ORIGINAL RESEARCH—PHARMACOTHERAPY
Efficacy and Safety of Oral Tadalafil in the Treatment of Men in Canada with Erectile Dysfunction: A Randomized, Double‐Blind, Parallel, Placebo‐Controlled Clinical Trial

https://doi.org/10.1111/j.1743-6109.2005.00097.xGet rights and content

ABSTRACT

Introduction

Erectile dysfunction (ED) is a highly prevalent, often undertreated condition.

Aim

This 12‐week, double‐blind, parallel, placebo‐controlled study was conducted at 25 sites in Canada to evaluate the efficacy and safety of oral tadalafil, a phosphodiesterase type 5 inhibitor, for the treatment of ED.

Methods

Men with ED of organic, psychogenic, or mixed etiology were stratified by baseline ED severity then randomly assigned to placebo (N = 50), tadalafil 10 mg (N = 103), or tadalafil 20 mg (N = 100), taken as needed (maximum, once daily).

Main Outcome Measures

Efficacy was assessed by the International Index of Erectile Function (IIEF), a Sexual Encounter Profile diary, and a global assessment question (GAQ).

Results

Tadalafil 10 mg and tadalafil 20 mg significantly improved erectile function compared with placebo (P < 0.001, all measures). At end point, the mean IIEF erectile function (EF) domain scores were 14.5, 21.2, and 23.3 of a possible score of 30 for placebo, tadalafil 10 mg, and tadalafil 20 mg, respectively. Patients treated with tadalafil reported greater change from baseline on the IIEF EF domain score compared with placebo, regardless of baseline ED severity. During treatment, the mean per‐patient proportion of successful intercourse attempts was higher for tadalafil 10 mg and 20 mg than for placebo (placebo, 31.9%; tadalafil 10 mg, 56.7%; and tadalafil 20 mg, 61.5%), and a greater proportion of patients reported improved erections with tadalafil (GAQ; placebo, 22.0%; tadalafil 10 mg, 67.0%; tadalafil 20 mg, 79.0%). Fifty percent and 62% of patients treated with tadalafil 10 mg and 20 mg, respectively, achieved successful sexual intercourse after their first dose, compared with 31% with placebo. Treatment‐emergent adverse events were generally mild or moderate.

Conclusion

Tadalafil was an effective, well‐tolerated therapy for ED of broad‐spectrum etiology and severity. Carrier S, Brock GB, Pommerville PJ, Shin J, Anglin G, Whitaker S, and Beasley CM Jr. Efficacy and safety of oral tadalafil in the treatment of men in Canada with erectile dysfunction: A randomized, double‐blind, parallel, placebo‐controlled clinical trial. J Sex Med 2005;2:685–698.

Introduction

Erectile dysfunction (ED), the inability to attain or maintain an erection sufficient for satisfactory sexual activities, has been estimated to affect as many as 3 million men in Canada and as many as 152 million men worldwide [1, 2, 3, 4]. Most men have an organic disorder with overlying psychogenic factors [5]. The prevalence and severity of ED increase with age and with conditions often associated with aging, such as depression, diabetes mellitus, hypertension, and cardiovascular disease [1, 3, 6]. ED lowers self‐esteem and diminishes quality of life in those affected by it [1, 7]. Although highly prevalent and distressing, ED is undertreated [8, 9, 10, 11]. Epidemiologic studies have shown that approximately 12% of patients with ED received therapy for the condition [8, 9]. With the availability of effective oral medication, the number of men seeking treatment for ED has increased. It is estimated that approximately 20% of men with ED may seek treatment annually [11]. Advances in the understanding of neurovascular mechanisms of sexual response and the development of new classes of drugs with therapeutic potential for the treatment of ED have heightened interest in sexual dysfunction [12].

Penile erection is mediated by neural stimuli that ultimately cause vasodilation of the arteries and sinusoidal spaces of the corpus cavernosum. As the arteries dilate, blood flow to the cavernosum increases. As the smooth muscle of the cavernosal sinusoidal spaces relaxes, draining veins are occluded and the cavernosum becomes engorged with blood leading to an erection [5, 13]. Nitric oxide, believed to play a central role in vasodilation of erectile tissues, relaxes smooth muscle by increasing guanylyl cyclase activity, which raises intracellular cyclic guanosine monophosphate (cGMP) concentrations [13]. Phosphodiesterase type 5 (PDE5) is the major cGMP hydrolysing enzyme in vascular smooth muscle, including human cavernosal smooth muscle [14]. PDE5 inhibition potentiates the relaxant effects of nitric oxide by inhibiting hydrolysis of cGMP, thereby increasing cGMP concentrations in the cell [15]. Sildenafil citrate was the first orally administered PDE5 inhibitor to be approved for the treatment of ED [16, 17, 18, 19, 20, 21, 22, 23].

Section snippets

Aim

Tadalafil (Cialis®, Lilly ICOS LLC, Bothell, WA and Indianapolis, IN), an orally administered PDE5 inhibitor, was recently approved for use as an ED treatment in Canada and the United States. It has a 17.5 hour half‐life in plasma. Tadalafil has demonstrated efficacy and safety in a global sample of men [24, 25, 26, 27]. The goal of this study was to evaluate the efficacy and safety of oral tadalafil, taken as needed, in men in Canada with ED of broad‐spectrum etiology (organic, psychogenic, or

Study Population

Men, at least 18 years of age, in a monogamous relationship with a female sexual partner, and with at least a 3‐month history of ED of organic, psychogenic, or mixed etiology, were recruited from 25 Canadian sites between October 2000 and April 2001. For this study, ED was defined as a consistent change in the quality of erection that adversely affected the patient's satisfaction with sexual intercourse. Patients agreed to make at least four sexual intercourse attempts prior to randomization

Efficacy

Efficacy assessments included the IIEF, a Sexual Encounter Profile (SEP) diary, and a global assessment question (GAQ). The IIEF, a 15‐item self‐administered questionnaire, assesses patient recall of erectile function over the previous 4 weeks. It is valid cross‐culturally and demonstrates adequate sensitivity and specificity for detecting treatment‐related changes in erectile function in patients with ED [29]. The IIEF was administered at the second study visit (baseline) and at each

Results

A total of 283 men entered the study; of these, 253 patients met the study criteria and were randomly assigned to treatment (placebo, N = 50; tadalafil 10 mg, N = 103; tadalafil 20 mg, N = 100). Of the 253 patients randomized (86.6%), 219 completed the study (Figure 1).

The baseline characteristics of patients randomly allocated to the three treatment groups were similar (Table 1). The mean age of the patients in each treatment group was approximately 59 years and the majority of patients were

Discussion

In this double‐blind, randomized, parallel, placebo‐controlled study, therapy with tadalafil significantly improved (P < 0.001) erectile function in men in Canada with mild to severe ED of broad‐spectrum etiology. Tadalafil 10 mg and tadalafil 20 mg were superior to placebo for all primary and secondary efficacy measures (P < 0.001, overall and pairwise comparisons). Furthermore, approximately 50% of patients treated with tadalafil 10 mg and tadalafil 20 mg attained no ED or normal erectile

Conclusion

In conclusion, therapy with oral tadalafil 10 mg and 20 mg, taken as needed, over a period of 12 weeks, without restrictions on food or alcohol intake, consistently enhanced erectile function, significantly improving patients’ ability to achieve and maintain erections. In this study, tadalafil was an effective, well‐tolerated therapy for men in Canada with mild to severe ED of broad‐spectrum etiology.

Acknowledgments

The authors would like to thank the investigators in this study: Randall P. Abele, MD, Edmonton, Alberta; Pierre Alarie, MD, Montreal, Quebec; Russell E. Albak, MD, Winnipeg, Manitoba; Robert B. Auld, MD, Halifax, Nova Scotia; Jack Barkin, MD, North York, Ontario; Richard Barr, MD, Calgary, Alberta; Wai‐Ling M. Baxter, MD, Edmonton, Alberta; Kerry Beale, MD, Burlington, Ontario; Guy Belair, MD, Montreal, Quebec; Andre Bilodeau, MD, Quebec City, Quebec; Edwin R. Brankston, MD, Courtice, Ontario;

Conflict of Interest

Dr. Anglin and Ms. Shin are employees of Eli Lilly Canada, Dr. Whitaker is an employee of ICOS Corporation, and Dr. Beasley is an employee of Eli Lilly and Company, U.S.A.

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