Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo‐ and tolterodine‐controlled phase 2 dose‐finding study

Abstract

Early results using two new agents to treat urinary incontinence are published. The use of Ro 115–1240 in women with stress urinary incontinence is presented, with encouraging results. This will lead to further studies in more patients. Solifenacin was evaluated in a dose‐finding study and the results presented here; the results of the phase III study appear next month. OBJECTIVES To evaluate the dose‐response relationship and safety/tolerability of solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and to compare its efficacy and safety/tolerability with tolterodine 2 mg twice daily. PATIENTS AND METHODS This multicentre study included a 2‐week single‐blind placebo run‐in, a 4‐week double‐blind placebo‐controlled active treatment phase, and a 2‐week follow‐up. Men and women with an OAB and urodynamic evidence of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or 20 mg once daily, or tolterodine 2 mg twice daily. RESULTS Of 265 patients enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and 20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs placebo, whereas tolterodine did not; the mean change with tolterodine was between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean change from baseline to endpoint in mean volume voided/void. For incontinence and urgency episodes/24 h the solifenacin dose groups showed numerically superior changes vs placebo; the mean effects with tolterodine were generally smaller than with solifenacin. Most of the efficacy effect of solifenacin was evident at 2 weeks. Quality‐of‐life outcomes supported the efficacy results. Solifenacin 5 and 10 mg were well tolerated; there were no serious treatment‐related adverse events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for placebo and 24% for tolterodine. CONCLUSION In this study, the 5‐ and 10‐mg doses of solifenacin appeared to be the most clinically effective for treating OAB, considering the balance between efficacy, quality of life and tolerability. From the results of this study solifenacin 5 and 10 mg were selected for further evaluation in large‐scale phase 3 studies.