Abstract
OBJECTIVES: To evaluate the efficacy and safety of a fixed-dose combination (FDC) of dutasteride and tadalafil vs monotherapy in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: This phase III trial enrolled 667 patients. After screening and washout, eligible patients were stratified by the baseline International Prostate Symptom Score (IPSS) and randomised (1:1:1) to receive FDC dutasteride 0.5 mg/tadalafil 5 mg (FDC 0.5/5 mg), dutasteride 0.5 mg, or tadalafil 5 mg for 48 weeks. The primary endpoint was the change in total IPSS from baseline to Week 48. Efficacy and safety were assessed at 4, 12, 24, 36, and 48 weeks. RESULTS: In total, 619 patients were analysed for efficacy. The least squares (LS) mean (standard error [se]) change in total IPSS at 48 weeks from baseline was -9.49 (0.37) for the FDC 0.5/5 mg group vs -4.40 (0.37) for dutasteride 0.5 mg group (LS mean difference [LSMD] -5.09, 95% confidence interval [CI] -6.13 to -4.50; P < 0.001), and -9.53 (0.36) for the FDC 0.5/5 mg group vs -4.24 (0.37) for tadalafil 5 mg group (LSMD -5.29, 95% CI -6.30 to -4.27; P < 0.001). The FDC 0.5/5 mg group demonstrated the most pronounced improvement in quality of life. Although the maximum urinary flow rate and post-void residual volume improved in all groups, differences were not statistically significant. In the comparison between the FDC 0.5/5 mg and dutasteride 0.5 mg groups, the LSMD (95% CI) of change from baseline to Week 48 in the international index of erectile function - erectile function (IIEF - EF) total score was 4.03 (2.35 to -5.71) (P < 0.05). Among the 655 patients analysed for safety, treatment-emergent adverse events occurred in 32.88% (FDC 0.5/5 mg) vs 21.20% (dutasteride 0.5 mg) and 26.48% (tadalafil 5 mg), with few serious adverse events observed. CONCLUSIONS: The FDC 0.5/5 mg demonstrated superior efficacy, and an acceptable safety profile compared with dutasteride and tadalafil monotherapies in patients with BPH.