Tadalafil 2.5 or 5 mg Administered Once Daily for 12 Weeks in Men with Both Erectile Dysfunction and Signs and Symptoms of Benign Prostatic Hyperplasia: Results of a Randomized, Placebo-Controlled, Double-Blind Study

Abstract

Introduction Erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS) commonly coexist in aging men. Tadalafil, a phosphodiesterase type 5 inhibitor approved for treating ED, is currently being evaluated for treating BPH-LUTS. Aims This multinational Phase 3 study assessed effects of tadalafil 2.5 or 5 mg once daily on ED and BPH-LUTS in men with both conditions during 12 weeks of double-blinded therapy. Methods Men were ≥45 years old, sexually active, and experiencing ED for ≥3 months and BPH-LUTS for >6 months. Randomization (baseline) followed a 4-week placebo lead-in; changes from baseline were assessed via analysis of covariance and compared to placebo. A gatekeeping procedure controlled for multiple comparisons of co-primary and key secondary measures at end point (last post-baseline observation). Main Outcome Measures The co-primary measures were the International Index of Erectile Function-erectile function (IIEF-EF) domain and International Prostate Symptom Score (IPSS) score; key secondary measures were the Sexual Encounter Profile Question 3 (SEP Q3) and BPH Impact Index (BII). Treatment-emergent adverse events, serious adverse events, orthostatic vital signs, clinical laboratory and uroflowmetry parameters, and postvoid residual volume were assessed. Results Tadalafil 2.5 mg (N = 198) and 5 mg (N = 208) significantly improved IIEF-EF domain scores (both P < 0.001) vs. placebo (N = 200) at end point. For IPSS, improvements were significant with tadalafil 5 mg (P < 0.001), but not 2.5 mg, for observations from 2 weeks through end point (least-squares mean ± standard error change from baseline at end point, placebo −3.8 ± 0.5, tadalafil 2.5 mg −4.6 ± 0.4, and 5 mg −6.1 ± 0.4). Tadalafil 5 mg significantly improved SEP Q3 and BII (P < 0.001). Overall, tadalafil was well tolerated with no clinically adverse changes in orthostatic vital signs or uroflowmetry parameters. Conclusions Tadalafil 5 mg significantly improved both ED and BPH-related outcomes through 12 weeks and was well tolerated.

Tadalafil 5 mg once daily for the treatment of Asian men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: Analyses of data pooled from three randomized, double‐blind, placebo‐controlled studies

“…[14][15][16] The results from these three Asian studies were also comparable with pivotal clinical studies of tadalafil in American and European men with BPH/LUTS. [17][18][19][20][21][22] The incidence/severity of BPH/LUTS has been shown to increase with increasing age; additionally, LUTS patients experience varying degrees of symptom severity, have comorbid conditions, or have prior exposure to BPH treatments, all of which might impact the efficacy of new therapies. [23][24][25] As individual studies, the three aforementioned trials were insufficiently powered to analyze patient subgroups.…”

Benign prostatic hyperplasia and lower urinary tract symptom guidelines

“…18 Research among men with or without erectile dysfunction (ED) and LUTS has shown that tadalafil has a beneficial effect on LUTS independent of the drug's benefit on ED. [19][20][21][22][23] Indeed, a head-to-head comparison of tadalafil with the alpha-blocker tamsulosin showed similar improvements of LUTS due to BPH with each agent.…”

Treatment of benign prostatic hyperplasia

“…23 (A) Since iPDE5 is indicated for the treatment of erectile dysfunction, this class of medication may be an option in the treatment of patients presenting both disorders. 22,23,26 (A)…”

“…This indication is based on double-blind randomized placebo-controlled trials (RCT), that showed a significant reduction of I-PSS after twelve weeks. 22,23,26,27 (A) A prospective placebo-controlled study of tadalafil with tamsulosin used as an active comparator showed that tadalafil led to a decrease in tamsulosin-like I-PSS as early as week 1. 23 (A) Since iPDE5 is indicated for the treatment of erectile dysfunction, this class of medication may be an option in the treatment of patients presenting both disorders.…”

“…[21][22][23][24] (A) The likely mechanisms of action stem from effects on smooth muscle relaxation, endothelial cell proliferation, improved blood flow, and activity on the prostatic efferent nerves. 25 (D) Currently, tadalafil (5 mg once daily) is approved in Brazil for the treatment of urinary symptoms associated with BPH.…”