Jae Seung Paick

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: Efficacy and Safety of Mirodenafil, A New Oral Phosphodiesterase Type 5 Inhibitor, for Treatment of Erectile Dysfunction

INTRODUCTIONnMirodenafil is a newly developed oral phosphodiesterase type 5 inhibitor, currently under investigation as a treatment for erectile dysfunction (ED).nnnAIMnWe 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.nnnMETHODSnA 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.nnnMAIN OUTCOME MEASURESnPrimary 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.nnnRESULTSnMirodenafil 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.nnnCONCLUSIONSnMirodenafil, 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.

The Efficacy and Safety of Udenafil, a New Selective Phosphodiesterase Type 5 Inhibitor, in Patients with Erectile Dysfunction

INTRODUCTIONnUdenafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for the treatment of erectile dysfunction (ED).nnnAIMnThis study was performed to evaluate the efficacy and safety of udenafil therapy in patients with ED.nnnMETHODSnIn this multicenter, double-blind, placebo-controlled, fixed-dose, parallel-group phase III trial, 167 patients with ED of diverse origin and severity were randomized to take placebo or udenafil at fixed doses of 100 or 200 mg as needed for 12 weeks.nnnMAIN OUTCOME MEASURESnPrimary efficacy variable was change from baseline in erectile function (EF) domain scores of the International Index of Erectile Dysfunction (IIEF) questionnaire. Secondary efficacy variables include change from baseline in scores on the IIEF Questions 3 and 4 (IIEF Q3 and Q4), change from baseline in all domain scores of the IIEF, patients responses to questions 2 and 3 of the Sexual Encounter Profile (SEP2 and SEP3), and patients responses to the Global Assessment Question (GAQ). Any adverse events were also recorded during the trial.nnnRESULTSnAfter 12 weeks of treatment, the patients treated with udenafil showed significantly greater change from baseline in the IIEF-EF domain score compared with placebo (placebo, 0.20; 100-mg udenafil, 7.52; and 200-mg udenafil, 9.93, respectively) (P < 0.0001). Compared with placebo, udenafil significantly enhanced the rates of successful penetration (SEP Q2) and maintenance of erection (SEP Q3) (P < 0.0001). Furthermore, significantly greater proportions of udenafil treatment groups responded positively to the GAQ compared with the placebo group (GAQ: placebo, 25.9%; 100-mg udenafil, 81.5%; and 200-mg udenafil, 88.5%, respectively) (P < 0.0001). Treatment-related adverse events were generally mild to moderate with facial flushing and headache being the most common.nnnCONCLUSIONSnUdenafil is an effective and well-tolerated therapy for ED of broad-spectrum etiology and severity.

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

BACKGROUNDnA 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.nnnOBJECTIVEnTo evaluate the efficacy and safety of once-daily dosing of udenafil in the treatment of ED.nnnDESIGN, SETTING, AND PARTICIPANTSnThis 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.nnnMEASUREMENTSnThe 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.nnnRESULTS AND LIMITATIONSnCompared 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.nnnCONCLUSIONSnUdenafil 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.

The Efficacy and Safety of Testosterone Undecanoate (Nebido®) in Testosterone Deficiency Syndrome in Korean: A Multicenter Prospective Study

INTRODUCTIONnLong-acting injectable testosterone undecanoate (TU, Nebido(®)), a new parenteral testosterone preparation, has recently been introduced to avoid frequent injections of the conventional injectable esters.nnnAIMSnTo assess the efficacy and safety of long-acting injectable testosterone undecanoate (TU, Nebido(®)) in Korean patients with testosterone deficiency syndrome (TDS).nnnMETHODSnOne hundred thirty-three patients who complain of erectile dysfunction with serum testosterone level less than 3.5 ng/mL were injected with 1,000 mg of TU (4 mL/ample) on day 1, followed by another injection after 6 weeks and 18 weeks. For the safety profiles, serum hemoglobin (Hb), hematocrit (Hct), glucose, lipid profile, and prostate-specific antigen (PSA) were measured.nnnMAIN OUTCOME MEASURESnBody mass index (BMI) was measured at the time of the first visit and after 12, 24 weeks. Primary efficacy was evaluated according to changes in the International Index of Erectile Function (IIEF) from the initial visit to the final visit (24 weeks) and from the initial visit to each visit. Secondary efficacy was assessed with changes of the Aging Males Symptoms (AMS) Scale and the Global Efficacy Question (GEQ) for improvement of erectile function.nnnRESULTSnMean age of patients was 54 ± 9.6 years. Compared with pretreatment, no significant improvement in BMI was observed. Serum total testosterone and free testosterone were significantly increased at 12 weeks and were maintained until 24 weeks (P < 0.001). TU significantly decreased cholesterol (P < 0.0001). TU significantly improved total IIEF, all five domain scores of IIEF (P < 0.0001) and total AMS, all three domain scores of AMS (P < 0.0001). On GEQ, TU improved erectile function in 76.9% of subjects. On safety profile, TU significantly elevated Hb, Hct, and PSA at 24 weeks but within normal range. No serious adverse reactions were observed. Drop-out rate was 15.0%.nnnCONCLUSIONSnIn this prospective multicenter study, TU was effective, safe, and tolerable until 24 weeks in Korean TDS patients. Further well-controlled, long-term study should follow.

Prevalence of urinary incontinence in Korean women:an epidemiologic survey

The purpose of this study was to evaluate the prevalence of urinary incontinence (UI) in a Korean national community sample of female adults aged 30–79xa0years. During April 2003, a national Korea telephone survey using quota sampling methods was conducted. The clinically validated computer-assisted telephone interview approach was used in the survey. Of the 1,500 subjects contacted, 1,303 were successfully interviewed (response rate 86.9%). Overall, UI was reported by 40.8%, and 22.9, 3.1, and 14.9% reported pure stress, urge, and mixed UI, respectively. The prevalence of stress, urge, and mixed UI generally did not increase with age. Urge and mixed UI had a greater impact than stress UI on daily tasks (Pu2009<u20090.001), social life (Pu2009<u20090.001), depression or anxiety due to UI (Pu2009<u20090.001), worry about UI (Pu2009<u20090.001), sex life (Pu2009<u20090.001), wear protection due to UI (Pu2009=u20090.011), and quality of life (Pu2009<u20090.001). In subjects with pure stress UI, 28.3% reported impaired quality of life compared with 43.9% and 43.8% of subjects with urge and mixed UI. Of those individuals with stress, urge, and mixed UI, 19.1, 20.0, and 25.8% had the willingness to seek medical consultation. This study is the first to examine the prevalence of UI in Korean women. The present study revealed that there was a high prevalence of UI in this population. Our descriptive research provides a valuable insight into the need for tailored education to this population about UI.

Doppler sonography of deep cavernosal artery of the penis: variation of peak systolic velocity according to sampling location.

To determine if there are significant variations in the peak systolic velocity of cavernosal arteries according to the Doppler sampling location, Doppler sonography was performed in 32 patients with erectile dysfunction and 15 control patients. Doppler spectral waveforms were obtained at proximal and distal locations in cavernosal artery. The peak systolic velocity of the cavernosal artery was 39.0 +/‐ 11.2 cm/sec in proximal portion and 20.0 +/‐ 5.6 cm/sec in distal portion in patients with erectile dysfunction. In control patients, the peak systolic velocity was 39.8 +/‐ 8.0 cm/sec in proximal portion and 21.3 +/‐ 5.5 cm/sec in distal portion. The peak systolic velocity of the cavernosal artery varies significantly according to the sampling location in patients with erectile dysfunction as well as in control patients. Our study demonstrated that the sampling location needs to be standardized in performing Doppler sonography of the cavernosal arteries, and we propose the proximal cavernosal artery where it angles posteriorly as the standardized sampling location.

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

Study Type – Therapy (RCT)

The Learning Curve for Holmium Laser Enucleation of the Prostate: A Single-Center Experience

PURPOSEnHolmium laser enucleation of the prostate (HoLEP) is known to have a steep learning curve and, as a result, its clinical usage has limitations. The purpose of this study was to analyze the learning curve and early complications following the HoLEP procedure.nnnMATERIALS AND METHODSnA retrospective analysis was performed on 161 patients who had undergone the HoLEP procedure for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH) from July 2008 to September 2009. The procedure was done by two surgeons. Perioperatively, enucleated tissue weight, enucleation time, morcellation time, enucleation ratio (enucleation weight/transitional zone volume), and enucleation efficiency (enucleated weight/enucleation time) were analyzed, and early complications were assessed.nnnRESULTSnMean enucleation time, morcellation time, and enucleation ratio were 61.3 min (range, 10-180 min), 12.3 min (range, 2-60 min), and 0.66 (range, 0.07-2.51), respectively. In terms of efficiency, enucleation efficiency was 0.32 g/min (range, 0.02-1.25 g/min) and morcellation efficiency was 1.73 g/min (range, 0.1-7.7 g/min). Concerning the learning curve, enucleation efficiency was stationary after 30 cases (p<0.001), morcellation efficiency reached a learning curve at 20 cases (p=0.032), and enucleation ratio had no learning curve in this study. There were several cases of surgery-related complications, including bladder mucosal injury by the morcellator (13%), capsular injury during enucleation (7%), and conversion to a conventional resectoscopy procedure (15%), which showed a reduction in incidence with time.nnnCONCLUSIONSnThe learning curve of HoLEP is steep; however, it can be overcome gradually. Further study is necessary with respect to long-term postoperative follow-up.

Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo-Controlled Pilot Study Using Tamsulosin as an Active Control

Objectives: Assess the efficacy and safety of once‐daily tadalafil or tamsulosin versus placebo during 12 weeks on lower urinary tract symptoms (LUTS) in Korean men with benign prostatic hyperplasia (BPH).

Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double- blind, placebo-controlled, fixed dose, parallel group clinical trial

AIMnTo evaluate the efficacy and safety of SK3530, a newly developed type 5 phosphodiesterase inhibitor (PDE5I), in Korean men with erectile dysfunction (ED).nnnMETHODSnA total of 119 patients were randomized at 10 centers in Korea to receive either SK3530 (50, 100, or 150 mg; n = 89) or placebo (n = 30) taken l h before anticipated sexual activity for an 8-week period. The patients were evaluated at baseline and 4 and 8 weeks after beginning therapy. Efficacy was assessed using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and the Global Assessment Question (GAQ). Safety was analyzed by adverse events, laboratory values and vital signs.nnnRESULTSnAt the end of the study, all the primary and secondary efficacy end-points were statistically significantly improved by SK3530 compared with placebo (P<0.05). Of the 89 patients in the treatment arm, 36 (42.3%) achieved normal erectile function after treatment, including six patients with severe ED. Treatment-related adverse events occurred in 32 patients. The most common adverse events were flushing, headache, dizziness and eye redness (10.9%, 7.6%, 2.5% and 2.5%, respectively), and most were mild. Only two patients discontinued treatment during the study period because of adverse events.nnnCONCLUSIONnThe results of our phase II study have confirmed the efficacy and safety of SK3530 in a broad population of men with ED of various etiologies and severity. The optimal doses in terms of efficacy and safety were determined to be 50 mg and 100 mg, respectively.