Elsevier

European Urology

Volume 65, Issue 2, February 2014, Pages 455-464
European Urology

Platinum Priority – Sexual Medicine
Editorial by Paolo Verze, Davide Arcaniolo, Roberto La Rocca and Vincenzo Mirone on pp. 465–466 of this issue
Tadalafil Once Daily in Men with Erectile Dysfunction: An Integrated Analysis of Data Obtained from 1913 Patients from Six Randomized, Double-blind, Placebo-controlled, Clinical Studies

https://doi.org/10.1016/j.eururo.2013.09.037Get rights and content

Abstract

Background

This analysis explores tadalafil once-daily treatment for 12 wk in clinical subpopulations of men with erectile dysfunction (ED).

Objective

Assess the efficacy and safety of once-daily tadalafil 2.5 mg and 5 mg in patients with different ED characteristics and comorbidities.

Design, setting, and participants

This analysis integrated data from six randomized, double-blind, placebo-controlled studies that assigned 1913 men with ≥3-mo history of ED either to once-daily placebo (n = 596), tadalafil 2.5 mg (n = 394), or tadalafil 5 mg (n = 923). Clinical factors examined included: ethnicity, age, obesity, alcohol consumption, smoking, comorbidities, concomitant medication, and ED characteristics (etiology, duration, severity).

Outcome measurements and statistical analysis

Descriptive statistics were reported for efficacy and safety, including International Index of Erectile Function Erectile Function Domain (IIEF-EF) scores and Sexual Encounter Profile question 3 (SEP3) responses. Clinical factors were included in analysis of covariance models using last observation carried forward for SEP3 and IIEF-EF scores.

Results and limitations

Both tadalafil doses significantly improved SEP3 responses (least-squares [LS] mean change: 17.8% and 23.6%, respectively) and IIEF-EF scores (LS mean change: 4.2; 5.4) compared with placebo (p < 0.01). Treatment with 2.5 mg and 5 mg tadalafil resulted in IIEF-EF LS mean improvements ≥4 (minimal clinically important difference [MCID]) in patients with hypertension (4.3 [95% confidence interval (CI), 2.9–5.7]; 4.7 [95% CI, 3.5–5.8]), cardiac disorder (7.0 [95% CI, 4.7–9.3]; 6.3 [95% CI, 4.4–8.2]), or hyperlipidemia (5.3 [95% CI, 3.4–7.1]; 5.8 [95% CI, 4.3–7.4]). Obese patients (4.7 [95% CI, 3.4–6.0]), smokers (4.8 [95% CI, 3.0–6.7]), and psychogenic ED (7.3 [95% CI, 5.0–9.6]) reached MCID only after treatment with 5 mg tadalafil. Severity-specific MCID (IIEF-EF change ≥7) was achieved by 44.5% of patients with severe baseline ED treated with tadalafil 5 mg, compared with 11.6% of placebo-treated patients. No unexpected safety findings were observed. These analyses were performed on integrated data and can only provide descriptive results to guide further investigations.

Conclusions

Treatment with tadalafil 2.5 mg or 5 mg once daily was well tolerated and resulted in clinically important improvements in patients with mild (54.3% and 74.8%, respectively), moderate (51.3% and 63.1%, respectively), or severe (33.7% and 44.5%, respectively) ED.

Introduction

Phosphodiesterase type 5 inhibitors (PDE5-Is), such as tadalafil, sildenafil, and vardenafil, are recommended as first-line therapy for men with erectile dysfunction (ED) [1], [2]. The guidelines of the International Society for Sexual Medicine (ISSM) Standards Committee for Sexual Medicine suggest that treatment with PDE5-Is can be effective in the majority of ED etiologies except after severe damage of the parasympathetic cavernous nerves [3]. The relatively long half life of tadalafil (17.5 h) allowed the successful clinical development and subsequent regulatory approval of tadalafil 2.5 mg or 5 mg once daily, providing continuous PDE5 inhibition levels sufficient for ED treatment in the majority of patients [4], [5]. Data from long-term studies of up to 2 yr suggest tadalafil once daily provided efficacy for the duration of therapy [6].

Several factors can either cause or worsen ED, including aging, obesity, smoking, diabetes, cardiovascular diseases (CVDs), or use of certain medications [7], [8], [9], [10], [11]. Factors associated with ED in the European Male Aging Study were CVD, diabetes, obesity, lower urinary tract symptoms, and depression [12]. Men with ED and one of these characteristics may respond differently to tadalafil once-daily therapy.

This analysis pooled data from six double-blind, placebo-controlled, randomized trials to assess the efficacy and safety of tadalafil 2.5 mg and 5 mg once daily for the treatment of ED in relevant clinical subpopulations.

Section snippets

Study design and setting

Data were collected and pooled from six clinical studies (Table 1) [4], [5], [13], [14], [15], [16].

Patient population

Men aged ≥18 yr with a history of ED for ≥3 mo and a stable relationship were enrolled. Detailed inclusion/exclusion criteria have been published [4], [5], [13], [14], [15], [16]. Patients were randomly assigned to placebo (n = 596) or tadalafil at fixed doses of 2.5 mg (n = 394) or 5 mg (n = 923). Patients took the study drug once daily, preferably at the same time every day without regard to food

Baseline characteristics

Demographics and baseline characteristics for the integrated patient populations, stratified by treatment groups, are presented in Table 2. The mean age was 58 yr (range: 20.7–83.2 yr); 25.7% of the patients were aged ≥65 yr. A third of the patients were obese (BMI ≥30), >50% consumed alcohol, and >15% smoked. Nearly half of the total number of patients suffered from CVD, 28% had comorbid diabetes, and approximately 38% of all patients had hypertension. Nearly 90% had suffered from ED for at

Discussion

This analysis of data from 1913 men with ED demonstrated that tadalafil 2.5 mg and 5 mg once daily were effective in a variety of relevant patient subpopulations. In patients treated with placebo, IIEF-EF LS mean improvements did not reach the overall MCID threshold (≥4) in any of the subpopulations, in contrast to patients treated with tadalafil 2.5 mg or 5 mg once daily who experienced improvements reaching or superior to MCID in most clinical subpopulations examined, except for patients with BMI

Conclusions

Tadalafil 2.5 mg and 5 mg once daily were effective in improving erectile function. Of patients with mild, moderate, or severe ED at baseline, 74.8%, 63.1%, or 44.5%, respectively, reached severity-specific criteria for MCID and 66.1%, 48.0%, and 29.3%, respectively, reached IIEF-EF normalization following treatment with tadalafil 5 mg. Headache, nasopharyngitis, back pain, and dyspepsia were the most common side effects.

References (34)

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