Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil

Abstract

Objective:

Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy.

Research design and methods:

In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function – Erectile Function (IIEF-EF) domain scores <26 following lead-in treatment completed a 4 week washout period, then randomized to TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. Main outcome measures obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy.

Clinical trial registration:

NCT01130532.

Main outcome measures:

International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2–5.

Results:

Endpoint data was obtained from 590 men (391 TAD; 199 PBO). Results for all IIEF and SEP measures were significantly better for TAD-OaD (p < 0.001 for all) compared to PBO and were comparable to those observed during PRN-PDE5I treatment. TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated.

Conclusion:

Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

Keywords: :

• As-needed dosing
• Erectile dysfunction
• Once daily dosing
• Sildenafil
• Tadalafil
• Vardenafil

Transparency

Declaration of funding

The conduct of the study, the completion of the post hoc analyses, and the preparation of this manuscript were fully funded by Eli Lilly and Company (Lilly).

Declaration of financial/other relationships

E.K. has disclosed that he is a speaker for Watson, Astellas, Lilly, and Auxilium, and serves as an investigator and advisor for Lilly. A.S. has disclosed that he is a consultant for Lilly, Endo, Abbot, Actient, and Auxilium, and an investigator for Lilly and Auxilium; he also serves on the editorial board for the Journal of Urology. E.G. has disclosed that he is a speaker/consultant for Astellas, Lilly, Ferring, Janssen, and Watson; he is also a clinical trial investigator for Astellas, Allergan, and Janssen. S.B. and P.B. have disclosed that they are full time employees at and minor stockholders in Eli Lilly and Company.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

We would like to thank Scott Burke and Cindi Wood (inVentiv Health Clinical) for their technical expertise in helping to develop, prepare, and complete this manuscript.