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Introduction Mirodenafil is a newly developed oral phosphodiesterase type 5 inhibitor, currently under investigation as a treatment for erectile dysfunction (ED). Aim We investigated the efficacy and safety of on demand mirodenafil therapy at fixed doses (50 and 100 mg) in Korean men with a broad range of ED. Methods A multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted with 223 subjects who were randomized to placebo or mirodenafil at fixed doses of 50 or 100 mg for 12 weeks on an “as needed” basis. Main Outcome Measures Primary efficacy measures were scores on the International Index of Erectile Function (IIEF) Question 3 (Q3) and Question 4 (Q4). Secondary efficacy measures included all domain scores of the IIEF, Sexual Encounter Profile Question 2 (SEP2), Sexual Encounter Profile Question 3 (SEP3), the Global Assessment Question (GAQ), and the Life Satisfaction Checklist (LSC). Safety assessments included laboratory tests, vital signs, physical examination, 12-lead electrocardiogram recordings, and patients’ reporting of adverse events. Results Mirodenafil 50 and 100 mg groups showed a significantly greater increase in IIEF Q3 (P = 0.0001, P < 0.0001, respectively) and Q4 scores (both P < 0.0001) at the end point compared with the placebo group. And mirodenafil in both doses significantly improved the scores of all five domains of the IIEF, SEP2, and SEP3 as well as the percentages of patients responding positively to the GAQ compared with the placebo group. As for LSC scores, the two mirodenafil groups showed significantly greater improvements in items regarding life as a whole, sexual life, and partner relationship than the placebo group. Most treatment-associated adverse events were of mild intensity, resolving spontaneously. Conclusions Mirodenafil, in doses of 50 or 100 mg, significantly improved erectile function and were well tolerated in a representative population of Korean men with broad-spectrum ED of various etiologies and severities.

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Avanafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for treating erectile dysfunction (ED). Preclinical and clinical phase I studies showed that avanafil had enhanced selectivity, faster onset of action and a favourable side‐effect profile relative to currently available PDE5 inhibitors. As the result of phase III clinical trial for the efficacy and safety of avanafil treatment (100 and 200 mg), taken as needed over a period of 12 weeks, in Korean patients with ED, avanafil is an effective and well‐tolerated therapy for ED of broad‐spectrum aetiology and severity. OBJECTIVE To evaluate the efficacy and safety of avanafil, a new potent selective phosphodiesterase type 5 (PDE5) inhibitor, in patients with erectile dysfunction (ED). PATIENTS AND METHODS The present study was a multicentre, randomized, double‐blind, placebo‐controlled, fix‐dosed phase three clinical trial involving 200 patients with ED. The subjects were treated with placebo or avanafil (100 or 200 mg) for 12 weeks and were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ). The primary outcome variable was the change from baseline for IIEF erectile function domain (EFD) score. The secondary outcome variables were SEP Q2 and Q3, the shift to normal rate (EFD ≥ 26), and response to the GAQ. RESULTS Compared with placebo, patients who took 100 or 200 mg of avanafil had significantly improved IIEF‐EFD score. There were similar results when comparing Q2 and Q3 in the SEP diary and the GAQ. Flushing was the most common treatment‐related adverse event. Most adverse events were transient and mild or moderate in severity. CONCLUSION Avanafil is an effective and well‐tolerated therapy for ED of broad‐spectrum aetiology and severity.

Introduction Mirodenafil is a recently developed oral phosphodiesterase type 5 inhibitor, which was observed to significantly improve erectile function and was well tolerated in men with broad-spectrum erectile dysfunction (ED). Aim To investigate the efficacy and safety of mirodenafil treatment compared with placebo in men taking at least one antihypertensive medication. Methods A multicenter, double-blind, placebo-controlled, parallel group, fixed-dose study was conducted with 109 subjects who were randomized to placebo or mirodenafil 100 mg for 12 weeks on an “as needed” basis. Main Outcome Measures The primary efficacy measures were the changes from baseline in sum of scores on International Index of Erectile Function-erectile function domain (IIEF-EF) questions 1 to 5 and 15 with treatment. The secondary efficacy measures included scores on IIEF question 3 and 4 (Q3 and Q4), all domain scores of IIEF, and Sexual Encounter Profile Question 2 and 3 (SEP2 and SEP3) along with responses to Global Assessment Question (GAQ) and Life Satisfaction Checklist (LSC). The safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients’ reporting of adverse events. Results The mirodenafil group showed significantly greater increase in IIEF-EF scores at 12 weeks compared with the placebo group (9.35 ± 6.86 vs. 2.66 ± 6.44, P <0.001). The mirodenafil group also demonstrated significantly greater improvement in scores of IIEF Q3 and Q4, other four domains of IIEF, SEP2, SEP3, and LSC along with percentages of patients responding positively to GAQ compared with the placebo group. During the study, no clinically significant changes were observed regarding blood pressure, heart rate, electrocardiographic findings, or laboratory values. Facial flushing and headache were the most common treatment-associated adverse events, which were mild or moderate in severity, resolving spontaneously. Conclusions Mirodenafil was effective and safe in men with ED concomitantly taking antihypertensive medications.

Obesity is a major public health issue worldwide and is frequently associated with erectile dysfunction (ED). Both conditions may share an internal pathologic environment, also known as common soil. Their main pathophysiologic processes are oxidative stress, inflammation, and resultant insulin and leptin resistance. Moreover, the severity of ED is correlated with comorbid medical conditions, including obesity. Therefore, amelioration of these comorbidities may increase the efficacy of ED treatment with phosphodiesterase 5 inhibitors, the first-line medication for patients with ED. Although metformin was originally developed as an insulin sensitizer six decades ago, it has also been shown to improve leptin resistance. In addition, metformin has been reported to reduce oxidative stress, inflammatory response, and body weight, as well as improve ED, in animal and human studies. Moreover, administration of a combination of metformin and phosphodiesterase 5 inhibitors improves erectile function in patients with ED who have a poor response to sildenafil and are insulin resistant. Thus, concomitant treatment of metabolic derangements associated with obesity in patients with ED who are obese would improve the efficacy and reduce the refractory response to penile vasodilators. In this review, we discuss the connecting factors between obesity and ED and the possible combined treatment modalities.