Targacept, a clinical-stage biopharmaceutical company developing novel neuronal nicotinic receptors (NNR) therapeutics, plans the initiation of a phase IIb clinical study of TC-5214 as a treatment for overactive bladder (OAB). TC-5214 acts potently on alpha3beta4 and other NNRs located in or around the bladder believed to play a key role in bladder contraction and signaling of the urge to urinate.
"Overactive bladder has a devastating effect on quality of life for millions of individuals, and currently available medications have significant drawbacks," said Eric Rovner, M.D., professor of urology, Medical University of S.C., College of Medicine, and an investigator in Targacept's study.
The phase IIb study is a double-blind, placebo-controlled, randomized, parallel-group trial to be conducted at sites in the U.S. The study's co-primary endpoints are change in micturition frequency per 24 hours and change in urinary incontinence episodes per 24 hours, in each case from baseline to 12 weeks. The study, designed to enroll approximately 750 patients, includes a three-to-five-week screening period followed by a 12-week treatment period during which patients receive either one of three doses of TC-5214 (0.5mg, 1mg or 2mg) or placebo twice daily, randomized in a ratio of 2:1:1:1 (placebo, low dose, mid dose, high dose).
Because orally administered TC-5214 is eliminated more than 90% unchanged through the bladder, Targacept believes the compound offers potential for a low dose to be beneficial while minimizing systemic side effects characteristic of current therapies and enhancing patient compliance.
TC-5214 was associated with exaggerated bladder effects in preclinical studies, including increased urinary retention and beneficial changes in bladder contraction, bladder capacity and frequency of urination. TC-5214 already has a substantial safety database resulting from prior clinical studies in approximately 2,400 subjects in a different indication.
"With a strong scientific rationale, supportive findings, measurable clinical endpoints and a well-defined regulatory path, we view overactive bladder as a promising indication for development of this advanced compound," said Dr. Stephen A. Hill, Targacept's president and CEO.