Onset of Efficacy of Tadalafil Once Daily in Men With Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Trial Allen Seftel,*,†, Evan Goldfischer,‡ Edward D. Kim,† Eugene Dula, Haoyue Zeigler† and Patrick Burns† From the Cooper University Medical Center (AS), Camden, New Jersey, Hudson Valley Urology Center (EG), Poughkeepsie, New York, University of Tennessee Graduate School of Medicine (EDK), Knoxville, Tennessee, West Coast Clinical Research (ED), Tarzana, California, and Lilly USA, L. L. C. (HZ, PB), Indianapolis, Indiana Purpose: We evaluated the efficacy onset and safety of tadalafil 2.5 and 5 mg once daily for 14 days compared with placebo in men with erectile dysfunction. Materials and Methods: In this randomized, double-blind, placebo controlled, parallel group study we randomized 372 men after a 4-week run-in period to receive placebo, or tadalafil 2.5 or 5 mg once daily for 14 days, followed by a 14-day open label extension period of tadalafil 5 mg once daily. Primary analysis focused on the cumulative percent of men with a successful intercourse attempt during the first 4 days of treatment. On secondary analysis we evaluated the percent of successful attempts during the study. The Sexual Encounter Profile diary question 3 was used to assess efficacy. Safety was assessed by monitoring adverse events and vital signs. Results: Significantly more men in the tadalafil 5 mg group achieved successful intercourse, as indicated by a yes response to diary question 3, than those on placebo by day 2 (48.6% vs 36.6%, p 0.025). The tadalafil 2.5 mg group did not separate from the placebo group on primary analysis. Secondary analysis showed that men on tadalafil 2.5 mg achieved a significantly higher percent of successful intercourse attempts than those on placebo by day 3 (35.5% vs 27.2%, p 0.025). All groups further improved during the open label extension period. Tadalafil was well tolerated. Conclusions: This prospective trial shows the onset of efficacy of tadalafil 2.5 and 5 mg once daily within a few days of initiating therapy. Key Words: penis, erectile dysfunction, tadalafil, coitus, treatment outcome Abbreviations and Acronyms AE = adverse event ED = erectile dysfunction IIEF-EF = International Index of Erectile Function-Erectile Function PDE5 = phosphodiesterase 5 SEP = Sexual Encounter Profile SEP3 = SEP question 3 TEAE = treatment emergent AE Submitted for publication February 24, 2010. Study received approval from study center ethical review boards. Supported by Lilly USA, L. L. C. * Correspondence: Division of Urology, Coo- per University Medical Center, 3 Cooper Plaza, Suite 411, Camden, New Jersey 08103 (tele- phone: 856-963-3577; FAX: 856-968-8457; e-mail: allendseftel@gmail.com). † Financial interest and/or other relationship with Lilly. ‡ Financial interest and/or other relationship with Lilly, Pfizer, Astellas, GlaxoSmithKline and Ferring. THE efficacy of tadalafil 2.5 and 5 mg once daily as treatment for ED has been shown in clinical trials. 1– 4 To our knowledge the onset of efficacy of tadalafil once daily has not been pro- spectively evaluated to date. Onset of efficacy is an important factor when evaluating PDE5 inhibi- tors. 5 Several groups evaluated the onset of efficacy of PDE5 inhibitors taken as needed in men with ED. 5–7 Specifically for tadalafil, clinical trial results showed that tadalafil 10 and 20 mg received as needed were supe- rior to placebo in effecting an erecto- genic response within 30 minutes of dosing. 6 In previous studies of tadalafil once daily subjects were not instructed on when to attempt intercourse relative to treatment initiation. However, ret- rospective analysis was performed on the onset of efficacy in a subset of men who attempted intercourse on days 1 0022-5347/11/1851-0243/0 Vol. 185, 243-248, January 2011 THE JOURNAL OF UROLOGY ® Printed in U.S.A. © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH,INC. DOI:10.1016/j.juro.2010.09.035 www.jurology.com 243