title: Evaluation of an experimental urodynamic platform to identify treatment effects: a randomized, placebo-controlled, crossover study in patients with overactive bladder.
abstract: OBJECTIVE
  To evaluate a urodynamic platform designed to identify treatment effects in small numbers of patients after a short duration of treatment using a medication with known efficacy in overactive bladder (OAB).
  
  
  METHODS
  Twenty women with OAB were randomized in a crossover study with 7-day treatment periods with either tolterodine 4 mg long-acting (LA) or placebo and 7-day washout. Patients underwent urodynamic study (UDS) at baseline, 4-hr post-dose on Day 1 (PD1) and 4 hr post-dose on Day 7 (PD7) in each treatment period. The primary endpoint was the change from baseline in volume at maximum cystometric capacity (MCC) at PD7. As a result of dosing errors, some patients allocated to tolterodine in Period 1 mistakenly received placebo on Day 7. The data from the time points at which patients were dosed incorrectly were excluded from the per protocol (PP) analysis.
  
  
  RESULTS
  The PP and intent to treat (ITT) mean increase in volume at MCC on PD7 for tolterodine compared with placebo was 28.9% (P = 0.038, one-sided) and 23.2% (P = 0.008, one-sided), respectively. The PD7 mean increase in volume at first desire to void was 36.5% (P = 0.054, PP) and 40.3% (P = 0.008, ITT). No volume endpoint at PD1 was statistically significant. Of all the endpoints, MCC was the least variable.
  
  
  CONCLUSIONS
  This crossover design was able to detect a clinically meaningful and statistically significant treatment effect consistent with the previous reports of tolterodine. Despite multiple urodynamics per patient, the study was able to recruit quickly. This model is valuable for evaluating therapeutic effects for existing and novel treatments for OAB.
authors: Merck Research Laboratories, Rahway, New Jersey, USA. tara_frenkl@merck.com
authors: Tara
authors: T
authors: Frenkl
authors: Radha
authors: R
authors: Railkar
authors: Neal
authors: N
authors: Shore
authors: James
authors: J
authors: Bailen
authors: Suzette
authors: S
authors: Sutherland
authors: Joanne
authors: J
authors: Burke
authors: Boyd B
authors: BB
authors: Scott
authors: Marcella
authors: M
authors: Ruddy
authors: Chan
authors: C
authors: Beals
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D003187:Compliance / Q000187:drug effects / Q000502:physiology; D003408:Cresols / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D010665:Phenylpropanolamine / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D015203:Reproducibility of Results; D000068737:Tolterodine Tartrate; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects / Q000502:physiology; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology*
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate