Fesoterodine: Individualised Treatment of Urgency Urinary Incontinence Across Patient Groups  Jean-Jacques Wyndaele  European Urology Supplements  Volume 10, Issue 1, Pages 14-22 (March 2011) DOI: 10.1016/j.eursup.2011.01.003 Copyright © 2011 Terms and Conditions

Fig. 1 Esterase-mediated versus CYP2D6-mediated formation of 5-hydroxymethyl tolterodine. Reproduced with permission from Bentham Science Publishers Ltd Copyright 2010, from Malhotra B, Gandelman K, Sachse R, Wood N, Michel MC. The design and development of fesoterodine as a prodrug of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of tolterodine. Curr Med Chem 2009;16:4481–9 [15]. Tolt=tolterodine; 5-HMT=5-hydroxymethyl tolterodine. European Urology Supplements 2011 10, 14-22DOI: (10.1016/j.eursup.2011.01.003) Copyright © 2011 Terms and Conditions

Fig. 2 Change from baseline to week 12 in urgency urinary incontinence episodes per 24h for fesoterodine 8mg versus tolterodine ER 4mg and placebo. Copyright 2010 Wiley. Used with permission from Herschorn S, Swift S, Guan Z, Carlsson M, Morrow JD, Brodsky M, Gong J. Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trial. BJU Int, John Wiley and Sons [20]. European Urology Supplements 2011 10, 14-22DOI: (10.1016/j.eursup.2011.01.003) Copyright © 2011 Terms and Conditions

Fig. 3 Baseline to week 12 changes in Overactive Bladder Questionnaire scores. Data represent the full-analysis set (placebo, 313; tolterodine ER, 641; fesoterodine, 636). Used with permission from Herschorn S, Swift S, Guan Z, Carlsson M, Morrow JD, Brodsky M, Gong J. Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trial. BJU Int, John Wiley and Sons [20]. European Urology Supplements 2011 10, 14-22DOI: (10.1016/j.eursup.2011.01.003) Copyright © 2011 Terms and Conditions

Fig. 4 Change from baseline to weeks 1, 4, and 12 in urgency urinary incontinence episodes per 24h. Data represent the full analysis set for subjects reporting symptoms at baseline. Subjects in the fesoterodine group received fesoterodine 4mg for the first week and then fesoterodine 8mg for the remaining 11 weeks. Copyright 2010 Wiley. Used with permission from Kaplan SA, Schneider T, Foote JE, Guan Z, Carlsson M, Gong J. Superior efficacy of fesoterodine over tolterodine extended release with rapid onset: a prospective, head-to-head, placebo-controlled trial. BJU Int, John Wiley and Sons [19]. BL=baseline; ER=extended release; UUI=urgency urinary incontinence. *p<0.05 tolterodine ER versus placebo. †p<0.05 fesoterodine versus placebo. ‡p=0.05 fesoterodine versus tolterodine ER. European Urology Supplements 2011 10, 14-22DOI: (10.1016/j.eursup.2011.01.003) Copyright © 2011 Terms and Conditions

Fig. 5 Three-day diary-dry rates at weeks 1, 4, and 12. Data represent the full analysis set for subjects reporting symptoms at baseline. Subjects in the fesoterodine group received fesoterodine 4mg for the first week and then fesoterodine 8mg for the remaining 11 weeks. Copyright 2010 Wiley. Used with permission from Kaplan SA, Schneider T, Foote JE, Guan Z, Carlsson M, Gong J. Superior efficacy of fesoterodine over tolterodine extended release with rapid onset: a prospective, head-to-head, placebo-controlled trial. BJU Int, John Wiley and Sons [19]. ER=extended release. *p<0.05 tolterodine ER versus placebo. †p<0.05 fesoterodine versus placebo. ‡p=0.05 fesoterodine versus tolterodine ER. European Urology Supplements 2011 10, 14-22DOI: (10.1016/j.eursup.2011.01.003) Copyright © 2011 Terms and Conditions

Fig. 6 Change from baseline to weeks 1, 4, and 12 in mean voided volume per micturition, total micturitions per 24h, nocturnal micturitions per 24h, urgency episodes per 24h, severe urgency episodes per 24h, and frequency-urgency sum per 24h. Error bars represent the standard error of the mean. Data represent the full analysis set for subjects reporting symptoms at baseline. Subjects in the fesoterodine group received fesoterodine 4mg for the first week and then fesoterodine 8mg for the remaining 11 weeks. Copyright 2010 Wiley. Used with permission from Kaplan SA, Schneider T, Foote JE, Guan Z, Carlsson M, Gong J. Superior efficacy of fesoterodine over tolterodine extended release with rapid onset: a prospective, head-to-head, placebo-controlled trial. BJU Int, John Wiley and Sons [19]. BL=baseline; ER=extended release; MVV=mean voided volume; UUI=urgency urinary incontinence. *p<0.05 tolterodine ER versus placebo. †p<0.05 fesoterodine versus placebo. ‡p=0.05 fesoterodine versus tolterodine ER. European Urology Supplements 2011 10, 14-22DOI: (10.1016/j.eursup.2011.01.003) Copyright © 2011 Terms and Conditions

Fig. 7 Least squares mean change from baseline to end of treatment in number of urgency urinary incontinence (UUI) episodes per 24h stratified by number of baseline UUI episodes. Copyright 2010 Wiley. Used with permission from Cardozo L, Khullar V, Wang JT, Guan Z, Sand PK. Fesoterodine in patients with overactive bladder syndrome: can the severity of baseline urgency urinary incontinence predict dosing requirement? BJU Int, John Wiley and Sons [26]. European Urology Supplements 2011 10, 14-22DOI: (10.1016/j.eursup.2011.01.003) Copyright © 2011 Terms and Conditions

Fig. 8 Overactive Bladder Questionnaire scores for total health-related quality of life (HRQoL), the four HRQoL domains, and symptom bother are shown at baseline and after 12 weeks of fesoterodine treatment. Copyright 2010 Wiley. Used with permission from Wyndaele JJ, Goldfischer ER, Morrow JD, Gong J, Tseng LJ, Guan Z, Choo MS. Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study. Int J Clin Pract, John Wiley and Sons [30]. European Urology Supplements 2011 10, 14-22DOI: (10.1016/j.eursup.2011.01.003) Copyright © 2011 Terms and Conditions