ORIGINAL RESEARCH—ED PHARMACOTHERAPY
Efficacy of Tadalafil in Men with Erectile Dysfunction Naïve to Phosphodiesterase 5 Inhibitor Therapy Compared with Prior Responders to Sildenafil Citrate

https://doi.org/10.1111/j.1743-6109.2006.00273.xGet rights and content

ABSTRACT

Introduction

Tadalafil, an inhibitor of phosphodiesterase 5 (PDE5), is indicated for treatment of erectile dysfunction. Most tadalafil clinical trials excluded patients with unsuccessful prior treatment with sildenafil citrate (sildenafil).

Aim

This retrospective analysis of pooled data from 14 tadalafil clinical trials examines the effect of this exclusion by comparing efficacy results in 1,349 patients without prior sildenafil use (naïve, presumably a mixture of potential responders and nonresponders) with efficacy results in 1,440 patients previously responsive to sildenafil (prior responders).

Main Outcome Measures

Efficacy measures included the International Index of Erectile Function (IIEF) erectile function (EF) domain, overall satisfaction (OS), and intercourse satisfaction (IS) domain scores; Sexual Encounter Profile (SEP) diary questions 2 through 5 (SEP2 [successful penetration], SEP3 [successful intercourse], SEP4 (satisfaction with hardness of erection), and SEP5 [overall satisfaction with the sexual experience]); and a Global Assessment Question (GAQ1) (13/14 trials) about erection improvement. Efficacy was compared using analysis of covariance (IIEF and SEP) and logistic regression (GAQ1) models.

Methods

After a 4‐week, treatment‐free, run‐in period, patients in 14 double‐blind, placebo‐controlled, parallel‐group trials were treated with tadalafil 10 mg, tadalafil 20 mg, or placebo for 12 weeks (dosed as needed before sexual activity, no more than once daily).

Results

Tadalafil improved erectile function compared with placebo (P < 0.001) in naïve patients and sildenafil prior responders for all efficacy measures. For most efficacy outcomes, responses in the naïve group (probable mix of responders and nonresponders) were not statistically different from responses in the prior‐responder group (P ≥ 0.10).

Conclusions

The similar responses of these two patient groups observed in this post hoc analysis suggest, but do not confirm, that exclusion of sildenafil nonresponders in previously reported tadalafil clinical trials may not have substantially affected efficacy outcomes. Tadalafil improved erectile function in patients naïve to PDE5 inhibitor therapy and in patients who previously responded to sildenafil therapy. Broderick GA, Donatucci CF, Hatzichristou D, Torres LO, Valiquette L, Zhao Y, Loughney K, Sides GD, and Ahuja S. Efficacy of tadalafil in men with erectile dysfunction naïve to phosphodiesterase 5 inhibitor therapy compared with prior responders to sildenafil citrate. J Sex Med 2006;3:668–675.

Introduction

Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor used for the treatment of erectile dysfunction (ED), defined as the persistent inability to achieve or maintain an erection sufficient for sexual activity [1]. In clinical trials, tadalafil improved erectile function in a broad population with mild to severe ED, as well as in various subpopulations (e.g., men with ED and diabetes mellitus) [2, 3, 4, 5, 6]. In these trials, nonresponders to prior sildenafil treatment, as identified by the investigators, were often excluded. This raised the possibility that the efficacy of tadalafil may have been elevated in the trials due to this exclusion, as the sildenafil nonresponders may also have been less likely to respond to tadalafil. This retrospective analysis explored this possibility by comparing the efficacy of tadalafil in patients with no history of PDE5 inhibitor therapy (naïve patients, presumably a mixture of potential responders and potential nonresponders) with that in patients who had responded to prior sildenafil treatment (prior responders).

Section snippets

Methods

In this retrospective analysis of pooled data from 14 double‐blind, placebo‐controlled, parallel‐group trials in the general ED population, the efficacy of tadalafil in 1,349 naïve patients was compared with that in 1,440 sildenafil prior responders. The trials were conducted worldwide at 184 sites in 23 countries between September 2000 and December 2003 (Table 1). The details of the general study design, efficacy, and safety measures were described in previous pooled data analyses of tadalafil

Study Population

Demographic and baseline characteristics were summarized for the naïve and prior‐responder groups, but no statistical comparisons were performed (Table 2). The percentage of patients with ED ≥1‐year duration ranged from 80% to 88% in the naïve‐patient groups treated with placebo, tadalafil 10 mg, and tadalafil 20 mg, and ranged from 92% to 96% in the prior‐responder groups. The percentage of patients with baseline IIEF‐EF scores that indicated severe ED ranged from 28% to 29% in the

Discussion

Tadalafil 10 mg and 20 mg significantly improved erectile function compared with placebo in both naïve and prior‐responder patients for all efficacy measures tested. For most of these efficacy measures, the responses of the naïve and prior‐responder patients were statistically similar. Thus, the results of this retrospective pooled data analysis suggest that the efficacy outcomes in clinical trials of tadalafil were not affected substantially by the exclusion of sildenafil nonresponders.

Conflict of Interest

Drs. Zhao, Sides, and Ahuja are employees of Eli Lilly and Co. Dr. Loughney is an employee of ICOS Corporation.

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