title: Effects of voluntary dose escalation in a placebo-controlled, flexible-dose trial of fesoterodine in subjects with overactive bladder.
abstract: OBJECTIVE
  To characterize the response to fesoterodine treatment for overactive bladder (OAB) in subjects who did or did not choose to dose escalate in a flexible-dose study.
  
  
  METHODS
  Subjects were randomized to fesoterodine 4  mg or placebo. At week 2, subjects could remain on 4  mg (non-escalators) or choose to increase to 8  mg (escalators) for the remaining 10 weeks (sham escalation for placebo). Subjects completed 3-day bladder diaries at baseline, week 2 and week 12 noting micturitions, urgency episodes, and urgency urinary incontinence (UUI) episodes.
  
  
  RESULTS
  Sixty-three per cent of 438 subjects randomized to fesoterodine and 73% of 445 randomized to placebo dose escalated. At baseline, fesoterodine escalators had significantly more micturitions and urgency episodes than fesoterodine non-escalators (P < 0.001); at week 2, before dose escalation, diary-dry rate and improvement in micturitions and urgency episodes were significantly greater among fesoterodine non-escalators versus escalators (P < 0.001); and by week 12, after dose escalation, diary-dry rate and improvements in micturitions and UUI episodes were similar between fesoterodine non-escalators and escalators (P > 0.05). The placebo escalator group did not demonstrate a similar response over placebo non-escalators following the dose escalation decision point.
  
  
  CONCLUSIONS
  A rapid and robust response to fesoterodine 4  mg was demonstrated in non-escalators. Subjects who chose to dose escalate to fesoterodine 8  mg at week 2 showed significant improvement by week 12 versus baseline and week 2 (prior to escalation), as well as versus placebo. Dose escalation to 8  mg fesoterodine provided subjects with efficacy and tolerability similar to those who were satisfied with the 4-mg dose.
authors.affiliation: St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA. dstaskin@gmail.com
authors.forename: David
authors.initials: D
authors.lastname: Staskin
authors.forename: Vik
authors.initials: V
authors.lastname: Khullar
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
authors.forename: Jon D
authors.initials: JD
authors.lastname: Morrow
authors.forename: Franklin
authors.initials: F
authors.lastname: Sun
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Guan
authors.forename: Roger
authors.initials: R
authors.lastname: Dmochowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D013997:Time Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D014549:Urinary Incontinence / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D018727:Muscarinic Antagonists; D010919:Placebos; C526675:fesoterodine