PG, London, UK;Tufts University School of Medicine, Caritas-St. Elizabeth's Medical Center, 736 Cambridge St, 02135, Boston, MA, USA;

关键词: Overactive Bladder;    Tolterodine;    Urgency Urinary Incontinence;    Exploratory Data Analysis;    Local Research Ethic Committee;   

DOI  :  10.1186/1471-2490-10-14

 received in 2009-11-05, accepted in 2010-08-19,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundFesoterodine 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.MethodsData from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models.ResultsThe 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.ConclusionsA 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.Trial RegistrationThe phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).

【 授权许可】

CC BY   
© Cardozo et al; licensee BioMed Central Ltd. 2010