Dae Yul Yang

Efficacy and Safety of Once-Daily Dosing of Udenafil in the Treatment of Erectile Dysfunction: Results of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND A once-daily dosing regimen with a phosphodiesterase type 5 inhibitor is needed for the treatment of erectile dysfunction (ED), in part because of the behavioral complexities associated with sexual intimacy. Many patients prefer spontaneous rather than scheduled sexual activities or they anticipate frequent sexual encounters. The pharmacokinetic profiles of udenafil with a time of maximal concentration of 1.0-1.5h and a terminal half-life of 11-13 h make udenafil a good candidate for once-daily dosing. OBJECTIVE To evaluate the efficacy and safety of once-daily dosing of udenafil in the treatment of ED. DESIGN, SETTING, AND PARTICIPANTS This multicenter randomized double-blind, placebo-controlled, fix-dosed clinical trial involved 237 patients with ED. The subjects, who were treated with placebo or udenafil (25mg, 50mg, or 75 mg) once daily for 12 wk, were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ) during the study. MEASUREMENTS The primary outcome parameter was the change from baseline for the IIEF erectile function domain (EFD) score. The secondary outcome parameters were SEP questions 2 and 3, the shift to normal rate (EFD ≥ 26), and the response to the GAQ. RESULTS AND LIMITATIONS Compared with placebo, patients who took 50mg or 75 mg of udenafil had a significantly improved IIEF-EFD score. Similar results were observed in comparing questions 2 and 3 in the SEP diary and the GAQ. Flushing was the most common treatment-related adverse event, which was transient and mild to moderate in severity. CONCLUSIONS Udenafil significantly improved erectile function among ED patients when administered in doses of 50mg or 75 mg once daily for 12 wk. Daily administration of udenafil (50mg) may be another treatment option for ED.

Stent Position Is More Important than α-Blockers or Anticholinergics for Stent-Related Lower Urinary Tract Symptoms after Ureteroscopic Ureterolithotomy: A Prospective Randomized Study

Purpose To evaluate the clinical factors that impact ureteral stent-related lower urinary tract symptoms (LUTS) after ureteroscopic ureterolithotomy, including the stent position and medication. Materials and Methods Fifty-three patients who underwent ureteroscopic ureterolithotomy with indwelling a stent were distributed into three groups. On demand analgesics were given to the group 1 (n=18). Daily tamsulosin 0.2 mg was added for group 2 (n=15) and daily tamsulosin 0.2 mg and tolterodine 4 mg was added for group 3 (n=20). The patients were also subclassified into appropriate or inappropriate group according to stent position. All the patients completed a visual analogue scale (VAS) and International Prostate Symptom Score (IPSS) on the 1st and 7th postoperative days. The VAS and IPSS were analyzed according to the medication groups and the stent position. Results In the appropriate stent potion group, only the storage symptom scores of groups 2 and 3 on the 1st postoperative day were significantly lower than those of the group 1 (p=0.001). This medication effect on LUTS was not observed in the inappropriate stent position group. In this group, total IPSS (p=0.015) and storage symptom scores (p=0.002) were higher than in the appropriate stent position group on the 7th postoperative day. Conclusions Correct placement of the stent was more important than medication for lessening stent-related storage symptoms.

Efficacy and safety of avanafil for treating erectile dysfunction: results of a multicentre, randomized, double‐blind, placebo‐controlled trial

Study Type – Therapy (RCT)

Comparison Between On‐Demand Dosing of Dapoxetine Alone and Dapoxetine Plus Mirodenafil in Patients with Lifelong Premature Ejaculation: Prospective, Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Study

INTRODUCTION There is partial evidence to support the use of phophodiesterase-5 inhibitor (PDE5-I) for the treatment of premature ejaculation (PE). AIM We compared on-demand dosing of dapoxetine alone and combined with mirodenafil in subjects with lifelong PE and without erectile dysfunction (ED). METHODS Our prospective, randomized, double-blind, placebo-controlled, multicenter trial enrolled 118 subjects with lifelong PE without ED. PE was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision. Patients were divided into two groups: dapoxetine 30 mg plus placebo (group A, n=56) and dapoxetine 30 mg plus mirodenafil 50 mg (group B, n=62). MAIN OUTCOME MEASURES During 12 weeks, intravaginal ejaculatory latency time (IELT) and the time from foreplay to beginning intercourse (FTIT) with a stopwatch, and Premature Ejaculation Profile (PEP) were measured. Overall sexual act time (OSAT; sum of FTIT and IELT) was calculated. Any treatment-emergent adverse events (TEAEs) were also recorded. RESULTS Over 12 weeks, IELT, OSAT, and PEP index score significantly improved in group B compared with group A (increased geometric mean IELT in group A and B=3.6 and 6.1 minutes, P=0.026; increased geometric mean OSAT in group A and B=5.5 and 9.9 minutes, P=0.012; increased median PEP index score in group A and B=1.0 and 1.3, P=0.046). However, there was no significant difference between two groups with respect to improvement of FTIT (P=0.147). TEAEs did not differ between groups (all P>0.05), and there was no serious adverse event in any subjects. CONCLUSIONS Low dose of dapoxetine combined with mirodenafil showed better results in terms of IELT, OSAT, and PEP index score, and similar TEAEs, compared with that of dapoxetine only. Our results support the suggestion that the PDE5-Is have a potential role in the treatment of PE without ED.

A Therapeutic Confirmatory Study to Assess the Safety and Efficacy of Zydena® (Udenafil) for the Treatment of Erectile Dysfunction in Male Patients with Diabetes Mellitus

INTRODUCTION Patients with diabetes mellitus (DM) are reported to experience more severe erectile dysfunction (ED) symptoms and respond less to ED treatments compared with patients with ED of other etiologies. AIM This study was undertaken to evaluate the safety and efficacy of udenafil for the treatment of ED in a larger number of patients with DM. METHODS A placebo-controlled, randomized, double-blind, double-dummy, parallel-group design multicenter study, fixed-dose trial was conducted. The trial involved seven study sites in Korea, with 174 ED patients with DM. The subjects, treated with placebo, 100 mg, or 200 mg of udenafil for 12 weeks, were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Question (GAQ) during the study period. MAIN OUTCOME MEASURES The primary efficacy parameter was the change in the erectile function domain (EFD) score of IIEF from baseline. Secondary parameters were IIEF questions 3 (Q3) and Q4, SEP Q2 and Q3, rate of achieving normal erectile function (EFD ≥ 26), and the response to GAQ. RESULTS Compared with the placebo, patients receiving both doses of udenafil showed statistically significant improvements in the IIEF-EFD score, respectively. However, statistically significant difference was not observed between the udenafil 100 mg and the udenafil 200 mg groups. Similar results were observed in the comparison of Q3 and Q4 of IIEF, SEP diary, and GAQ. The percentages of subjects experiencing at least one adverse event related to the study drugs were 3.6%, 15.8%, and 22.4% for the placebo, udenafil 100 mg, and udenafil 200 mg groups, respectively. However, these events were all mild in severity. Major adverse events were flushing, headache, nausea, and conjunctival hyperemia. CONCLUSION Udenafil was significantly effective for the treatment of ED, demonstrating statistically significant improvement in erectile function in patients with DM. The incidence of adverse events was relatively low and well tolerated in patients with DM.

Spontaneous Recovery of Cavernous Nerve Crush Injury

Purpose To investigate pathophysiological consequences and spontaneous recovery after cavernous nerve crush injury (CNCI) in a rat model. Materials and Methods Twenty 4-week-old male Sprague-Dawley rats were divided into the following groups: sham-operated group (n=10) and bilateral CNCI groups (n=10) for two different durations (12 and 24 weeks). At both time points, CN electrical stimulation was used to assess erectile function by measuring the intracavernous pressure. The expression of hypoxia inducible factor (HIF)-1α and sonic hedgehog (SHH) was examined in penile tissue. Immunohistochemical staining was performed for nerve growth factor (NGF), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and smooth muscle α-actin. Results CNCI significantly decreased erectile function at 12 weeks (51.7% vs. 71.9%, mean ICP/BP ratio, p<0.05) and increased the expression of HIF-1α and decreased the expression of eNOS, nNOS, and SHH. At 24 weeks, erectile function in the CNCI group was improved with no significant difference versus the sham group (70.5% vs. 63.3%, mean ICP/BP ratio, p<0.05) or the CN group at 12 weeks (51.7% vs. 63.3%, mean ICP/BP ratio, p<0.05). By RT-PCR, the increase in HIF-1α and decrease in SHH mRNA was restored at 24 weeks. By immunohistochemistry, the expression of eNOS and nNOS was increased at 24 weeks. Conclusions CN injury induces significantly impaired erectile function and altered gene and protein expression, which suggests that local hypoxic and inflammatory processes may contribute to this change. Significant spontaneous recovery of erectile function was observed at 6 months after CN crush injury.

Effect of improvement in lower urinary tract symptoms on sexual function in men: Tamsulosin monotherapy vs. combination therapy of tamsulosin and solifenacin

Purpose To evaluate how much the improvement of lower urinary tract symptoms (LUTS) affects sexual function and which storage symptoms or voiding symptoms have the greatest effect on sexual function. Materials and Methods A total of 187 patients were enrolled in this study. Patients were randomly assigned to receive either tamsulosin 0.2 mg (group A) or tamsulosin 0.2 mg and solifenacin 5 mg (group B). At 4 weeks and 12 weeks, the LUTS and sexual function of the patients were evaluated by use of the International Index of Erectile Function-5 (IIEF5), International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS) questionnaire, uroflowmetry, and bladder scan. Results Both groups A and B showed statistically significant improvements in IPSS, OABSS, and quality of life (QoL). Group A showed improved maximum flow rate, mean flow rate, and residual urine volume by time. Group B did not show an improvement in flow rate or residual urine volume but total voiding volume increased with time. The IIEF5 score was not improved in either group. In group A, the IIEF5 score dropped from 13.66±4.97 to 11.93±6.14 after 12 weeks (p=0.072). Group B showed a decline in the IIEF5 score from 13.19±5.91 to 12.45±6.38 (p=0.299). Although group B showed a relatively smaller decrease in the IIEF5 score, the difference between the two groups was not significant (p=0.696). Conclusions Tamsulosin monotherapy and combination therapy with solifenacin did not improve erectile function despite improvements in voiding symptoms and QoL. The improvement in storage symptoms did not affect erectile function.

Urologist's Practice Patterns Including Surgical Treatment in the Management of Premature Ejaculation: A Korean Nationwide Survey.

Purpose According to previous studies, the prevalence of premature ejaculation (PE) in Korea ranges from 11.3% to 33%. However, the actual practice patterns in managing patients with PE is not well known. In this study, we have endeavored to determine how contemporary urologists in Korea manage patients with PE. Materials and Methods The e-mailing list was obtained from the Korean Urological Association Registry of Physicians. A specifically designed questionnaire was e-mailed to the 2,421 urologists in Korea from May 2012 to August 2012. Results Urologists in Korea diagnosed PE using various criteria: the definition of the International Society for Sexual Medicine (63.4%), Diagnostic and Statistical Manual of Mental Disorders (43.8%), International Statistical Classification of Disease, 10th edition (61.7%), or perceptional self-diagnosis by the patient himself (23.5%). A brief self-administered questionnaire, the Premature Ejaculation Diagnostic Tool, was used by only 42.5% of the urologists. Selective-serotonin reuptake inhibitor (SSRI) therapy was the main treatment modality (91.5%) for PE patients. 40.2% of the urologists used phosphodiesterase type 5 inhibitors, 47.6% behavior therapy, and 53.7% local anesthetics. Further, 286 (54.3%) urologists managed PE patients with a surgical modality such as selective dorsal neurotomy (SDN). Conclusions A majority of Korean urologists diagnose PE by a multidimensional approach using various diagnostic tools. Most urologists believe that medical treatment with an SSRI is effective in the management of PE. At the same time, surgical treatment such as SDN also investigated as one of major treatment modality despite the lack of scientific evidence.

Efficacy and safety of the simultaneous administration of mirodenafil and an α-blocker in men with BPH-LUTS: a multicenter open-label prospective study.

We evaluated the clinical efficacy and safety of the coadministration of a PDE5 inhibitor and an α-adrenergic blocker in patients with both benign prostatic hyperplasia/lower urinary tract symptoms (BPH-LUTS) and ED using mirodenafil 50 mg (Mvixx) once daily (OD) in patients already receiving stable α-blocker therapy. This study was a prospective, multicenter, open-label trial. We selected 147 patients undergoing stable (longer than 4 weeks) α-blocker therapy for BPH-LUTS as recipients of the additive mirodenafil 50 mg OD for 8 weeks. The coprimary measures were the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5). The key secondary measures were peak flow rate (Qmax) and postvoiding residual (PVR) volume. Safety was assessed by evaluating cardiovascular parameters and the participant-reported treatment-emergent adverse events (TEAEs). The additional administration of mirodenafil 50 mg OD significantly improved IPSS results (18.70–14.30 at 4 weeks and 18.70–13.72 at 8 weeks; P<0.001). The IIEF-5 score was improved at 8 weeks (10.94–16.16; P<0.001). There was no significant change in systolic blood pressure/diastolic blood pressure (124.8 mm Hg/78.6 mm Hg–122.0 mm Hg/79.6 mm Hg; P=0.638) and heart rates (78.8 per min to 80.2 per min; P=0.452). The most common TEAEs were hot flashes (10.9%) and headache (8.1%). The combination of mirodenafil with an α-blocker did not significantly improve PVR; however, Qmax was improved at 8 weeks (14.51–16.80 ml s−1; P=0.026). Mirodenafil 50 mg OD in combination with an α-blocker appeared to have few adverse effects, to improve BPH-LUTS and restore sexual function.

Tolerability and efficacy of newly developed penile injection of cross-linked dextran and polymethylmethacrylate mixture on penile enhancement: 6 months follow-up

Cross-linked dextran and polymethylmethacrylate mixture (Lipen-10) is newly developed tissue filler. The purpose of this study was to evaluate tolerability and efficacy of Lipen-10 on penile enhancement. Twenty adult males were included in this study. Lipen-10 was injected into the subcutaneous tissue of the penile shaft. The penile girth and length were measured in the flaccid state, before and 1, 3 and 6 months after the injection. The circumference increased by 3.7±1.2 cm (50.8%, P<0.0001) at penile base, 4.2±0.9 cm (59.0%, P<0.001) at mid-shaft, and 3.8±1.0 cm (53.2%, P<0.0001) at distal shaft and the length increased by 2.3±1.4 cm (63.2%, P<0.001). There was, however, no significant difference between 3 and 6 months post-treatment in girth and length (P-values: 0.796, 0.498, 0.600 and 0.084 for penile base, mid- and distal-shaft and length, respectively). The complications were only one mild asymmetry of penile shape and one 5-mm-sized nodule in the injected site. There were no clinically significant adverse events in all subjects. Penile injection of Lipen-10 led to a significant increase in penile size, showed a good durability and was well-tolerated, without serious adverse events. These results suggest that penile injection of Lipen-10 may be a new effective method for penile enhancement.