Safety and efficacy of vardenafil in patients with erectile dysfunction: Result of a bridging study in Japan

AIM: Vardenafil is a selective and highly potent phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), with improved selectivity for PDE5 and demonstrated efficacy for improving sexual function in men with ED. The current study investigated the safety and efficacy of this new PDE5 inhibitor in Japanese men with ED. METHODS: This was a prospective, double blind, randomized clinical trial designed to evaluate the efficacy and safety of vardenafil. Following a 4-week treatment-free observation period, 283 eligible patients were randomized to 12 weeks treatment with vardenafil 5 mg, 10 mg, 20 mg, or placebo. Primary efficacy responses were assessed using the scores of Q3 and Q4 of the international index of erectile function (IIEF). RESULTS: All three vardenafil doses showed significantly better improvement than the placebo group in Q3 and Q4 scores of the IIEF questionnaire, either at 12 weeks or at the 'last observation carried forward' (LOCF, P < 0.0001). Q3 scores were improved to 4.06 with vardenafil 5 mg, 4.53 with vardenafil 10 mg, and 4.64 with vardenafil 20 mg, versus 3.17 with placebo. Comparable scores for Q4 were 3.47, 4.15 and 4.31 versus 2.31 for placebo. Up to 86% of patients achieved improved erections as assessed by the global assessment question (GAQ). Reported adverse event rates were 35.3%, 45.3% and 54.5% with vardenafil 5 mg, 10 mg and 20 mg, respectively, versus 21.1% in the placebo group. No serious adverse drug reactions were reported. The most common treatment-emergent adverse events were transient headache, flushing and rhinitis, which were mostly mild. CONCLUSION: Vardenafil is an effective and well-tolerated treatment for ED and provides improvement in key indices of erectile function among Japanese men with ED. The results of our trial show that up to nearly 90% of patients achieve improved erections with the administration of vardenafil.     

伐地那非治疗勃起功能障碍的多中心、随机、双盲、对照研究

目的　观察伐地那非治疗勃起功能障碍的安全性和有效性。　方法　采用多中心、随机、双盲、安慰剂对照的方法 ,在国内 7家中心对 6 2 4例勃起功能障碍者口服伐地那非的勃起功能改善情况进行临床观察。患者随机按 1∶1∶1∶1进入安慰剂组及伐地那非 5、10、2 0mg组 ,每组各 15 6例 ,完成 4周洗脱期和 12周治疗期。患者按需在性交前 1h服用 1片研究药物。每日最多服用 1次研究药物。观察治疗 12周后国际勃起功能指数 (IIEF)问卷中有关勃起功能部分 (问题 1～ 5和 15 )的得分 ,患者日记中有关插入的成功率及成功保持勃起的成功率。　结果　共有 6 0 2例 (96 .5 % )进入安全性评估和意向性分析 ,各组分别为安慰剂组 14 8例 (94 .9% )、5mg组 15 1例 (96 .8% )、10mg组 15 0例 (96 .2 % )、2 0mg组 15 3例 (98.1% )。完全符合方案人群共 4 6 8例 (75 .0 % ) ,各组分别为 :安慰剂组 12 0例 (76 .9% )、5mg组 118例 (75 .6 % )、10mg组 10 6例 (6 8.0 % )、2 0mg组 12 4例 (79.5 % )。意向性分析人群的IIEF勃起功能部分 (问题 1～ 5 ,15 )得分的统计结果 ,用药 12周后 ,伐地那非 5mg组、10mg组和 2 0mg组的平均得分基线分别为 13.3分、14 .1分和 13.6分 ,分别增加到 2 2 .2分、2 2 .8分和 2 3.6分 ,与安慰剂组     

The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial

Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.     

Comparison of the efficacy and safety of once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction

We compared the efficacy and safety between once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction (ED). A multi-center, randomized, open-label, parallel-group, 12-week study was conducted. 161 patients who improved with on-demand 200 mg of udenafil according to Sexual Encounter Profile (SEP) diary Question 2 and 3 (Q2 and Q3) were randomized into 200 mg on-demand (n = 80) or 50 mg once-daily (n = 81) dosing groups for 8 weeks. The dosing period was followed by a 4-week treatment-free period. The primary efficacy endpoint was the change of the International Index of Erectile Function (IIEF) erectile function domain (EFD) score. The secondary efficacy endpoints included changes to the SEP diary Q2, Q3, IIEF Q3, Q4, other domains of IIEF, Global Assessment Question, and shift to the normal rate (EFD ≥ 26). Vascular endothelial markers were also assessed. The IIEF-EFD score of both groups improved after 8 weeks of treatment (P < 0.0001). There was no statistically significant difference between two groups. Improvement was not maintained after the treatment-free follow-up period. Similar results were observed in the secondary efficacy endpoints. There was also no significant difference in vascular endothelial markers. Daily udenafil was well-tolerated, and there was no significant difference in the adverse drug reactions and adverse events between the two groups. Flushing and headache were the most frequent adverse events. Both regimens improved ED in diabetic patients and were well-tolerated. Further studies are needed to assess the effect of daily udenafil treatment in diabetic patients.     

Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies

OBJECTIVES: To determine the efficacy and safety of fixed-dose oral sildenafil in patients with erectile dysfunction (ED) of various etiologies. METHODS: In a 12-week, double-blind, randomized, placebo-controlled, fixed-dose study, 514 men (mean age 56 years) with ED were randomized to receive 25, 50, or 100 mg of sildenafil or placebo. The primary etiology of ED was determined to be organic in 32% of men, psychogenic in 25%, or mixed in 43%. Sildenafil or placebo was taken in the home setting approximately 1 hour before sexual activity, not more than once daily. Efficacy was determined by responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) of the 15-item International Index of Erectile Function (IIEF). Other measures of efficacy included the five sexual function domains of the IIEF, a global efficacy question, event log data, and a partner questionnaire. RESULTS: Sildenafil significantly increased patients' ability to achieve and maintain erections (P <0.0001), with efficacy increasing with increasing dose. Significant improvements were also observed in the IIEF domains for erectile function, orgasmic function, intercourse satisfaction, and overall sexual satisfaction (P <0.0001). The proportion of subjects who felt that treatment with sildenafil improved their erections was significantly greater (67% to 86%) than that with placebo treatment (24%, P <0.0001). The proportion of successful attempts at sexual intercourse also increased significantly with sildenafil treatment (P <0.001). Partner responses corroborated patient reports. Sildenafil was well tolerated at the three doses studied. CONCLUSIONS: Oral sildenafil is an effective, well-tolerated treatment for ED of various etiologies.     

Efficacy and safety of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in Egypt and South Africa

The efficacy of sildenafil citrate (Viagra), an oral agent for the treatment of erectile dysfunction (ED), has been demonstrated in global studies. This 12-week randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study assessed the efficacy and safety of sildenafil to treat ED in men in Egypt and South Africa. Men with ED of varied etiology were randomized to receive sildenafil 50 mg (n=128) or placebo (n=126); doses could be adjusted to 100 or 25 mg. Questions from the International Index of Erectile Function (IIEF) assessing the ability to achieve (Q3) and maintain (Q4) erections demonstrated a significant improvement with sildenafil compared with placebo (P<0.0001). Improved erections were reported by 74% of patients receiving sildenafil and 27% of those receiving placebo (P<0.0001). Headache, dyspepsia, and flushing were the most common adverse events in sildenafil-treated patients. These results are consistent with clinical trials in other countries. We conclude that sildenafil is an efficacious and well-tolerated treatment for men with ED in Egypt and South Africa.     

A dose-escalation study to assess the efficacy and safety of sildenafil citrate in men with erectile dysfunction

OBJECTIVE: To assess the efficacy and safety of sildenafil citrate (Viagra, Pfizer Inc., USA) in a double-blind, placebo-controlled, dose-escalation study over a period of 26 weeks in men with erectile dysfunction of a broad spectrum of aetiology. PATIENTS AND METHODS: In all, 315 patients from five countries were randomized to receive treatment with placebo (156 men) or sildenafil (159 men). Significant concomitant medical conditions were hypertension (20%), a history of pelvic surgery (19%), diabetes mellitus (15%), and ischaemic heart disease (10%). Patients randomized to treatment received a starting dose of 25 mg of sildenafil or matching placebo, which could be increased to 50 mg and then to 100 mg of sildenafil, based on efficacy and tolerability. Assessments of efficacy comprised the 15-item International Index of Erectile Function (IIEF), including question three (ability to achieve an erection) and question four (ability to maintain an erection), a partner questionnaire, an overall efficacy question, and event-log data. RESULTS: After 12 weeks of treatment, 26%, 32% and 42% of patients were taking 25, 50 and 100 mg of sildenafil, respectively. A similar distribution of doses was reported after 26 weeks of treatment. Treatment with sildenafil significantly improved the patients' abilities to achieve and maintain an erection compared with treatment with placebo (P < 0.001). Scores for four of the five sexual function domains of the IIEF (erectile function, orgasmic function, intercourse satisfaction and overall satisfaction) also improved significantly (P < 0.001). There was a significant improvement in the mean score for the erectile function domain, regardless of the aetiology of erectile dysfunction (P < 0.001). After 12 weeks and 26 weeks of treatment, 82% and 79% of patients receiving sildenafil reported improved erections, compared with 24% and 23% of patients receiving placebo, respectively (P < 0.001). Treatment-related adverse events were mild to moderate and occurred in 27% of patients receiving sildenafil, compared with 8% of patients receiving placebo. CONCLUSION: Sildenafil is an effective and well-tolerated treatment for men with erectile dysfunction of a broad spectrum of aetiology.     

Efficacy and treatment satisfaction with on-demand tadalafil (Cialis) in men with erectile dysfunction

OBJECTIVE: Tadalafil (Cialis) is an inhibitor of phosphodiesterase type 5, which mediates relaxation of vascular smooth muscle in the corpus cavernosum thus facilitating erection. The purpose of this multicentre, randomized, double-blind, parallel group, placebo-controlled study was to evaluate efficacy and treatment satisfaction of on-demand Cialis in men with mild-to-severe erectile dysfunction (ED). METHODS: Following a 4-week treatment-free run in period, patients stratified into three severity groups by the International Index of Erectile Function (IIEF) Erectile Function (EF) domain score were randomized to receive either placebo or Cialis 20 mg taken on demand over a 12-week period. Efficacy endpoints were change from baseline in IIEF EF domain scores, responses to Sexual Encounter Profile diary (SEP) questions, and responses to the Global Assessment Questions (GAQ). Treatment satisfaction was evaluated using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire in two of seven participating countries where validated translations were available. RESULTS: Of the 443 men who entered the trial, 409 (mean age, 52 years) formed the intent-to-treat population. Mean baseline demographics and ED severity measures were balanced between treatment groups except for a higher percentage of patients na?ve to sildenafil in the tadalafil group compared to placebo (50% versus 36%). The percentage of patients in each IIEF EF severity class (mild, moderate and severe) was 47%, 30% and 23% for placebo patients and 48%, 29% and 23% for tadalafil patients, respectively. Tadalafil was significantly superior to placebo on all primary efficacy measures (IIEF EF domain scores, SEP15, GAQ1; p < 0.001); notably 64% of tadalafil patients achieved a normal IIEF EF domain score at endpoint compared to 16% of placebo patients (p < 0.001). Of the 185 patients completing the EDITS questionnaire (137 receiving Cialis and 48 receiving placebo), tadalafil-treated patients had a median EDITS score of 84 (95%CI 80, 86), which was significantly higher than the median score for placebo-treated patients of 41 (95%CI 32, 59; p < 0.001; Wilcoxon test). The proportion of patients satisfied with treatment (defined as final EDITS score greater than 50) was 87% for the tadalafil-treated group and 46% for the placebo-treated group (p < 0.001; exact test). Adverse events were significantly more common with tadalafil than placebo (p < 0.01) and included primarily headache (7.2% versus 1.9%) and flushing (4.6% versus 0%). One patient discontinued tadalafil treatment due to back pain. CONCLUSION: In men with mild-to-severe ED, tadalafil 20 mg significantly improves erectile function, demonstrates superior treatment satisfaction relative to placebo, and is well tolerated. This is the first study to yield efficacy data on tadalafil in an Eastern European population of men with erectile dysfunction, and the first to measure satisfaction with the EDITS questionnaire in any study population of men with this condition using tadalafil.     

Efficacy and safety of on-demand tadalafil for the treatment of erectile dysfunction in South-East Asian men

AIM: Tadalafil is an inhibitor of phosphodiesterase type 5 used for the treatment of erectile dysfunction (ED). The efficacy and safety of tadalafil have been evaluated extensively in Western populations. Our aim was to assess the efficacy and safety of on-demand tadalafil for the treatment of ED in South-East Asian men. METHODS: This was a randomized, double-blind, placebo-controlled study of men with mild to severe ED of various etiologies randomized to receive placebo (n = 122), tadalafil 10 mg (n = 120), or tadalafil 20 mg (n = 125), taken as needed (maximum once daily) for 12 weeks. Efficacy assessments included the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). RESULTS: Men from China, Singapore, and the Philippines participated in this trial (n = 367). Compared with placebo, tadalafil significantly improved erectile dysfunction on all efficacy outcomes (P < 0.001). Patients receiving tadalafil 10 mg and 20 mg experienced a significant mean improvement of 8.1 and 8.7, respectively, in the IIEF Erectile Function (IIEF-EF) domain score from baseline (vs placebo 2.4, P < 0.001). In patients receiving tadalafil 10 mg and 20 mg, the mean per-patient success rate for intercourse attempts (SEP3) was 62% and 70%, respectively, compared with 32% for the placebo group (P < 0.001). Of patients who received tadalafil 10 mg and 20 mg, 81% and 86% reported improved erections at endpoint (GAQ) compared with 44% in the placebo group (P < 0.001). The most common adverse events reported by patients were headache, back pain, dyspepsia, and dizziness. CONCLUSIONS: Tadalafil was an effective and well-tolerated treatment for South-East Asian men with ED.     

Efficacy, tolerability and satisfaction with sildenafil citrate 100-mg titration compared with continued 50-mg dose treatment in men with erectile dysfunction

OBJECTIVE

To evaluate the efficacy, tolerability, and treatment satisfaction after initiating treatment with sildenafil 50 mg and later titrating to 100 mg, compared with continuing treatment with sildenafil 50 mg, in men with erectile dysfunction (ED).

PATIENTS AND METHODS

A multicentre, parallel‐group trial was conducted in two 4‐week periods. In period 1, patients received 50‐mg doses of sildenafil single‐blinded for 4 weeks. In period 2, patients were randomized to double‐blind, placebo‐controlled treatment with sildenafil 50 mg or sildenafil 100 mg for 4 weeks. All patients were aged ≥18 years with a documented clinical diagnosis of ED (score of ≤25 on the International Index of Erectile Function, IIEF, Erectile Function, EF, domain), and met the prescribing criteria for sildenafil 50 mg and 100 mg.

RESULTS

Of 492 enrolled patients (mean age 53 years, sd 11), 476 (97%) completed period 1 and 473 (96%) completed period 2. Patients receiving sildenafil 50 mg in period 1 had an increase in the mean (sd ) baseline EF domain score from 12.8 (5.2) to 22.5 (6.6) (P < 0.001), and improved scores on the Quality of Erection Questionnaire (QEQ) and Sexual Experience Questionnaire (SEX‐Q). The IIEF EF domain scores were similar in the two groups at baseline and randomization. Patients titrated to the 100‐mg dose (237 men) showed a significantly greater improvement than those who continued on the 50‐mg dose (240; P < 0.001). There was a significant increase in QEQ and SEX‐Q scores in patients titrated to sildenafil 100 mg compared with patients continuing at sildenafil 50 mg. At either sildenafil dose, headache, flushing and hot flushes were the most common adverse events. Neither the frequency nor the severity of adverse events increased with titration to sildenafil 100 mg.

CONCLUSIONS

After initial treatment with sildenafil 50 mg, patients titrated to 100 mg showed further increases in efficacy and satisfaction with no increase in the number or severity of adverse events than in those remaining on the starting dose.     

酚妥拉明治疗勃起功能障碍安全性和有效性的多中心评价

目的 :评价甲磺酸酚妥拉明胶囊 (MP)治疗男性勃起功能障碍 (ED)的安全性和有效性。　方法 :采用随机、双盲、安慰剂对照多中心临床试验 ,入选 168例病人 ,分别服用试验药物MP和安慰剂 ,4 0mg/次。观察服药后国际勃起功能指数 (IIEF)得分变化及夜间记录表。　结果 :试验组IIEF观察表中Q3、Q4及Q3+Q4得分增加明显高于对照组 (P <0 .0 0 1) ,试验组治疗ED显效率 10 .12 %、有效率 67.4 2 % ,对照组显效率 0 ,有效率 14 .2 9% (P均 <0 .0 1) ;试验组不良反应率 4 .76% ,对照组为 1.19% (P >0 .0 5 ) ,不良反应均不需特殊处置。　结论 :MP治疗ED安全、有效。     

Clinical efficacy of Apomorphine SL in erectile dysfunction of diabetic men

Although subgroup analyses from large randomised premarketing studies have shown that Apomorphine SL enhances the percentage of erections firm enough for sexual intercourse in diabetic men, the clinical role of the drug in this patient population remains to be elucidated. The aim of the present study was to assess the efficacy of Apomorphine SL in diabetic males with erectile dysfunction (ED) and to identify factors predicting those who may benefit from the treatment. A total of 130 diabetic patients were randomised to receive either four tablets of 3 mg Apomorphine or a matching placebo. Assessments of efficacy comprised the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and the one-item global efficacy question (GEQ). Patients with both a positive response to the GEQ and an improvement of at least 5 points in the EF domain of the IIEF were considered responders and subanalysed by several parameters indicative of the severity of both ED and diabetes. Response rate was 17% after placebo and 22% after Apomorphine SL. The EF domain of the IIEF and both questions 3 and 4 scores did not significantly improve in either of the two arms over the baseline. A younger age and a lower Hb1Ac were significantly linked to the status of responder in the Apomorphine arm. Apomorphine SL failed to show a statistically significant benefit over a placebo, but 22% of patients had a clinically significant erectile response. These figures seem to suggest that the drug has a limited use for ED diabetic patients.     

西地那非治疗勃起功能障碍的有效性:中文文献的meta分析

目的评价西地那非治疗ED的有效性。方法通过中国生物医学文摘光盘(CBMdisc 2004新版)和清华同方数据库中CHKD期刊全文库检索公开发表的中文文献。凡摘要或方法中出现随机对照字样,无论有无盲法均予纳入。对纳入的试验设计特征用Jadad计分评价。以IIEF中Q3和Q4评分及IIEF总评分为疗效指标,采用RevMan4．1软件进行Meta分析。结果共有9个随机对照试验被纳入。其中6个为Jadad计分3分以上高质量试验。5个试验的IIEF Q3和Q4评分meta分析,OR=8．83,95％CI为(6．67,11．69),P<0．0001。4个高质量试验的IIEF总评分meta分析OR=13．76,95％CI为(9．50,19．92),P<0．0001。显示西地那非能够显著提高ED患者的疗效指标。结论西地那非能有效改善男性勃起功能,是一种有效治疗ED的口服药物。     

Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone

PURPOSE: We compare the efficacy of testosterone gel (T-gel) versus placebo as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. MATERIALS AND METHODS: A randomized, placebo controlled, double-blind, parallel group, multicenter study was performed. A total of 75 hypogonadal men (18 to 80 years old, morning serum total testosterone 400 ng/dl or less) with confirmed lack of response to sildenafil monotherapy were randomized (1:1) to receive a daily dose of 1% T-gel or 5 gm placebo gel as adjunctive therapy to 100 mg sildenafil during a 12-week period. Subjects were evaluated for sexual function, primarily based on the International Index of Erectile Function (IIEF), quality of life and serum testosterone levels at baseline and weeks 4, 8 and 12. RESULTS: Testosterone treated subjects had greater improvement in erectile function compared to those who received placebo, reaching statistical significance at week 4 (4.4 vs 2.1, p = 0.029, 95.1% CI 0.3, 4.7). Similar trends were observed for improvements in orgasmic function, overall satisfaction, total IIEF score and percentage of IIEF responders. T-gel significantly (p < or =0.004) increased total and free testosterone levels throughout the study, although no significant correlations were made between testosterone levels and the IIEF at end point. CONCLUSIONS: T-gel taken with sildenafil may be beneficial in improving erectile function in hypogonadal men with erectile dysfunction who are unresponsive to sildenafil alone.     

Vardenafil improved patient satisfaction with erectile hardness, orgasmic function and sexual experience in men with erectile dysfunction following nerve sparing radical prostatectomy

PURPOSE: Nerve sparing radical retropubic prostatectomy (NS-RRP) results in erectile dysfunction in a significant number of patients. Vardenafil, a potent and selective phosphodiesterase type 5 inhibitor, is generally safe. It improves International Index of Erectile Function erectile function domain scores, and penetration and erection maintenance success rates in patients who have undergone NS-RRP. We report additional parameters important to patient perceptions regarding erection quality and satisfaction with sexual experience following NS-RRP. MATERIALS AND METHODS: A total of 440 men at 58 centers throughout the United States and Canada participated in this randomized, placebo controlled, double-blind trial with 3 phases, namely baseline (4-week untreated period), treatment (12 weeks) and followup (7 days). Participants received placebo (145), 10 mg vardenafil (146) or 20 mg vardenafil (149) at home on demand but no more than once per calendar day. Efficacy and satisfaction with erection quality and sexual experience were determined during the trial. RESULTS: The 10 and 20 mg vardenafil doses were significantly superior to placebo for the International Index of Erectile Function domains for intercourse satisfaction, orgasmic function and overall satisfaction with sexual experience (vs placebo p <0.0009). Significant improvement in the satisfaction rate with erection hardness were demonstrated for each vardenafil dose compared with placebo (p <0.0001). Vardenafil was generally well tolerated. Common adverse events were headache, vasodilatation and rhinitis. CONCLUSIONS: In this difficult to treat population of men with erectile dysfunction subsequent to NS-RRP on demand treatment with vardenafil during a 3-month period significantly improved key aspects of the sexual experience important to patient quality of life.     

Tadalafil improved erectile function at twenty-four and thirty-six hours after dosing in men with erectile dysfunction: US trial

In a previous study assessing tadalafil for the treatment of erectile dysfunction (ED), tadalafil 20 mg was shown to improve erectile function for up to 36 hours vs placebo. This study sought to demonstrate the effectiveness of both 10- and 20-mg tadalafil vs placebo at 2 prespecified assigned times of 24 and 36 hours postdosing. This double-blind, placebo-controlled, parallel-group study randomized 483 men with ED into 6 groups according to a combination of treatment (placebo, tadalafil 10 or 20 mg) and assigned time (24 or 36 hours) for intercourse attempts. Patients were stratified by baseline ED severity based on Erectile Function Domain scores. The study had 4 phases: a 4-week run-in (no ED medication taken); a 2- to 4-week equilibration (dosing as needed); a 4- to 6-week assessment; and a 6-month open-label extension. During the assessment phase, men took a total of 4 doses of study medication, each dose separated by more than or equal to 7 days. Efficacy was measured as the mean per-patient percentage of successful intercourse attempts (Sexual Encounter Profile Diary Question 3: SEP3) during the assessment phase. Men taking either 10- or 20-mg tadalafil had a significant increase in SEP3 from baseline scores vs placebo at both 24 hours (P = .038 and <.001 for 10 and 20 mg, respectively) and 36 hours (P < .001 for both doses) postdose. The mean per-patient percentages of successful intercourse attempts for the 24-hour time point were 41.8%, 55.8%, and 67.3% for placebo and tadalafil 10 and 20 mg, respectively; for the 36-hour time point, the mean per-patient percentages were 32.8%, 56.2%, and 61.9% for placebo and tadalafil 10 and 20 mg, respectively. The most common treatment-emergent adverse events were headache, back pain, dyspepsia, and nasopharyngitis. Both 10- and 20-mg tadalafil improved erectile function for up to 36 hours postdosing in men with ED of varied severity.     

Long-term treatment of erectile dysfunction with a phosphodiesterase-5 inhibitor and dose optimization based on nocturnal penile tumescence

Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands

OBJECTIVE

To test the hypothesis that a variable dosage of the oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil (25, 50, 100 mg) or vardenafil (5, 10, 25 mg) determined according to results obtained from nocturnal penile tumescence and rigidity (NPTR, RigiScan), given nightly for 1 year, can improve spontaneous erectile function (EF) in men with mild‐to‐moderate arteriogenic erectile dysfunction (ED); this regimen was compared with a fixed daily dosage of sildenafil 25 mg or vardenafil 5 mg.

PATIENTS AND METHODS

In a prospective open‐label, parallel‐group trial 154 men with ED were randomized either to fixed low‐dose sildenafil 25 mg or vardenafil 5 mg (group 1) or to the lowest erectile dosage of sildenafil (25, 50 or 100 mg) or vardenafil (5, 10 or 20 mg) (group 2) provoking an erectile event as measured by NPTR nightly for 1 year. The EF domain of the International Index of Erectile Function (IIEF) was assessed before and 1 year after the beginning of treatment, and at 4 weeks after ending treatment.

RESULTS

After 1 year, 27 of 63 (64%) evaluable men in group 1 had an EF domain score in the normal range, vs 46 of 61 (75%) men in group 2. After the subsequent 4‐week wash‐out phase, both groups continued to have improved EF domain scores; 22 of 63 (35%) men in group 1 still had a score in the normal range, whereas 38 of 61 (62%) in group 2 had a normal score. The EF domain score in group 1 and 2 improved significantly after 1 year of treatment, from 13.6 to 18.9, and 15.1 to 23.9, respectively (P < 0.01). After the subsequent 4‐week wash‐out phase, men from both groups maintained this significant level of EF, at 17.1 and 22.4, respectively (P < 0.05).

CONCLUSION

Nightly PDE5‐inhibitor treatment 1 year in a dosage determined by NPTR measurements results in better EF than giving a fixed dosage of sildenafil (25 mg) or vardenafil (5 mg). This improvement persisted for >4 weeks beyond the end of treatment. The results from this open‐label, randomized trial warrant verification under double‐blind, placebo‐controlled conditions.     

Efficacy and safety of tadalafil in a Western European population of men with erectile dysfunction

Section Editor Michael G. Wyllie Panel of Advisors Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA

OBJECTIVE

To evaluate, in a randomized, double‐blind, placebo‐controlled, multicentre trial, the safety and efficacy of on‐demand tadalafil (an oral phosphodiesterase type‐5 inhibitor approved in many countries for treating erectile dysfunction, ED) in a Western European population of men with mild‐to‐severe ED.

PATIENTS AND METHODS

Patients were randomized according to baseline severity of ED in a ratio of 3 : 1 to receive either tadalafil 20 mg or placebo for 12 weeks. Primary efficacy endpoints were mean changes from baseline to endpoint (12 weeks) in the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and percentages of ‘Yes’ responses to Sexual Encounter Profile (SEP) diary Question 2 (‘Were you able to insert your penis into your partner's vagina?’) and Question 3 (‘Did your erection last long enough for you to have successful intercourse?’). Secondary endpoints included mean changes from baseline to endpoint in IIEF Intercourse Satisfaction and Overall Satisfaction domains, selected questions of the IIEF, and the percentage of ‘Yes’ responses to Global Assessment Questions (GAQ) at the last visit. Other analyses included the percentage of patients in each treatment group at endpoint with IIEF EF domain scores in the normal range (>26), the frequency of intercourse attempts and mean per‐patient intercourse success rate at various times after dosing.

RESULTS

The mean age of the patients was 53 years and 80% had a history of ED of ≥ 1 year. The mean baseline EF domain score was 13.5, with 40.5% of patients in the severe category. Tadalafil improved mean EF domain scores by 11.1, vs 0.4 for placebo (P < 0.001). In addition, 73.9% of sexual intercourse attempts were successful (SEP‐Q3) in tadalafil‐treated patients, compared with 29.9% in placebo‐treated patients during the period after baseline (P < 0.001). Tadalafil significantly improved the mean IIEF intercourse satisfaction (5.1, tadalafil; 1.1, placebo) and overall satisfaction domain scores (3.9, tadalafil; 0.5, placebo), P < 0.001. GAQs used to assess the overall effect of the treatment indicated that tadalafil was superior to placebo (P < 0.001) in improving erections (82.1%, tadalafil; 23.1%, placebo) and sexual activity (78.6% and 17.3%). The most common treatment‐emergent adverse events more frequent (>2%) with tadalafil than placebo were headache, dyspepsia, flushing, back pain, pain in limb and myalgia. These adverse events were mostly mild to moderate.

CONCLUSIONS

Tadalafil improved erectile function and was well tolerated when taken by men from Western Europe with mild‐to‐severe ED.

     

Comparison of the efficacy and safety of sildenafil citrate (Viagra) and oral phentolamine for the treatment of erectile dysfunction

This open-label, multi-center study from Mexico compared the efficacy and safety of oral sildenafil and phentolamine in men with erectile dysfunction. Patients received sildenafil (25-100 mg; n=123) or phentolamine (40 mg; n=119) for 8 weeks, and efficacy was assessed using the International Index of Erectile Function (IIEF) as well as two global efficacy questions. Mean scores for the erectile function domain of the IIEF were significantly higher for sildenafil (27.23 +/- 0.62; P=0.0001) than for phentolamine (19.35 +/- 0.66). Approximately twice as many men receiving sildenafil had successful attempts at sexual intercourse (88% vs 42%), improved erections (95% vs 51.1%), and improved ability to have sexual intercourse (94.4% vs 46.4%) compared with phentolamine. The most common adverse events included rhinitis, headache, tachycardia, and nausea, with a higher frequency reported in patients receiving phentolamine than sildenafil (41% vs 33%), with the exception of headache, which was reported more frequently in sildenafil users. Overall, sildenafil was more effective and appeared to be better tolerated than phentolamine for the treatment of erectile dysfunction.     

Efficacy and safety of sildenafil for treating erectile dysfunction in patients on dialysis

OBJECTIVE: To assess the efficacy of sildenafil for erectile dysfunction (ED) in patients on haemodialysis (HD) or peritoneal dialysis (PD), as men with end-stage renal disease (ESRD) often have sexual dysfunction (up to 82% among those on chronic dialysis). PATIENTS AND METHODS: Forty-one patients with ED and in ESRD participated in an open-label prospective study. Thirty patients on HD and 11 on PD were asked to complete the International Index of Erectile Function (IIEF) and Fugl-Meyer life-satisfaction scale before and after sildenafil treatment. A total score in the erectile function domain of < or = 25 was accepted as indicating ED. All patients were started on a 25-mg dose, which was increased to 50 mg if there was no response after two trials. In addition, the overall efficacy question was used to evaluate satisfaction, and patients reported any side-effects during treatment. RESULTS: The erectile function and intercourse satisfaction domains improved significantly in both groups (P < 0.01). After sildenafil treatment, two-thirds of those on HD (20/30) and nine of the 11 on PD recovered their erectile function. The pretreatment scores on the IIEF and four domains (except sexual desire) of those responding were significantly higher than in those not responding (P < 0.05). The satisfaction rate on the overall efficacy question was 80% and 82% for the HD and PD groups, respectively. At least one side-effect was seen in 17 patients (43%); one had severe hypotension in the PD group. Overall, mild headache (seven patients, 18%) and flushing (12, 30%) were reported most often. CONCLUSIONS: Sildenafil is a safe and satisfactory drug for improving erectile function in patients with ESRD. Patients were satisfied whether treated by HD or PD. Pretreatment scores on the IIEF may be useful for predicting the success of treatment.