A placebo-controlled study investigating the efficacy and safety of the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of men with lower urinary tract symptoms associated with clinical benign prostatic hyperplasia

Objectives: To evaluate the efficacy and safety of the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in men with and without erectile dysfunction (ED).

Patients and methods: This was a multicentre, double-blind, placebo- and active-controlled, parallel-group study conducted across 45 centres in North and South America, Europe, and Australia. In all, 418 men aged ≥ 40 years with a clinical diagnosis of BPH, an International Prostate Symptom Score (IPSS) of ≥ 13, and maximum urinary flow rate (Q(max) ) of 5-15 mL/s for a voided volume of > 150 mL were stratified into two groups (with and without ED) and randomized to one of seven treatment groups, i.e. UK-369,003 at 10, 25, 50 or 100 mg modified release (MR), UK-369,003 40 mg immediate release (IR), tamsulosin 0.4 mg prolonged release, or placebo, for 12 weeks. The primary study endpoint was the change in total IPSS after 12 weeks of treatment. Secondary efficacy measures were IPSS storage and voiding subscores, Q(max) , International Index of Erectile Function-Erectile Function domain, questions 5 and 6 of the Quality of Erection Questionnaire, the International Consultation on Incontinence Questionnaire-Male LUTS, the patient-reported treatment-impact questionnaire, and a bladder diary in which patients recorded the number of voluntary urinary voids, volume of urine voided per micturition, leaks, and urgency episodes.

Results: The mean change in the IPSS from baseline at week 12 for UK-369,003 100 mg MR and 40 mg IR was -2.91 and -2.50 better than placebo, respectively. There was increasing efficacy with increasing dose of the MR formulation. For UK-369,003 100 mg MR, Q(max) improved by 2.10 mL/s compared with 0.84 mL/s in the placebo group.

Conclusions: UK-369,003 had clinically meaningful efficacy and was well tolerated in men with LUTS associated with BPH. The Bayesian statistical analysis gave high posterior probabilities for true differences between UK-369,003 100 mg MR and placebo. There was greater preference, satisfaction and willingness to use UK-369,003 again for all treatment groups compared with placebo.