Efficacy and safety of simenafil in men with erectile dysfunction: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group, phase 3 trial

Background: Simenafil, a potent and highly selective oral phosphodiesterase type 5 (PDE5) inhibitor, is currently under investigation for erectile dysfunction (ED) treatment. Aims: To evaluate the efficacy and safety of simenafil for ED treatment. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel group, phase 3 study in men aged 18-75 years with a history of ED of 6 months or more. The subjects were randomized in a ratio of 1:1:1:1 to on-demand receive fixed-dose either placebo or simenafil (2.5 mg, 5 mg or 10 mg) for 12 weeks. Outcomes: Primary efficacy endpoints were the least square mean (LSM) changes from baseline to week 12 in the erectile function (EF) domain of the International Index of Erectile Function (IIEF), percentages of "yes" responses to sexual encounter profile (SEP) diary question 2 (SEP Q2: Were you able to insert your penis into your partner's vagina?) and question 3 (SEP Q3: Did your erection last long enough for you to have successful intercourse?) Results: A total of 765 patients were randomized and 92.3% completed the study. The mean age of subjects was 41.3 years and 81.6% had moderate to severe ED (mean overall International Index of Erectile Function-Erectile Function (IIEF-EF) domain score 13.4). After 12 weeks of treatment, doses of 2.5, 5, and 10 mg of simenafil exhibited substantial increases than placebo in IIEF-EF score (12.3, 12.3, 12.7 vs. 9.6), the percentages of "yes" responses to SEP Q2 (40.58%, 42.43%, 43.98% vs. 32.05%), and SEP Q3 (61.91%, 63.70%, 65.19% vs. 46.70%) (all P < .001). Adverse drug reactions (ADRs) occurred in 36.2% of patients who received simenafil (32.6% in simenafil 5 mg group, the clinically recommended dose) and in 30.9% of those who received placebo. The most common (>= 2%) ADRs were dizziness, headache, flushing, nasal congestion, and dry mouth, and most were mild or moderate. Furthermore, abnormal vision (PDE6 related) and myalgia (PDE11 related) did not occur in patients who received simenafil. Clinical Implications: Simenafil is highly effective in all 3 dose groups and has a low effective dose and good safety profile, providing a novel, favorable treatment option for patients with ED. Strengths and Limitations: The efficacy and safety evaluation of simenafil in difficult-to-treat patients with ED, ED patients with other concomitant diseases, and other ethnic populations was not performed. Conclusion: Simenafil is an effective and well-tolerated therapy for patients with ED.