This trial was registered with ClinicalTrials.gov NCT-00768521.
Original Clinical Article
Version of Record online: 8 SEP 2011
Copyright © 2011 Wiley Periodicals, Inc.
Neurourology and Urodynamics
Volume 31, Issue 1, pages 69–74, January 2012
How to Cite
Frenkl, T., Railkar, R., Shore, N., Bailen, J., Sutherland, S., Burke, J., Scott, B. B., Ruddy, M. and Beals, C. (2012), Evaluation of an experimental urodynamic platform to identify treatment effects: A randomized, placebo-controlled, crossover study in patients with overactive bladder. Neurourol. Urodyn., 31: 69–74. doi: 10.1002/nau.21094
Conflicts of interest: All authors with the exception of Neal Shore, James Bailen, and Suzette Sutherland are employed by Merck & Co., Inc. and may own stock options in the company.
- Issue online: 23 JAN 2012
- Version of Record online: 8 SEP 2011
- Manuscript Accepted: 8 FEB 2011
- Manuscript Received: 29 SEP 2010
- overactive bladder;
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).
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.
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.
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. Neurourol. Urodynam. 31:69–74, 2012. © 2011 Wiley Periodicals, Inc.