Tadalafil Administered Once Daily for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Dose Finding Study

Purpose

Phosphodiesterase type 5 inhibitors are widely used to treat erectile dysfunction. Preliminary data have suggested phosphodiesterase type 5 inhibitor efficacy in men with lower urinary tract symptoms associated with clinical benign prostatic hyperplasia.

Materials and Methods

After a 4-week placebo run-in period 1,058 men with benign prostatic hyperplasia lower urinary tract symptoms were randomly allocated to receive 12-week, once daily treatment with placebo or tadalafil (2.5, 5, 10 or 20 mg).

Results

The International Prostate Symptom Score least squares mean change from baseline to end point was significantly improved for 2.5 (−3.9, p = 0.015), 5 (−4.9, p <0.001), 10 (−5.2, p <0.001) and 20 mg (−5.2, p <0.001) tadalafil compared to placebo (−2.3). International Prostate Symptom Score improvements at 4, 8 and 12 weeks were significant for all tadalafil doses and they demonstrated a dose-response relationship. Tadalafil (2.5 mg) significantly improved the International Prostate Symptom Score obstructive subscore and the International Index of Erectile Function-Erectile Function domain, the latter in sexually active men with a history of erectile dysfunction. Statistically significant improvements were noted for 5, 10 and 20 mg tadalafil compared to placebo, as assessed by the International Prostate Symptom Score irritative and obstructive subscores, International Prostate Symptom Score Quality of Life, Benign Prostatic Hyperplasia Impact Index (nonsignificant for 10 mg), Global Assessment Question and International Index of Erectile Function-Erectile Function domain. No statistically significant effect of treatment compared to placebo was noted for peak flow at any tadalafil dose. Treatment emergent adverse events were infrequent in all tadalafil groups.

Conclusions

Once daily tadalafil demonstrated clinically meaningful and statistically significant efficacy and it was well tolerated in men with benign prostatic hyperplasia lower urinary tract symptoms. Of the doses studied 5 mg tadalafil appeared to provide a positive risk-benefit profile.

Key Words: prostate, tadalafil, dose-response relationship, drug, prostatic hyperplasia, questionnaires

Abbreviations and Acronyms: AE, adverse event, BPH, benign prostatic hyperplasia, BPH-II, BPH Impact Index, ED, erectile dysfunction, GAQ, Global Assessment Question, IIEF, International Index of Erectile Function, IIEF-EF, IIEF Erectile Function domain, I-PSS, International Prostate Symptom Score, LUTS, lower urinary tract symptoms, PDE5, phosphodiesterase type 5, PSA, prostate specific antigen, PVR, post-void residual urine, Qmax, peak urinary flow rate, QOL, quality of life, SAE, serious AE, TEAE, treatment emergent AE