ORIGINAL RESEARCH—PHARMACOTHERAPY
The Efficacy of Tadalafil in Clinical Populations

https://doi.org/10.1111/j.1743-6109.2005.00068.xGet rights and content

ABSTRACT

Objectives

To evaluate the efficacy of tadalafil in men with erectile dysfunction (ED) by demographic and ED characteristics, in patients having various comorbid medical conditions, and in patients receiving drug treatment for other medical conditions.

Methods

This is an analysis of 11 double‐blind, placebo‐controlled trials with 2,102 men with a broad spectrum of ED etiology and various comorbid medical conditions as participants. The variables analyzed in this report included race, age, body mass index (BMI), ED etiology, ED severity, ED duration, smoking, prior sildenafil use, presence of comorbid conditions (diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, depression, benign prostatic hyperplasia), and treatment with antihypertensives or antidepressants. Patients were randomly assigned to receive tadalafil 10 mg (N = 321), tadalafil 20 mg (N = 1,143), or placebo (N = 638). The primary efficacy variables included mean changes from baseline in the erectile function (EF) domain score of the International Index of Erectile Function (IIEF) questionnaire, and the mean per‐patient percentage of “yes” responses to the Sexual Encounter Profile (SEP) diary question 3 (SEP3––successful intercourse). The Global Assessment Question 1 (GAQ) was evaluated, as was the percentage of men attaining a normal IIEF EF domain score at end point.

Results

Patients taking tadalafil 10 mg or 20 mg demonstrated significant improvement (P < 0.005) from baseline to end point on the IIEF EF domain score in all subpopulations analyzed compared with patients receiving placebo. The mean‐per‐patient percentage of “yes” responses to SEP3 increased significantly in all subpopulations taking tadalafil compared with placebo (P < 0.05). Tadalafil‐treated patients had a significantly greater positive response rate on the GAQ in all subpopulations analyzed compared with placebo‐treated patients (P < 0.03) except for the tadalafil 10 mg cardiovascular subpopulation (placebo, 46.8%; tadalafil 10 mg, 71.0%; P = 0.127). The percentage of positive responses ranged from 72% to 91% for patients on tadalafil 20 mg and from 52% to 94% for tadalafil 10 mg compared with a range of 20% to 47% for placebo‐treated patients.

Conclusions

Tadalafil was effective in improving erectile function across a wide spectrum of ED patients including patients with various comorbid conditions.

Introduction

Erectile dysfunction (ED) has become recognized as a significant health issue in a large percentage of men over the age of 40 years [1]. A number of factors can contribute to the development of ED, including aging, cardiovascular disease, diabetes, smoking, anxiety and/or depression, certain drugs including antidepressants and antipsychotics [2], and a variety of other organic or psychological factors [3, 4, 5]. Awareness of ED increased with the approval in 1998 of sildenafil citrate, an oral treatment that improves erectile function in men having ED of various etiologies [6, 7].

Tadalafil and sildenafil are inhibitors of phosphodiesterase type 5. Tadalafil primarily differs from sildenafil by having a duration of efficacy lasting up to 36 hours after a single dose compared with  about  4 hours  for  sildenafil [8, 9],  although  a recently published small open‐label study in sildenafil responders suggested that sildenafil 100 mg might be effective in some men up to 12 hours after dosing [10]. Tadalafil has been shown to be efficacious and safe in a large number of patients with ED including men with diabetes mellitus [11, 12, 13, 14]. Additionally, a recent study demonstrated that tadalafil significantly improved erectile function in men with ED following bilateral nerve‐sparing radical retropubic prostatectomy [15]. In this article, 11 double‐blind placebo‐controlled trials were integrated and analyzed to determine the effectiveness of tadalafil in improving erectile function in more than a dozen clinical subpopulations.

Section snippets

Study Design

Data collected from 11 randomized, double‐blind, placebo‐controlled, parallel trials conducted worldwide at 174 centers in 18 countries from April 1999 to February 2003 were used in all of the analyses (Table 1). Details regarding the general study design, efficacy and safety measures, and statistical analysis were published previously [12, 13]. Patients were randomized to 12 weeks of treatment with placebo (N = 638) or tadalafil at fixed doses including 10 mg (N = 321) or 20 mg (N = 1,143)

Demographic and Baseline Characteristics

Demographic and baseline illness characteristics are shown in Table 2. The mean age was 56 years (range, 22–88 years) with most patients (88%) having ED for at least 1 year. The proportion of patients with mild, moderate, or severe ED was similar in all three treatment groups (P = 0.933). Hypertension (29%), diabetes mellitus (20%), and hyperlipidemia (16%) were common comorbid conditions.

The vast majority of patients taking tadalafil (10 mg, 88.5%; 20 mg, 89.7%) and placebo (86.8%) completed

Discussion

This analysis of 2,102 men with ED demonstrated that tadalafil 10 mg and 20 mg were effective in all clinical populations analyzed, including in patients with diabetes mellitus, who are considered difficult to treat. Tadalafil 20 mg showed numerically greater  improvement  than  tadalafil  10 mg  for each efficacy measure in most of the clinical populations.

Tadalafil showed improved efficacy among all racial groups. It would have been more informative if the number of Hispanics and patients of

Conclusions

The findings from this 11‐study integrated analysis of 2,102 men with ED demonstrate that tadalafil is effective in improving erectile function across a variety of patient demographics and illness characteristics including ED etiology, severity and duration, and comorbid conditions and treatments. Tadalafil also proved to be effective in the subpopulation of men with diabetes mellitus and ED, who are difficult to treat.

Conflict of Interest

Wei Christine Wang, Wei Shen, Daniel J. Walker, David G. Wong, and Sanjeev Ahuja are employees of Eli Lilly and Company.

References (39)

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  • Phosphodiesterase type 5 inhibitors for treating erectile dysfunction and lower urinary tract symptoms secondary to benign prostatic hyperplasia: A comprehensive review

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    The objective of using on-demand PDE5 inhibitors is to treat ED independently of BPH symptoms. In an analysis of 11 double-blind, placebo-controlled trials on the efficacy of tadalafil, Lewis et al. [22] showed that tadalafil 20 mg significantly improved erectile function in men with ED who had BPH as a comorbid condition. Specifically, the change from baseline in the least-squares mean International Index of Erectile Function (IIEF) [23] erectile function (EF) domain scores was significantly more pronounced for men treated with tadalafil 20 mg than for men treated with placebo (8.4 vs. 1.1, P < 0.001; scores at the endpoint were 22.6 and 15.4, respectively).

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    The magnitude of separation and level of discrimination of treatment effects we observed provide strong support for our proposed definition, which may be of value for clinicians, researchers, and regulators concerned with assessing clinically meaningful response to treatment in practice or clinical trial settings. In addition to showing the discriminant validity of the new classification, we aimed to examine the convergent validity of our classification by assessing agreement with known and accepted measures such as the SEP 3 [12] and GAQ measure [6,7]. Using these measures, we showed strong convergent validity with high levels of agreement not accounted for by the effects of covariates such as aging.

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