Introduction

Lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are commonly occurred in aged men and known to be mechanistically associated each other. The aim of this study was to evaluate the efficacy and safety of once-daily fixed dose combination (FDC) of tamsulosin and tadalafil in patients with BPH and ED in comparison to tadalafil mono-therapy.

Methods

In a phase III, multi-center, randomized, double-blinded and placebo-controlled clinical trial, participants were randomly assigned to active treatment groups of either FDCs consisting tamsulosin 0.4 or 0.2mg in combination of tadalafil 5mg or mono-component of tadalafil 5mg for 12-week treatment period, followed by an open-label extension period that continued up to week 24, while being treated with FDC of tamsulosin 0.4 mg and tadalafil 5mg. The primary efficacy variables of the study were assessed after 12 weeks of treatment using the international prostate symptom score (IPSS) and International Index of Erectile Function (IIEF). Other assessments included Sexual Encounter Profile, Global Assessment Question, Qmax, PSA, and PVR at every visit with four- or six-week interval. Eligible patients were men aged over 45 years with BPH confirmed by total IPSS greater than or equal to 13 and ED persistent for longer than 3 months.

Results

Total 510 subjects were enrolled. The mean decrease from baseline in total IPSS at week 12 of the treatment period was significantly greater in the FDC of tamsulosin 0.4 mg group compared to the tadalafil 5mg group (p=0.0320). The lower limit of one-sided 97.5% confidence interval of changes from baseline in IIEF-Erectile Function (EF) domain score was greater than the pre-specified non-inferiority margin (-3.22) for both FDCs of tamsulosin 0.4 and 0.2mg. Treatment change from tadalafil 5 mg mono-therapy to FDC of tamsulosin 0.4mg and tadalafil 5mg made significant improvement in total IPSS at week 24 of the extension period after treatment change at week 12 (p<0.0001). The most frequent adverse drug reactions included headache, flushing, nasal congestion and ocular hyperaemia, all of which were of mild or moderate intensity and both FDCs of tamsulosin 0.4 and 0.2mg were well tolerated.

Conclusions

The FDC of tadalafil 5mg and tamsulosin 0.4mg substantiated superiority for BPH/LUTS treatment and non-inferiority for ED treatment over tadalafil 5mg mono-therapy without showing any clinically significant safety issues, supporting favorable benefit-risk balance of the FDC for the treatment of comorbid BPH and ED.

Funding

Hanmi Pharmaceutical Co., Ltd., Seoul, Korea