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.     

Yohimbine treatment of organic erectile dysfunction in a dose-escalation trial

Yohimbine has had questionable effects in men with organic erectile dysfunction. We conducted this study to better define the population of men responsive to yohimbine, because tobacco was thought to affect a regimen of yohimbine more than other risk factors. We measured nocturnal penile tumescence with the RigiScan monitor, hormone profiles, answers to the Florida Sexual Health Questionnaire, and clinical responses at baseline and after two different doses of yohimbine in 18 nonsmoking men with erectile dysfunction. Of the 18 men, nine (50%) were successful in completing intercourse in more than 75% of attempts. The yohimbine responders were men with less severe erectile dysfunction as manifested by improved increased rigidity on RigiScan testing, higher Florida Sexual Health Questionnaire scores, and slightly higher levels of serum testosterone. Yohimbine is an effective therapy to treat organic erectile dysfunction in some men with erectile dysfunction.     

Efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction. A comparative crossover study

To compare the efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction (ED), 40 men were studied. Post-injection penile peak systolic velocity was greater than 25 cm s(-1). Twenty men started on apomorphine 2 mg and 20 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg, respectively, if necessary. After a 1-week washout period each group switched to the other treatment mode. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on an event log data. The majority (85%) of the men had concomitant diseases, risk factors for ED and 95% were heavy smokers. The overall success rate of apomorphine was 62.7%, compared with 73.1% of sildenafil (Yates-corrected chi-square, P < 0.0004). The response to apomorphine 2 mg and sildenafil 50 mg was age related. Sildenafil was statistically more effective than apomorphine in impotent men with normal penile Doppler. Given the contraindication of sildenafil in men taking nitrates and the quick time of action of apomorphine, the two drugs are satisfactory first line therapeutic tools in such individuals and the choice should be based on patient's needs and preferences.     

A baseline-controlled,open-label,flexible dose-escalation study to assess the safety and efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction

Although sildenafil citrate (Viagra) has demonstrated effectiveness in the treatment of erectile dysfunction (ED), the dosing regimens often used in clinical trials may not always match those employed in clinical practice. This study was undertaken to further assess the efficacy and safety of sildenafil taken as required in male outpatients 18 years of age and older with ED (n=71). It was conducted as a placebo-baseline-controlled, open-label, flexible dose-escalation study, with sildenafil (25,50, or 100 mg) administered for 8 weeks following a 4-week placebo run-in. Efficacy variables included questions 3 and 4 of the International Index of Erectile Function (IIEF), other IIEF domains, patient event logs, and quality-of-life (QOL) assessments. Treatment with sildenafil resulted in improvements from baseline in all IIEF domains analyzed (all P<0.0001), as well as overall QOL and amelioration of specific sexual and social relationships (all P&<0.0001). Sildenafil was well tolerated. One participant discontinued treatment because of adverse events. Results suggest that flexible dosing with oral sildenafil is safe and has beneficial effects on all indices of erectile function and QOL.     

Sequential administration enhances the effect of apomorphine SL in men with erectile dysfunction

The response to Uprima (apomorphine sublingual, (apo SL)) has been well documented in conventional clinical trials. Apo SL produces a predictable, consistent and durable response across a wide variety of patients. The positive reinforcement of a successful outcome should further support clinical benefit. Apo SL with its rapid onset affords a greater opportunity for spontaneity, which can be an important factor in influencing patient choice. It is recognised that patient counselling and the setting of realistic expectations are vital to a successful outcome. The impact of persisting with sequential treatment on outcome has been calculated from the clinical data. While apo SL is effective de novo in 50% of single doses, additional benefit is observed with repeat dosing. Full benefit may not be achieved until four or more treatments have been taken in an optimal setting. The data also confirm that 3 mg has superior activity. Patients should therefore be encouraged to try a minimum of 4 doses at 3 mg.     

Efficacy and tolerability of vardenafil in Asian men with erectile dysfunction

Aim： To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 （PDE-5） inhibitor, in men of Asian ethnicity with erectile dysfunction （ED）. Methods： In this prospective, double-blind, multinational study, Asian men were randomized to receive vardenafil （10 mg） or placebo （4：1 ratio） for 12 weeks. The primary efficacy variables were the International Index of Erectile Function erectile function domain （IIEF-EF）, and Sexual Encounter Profile （SEP） questions related to penetration and intercourse completion. Significant mean improvements were required in all three measures to show positive benefits of vardenafil treatment. Secondary efficacy variables included the Global Assessment Question （GAQ） on erection improvement. Results： Least-squares mean baseline IIEF-EF domain scores （vardenafil 14.6, placebo 13.4） were consistent with moderate ED. After 12 weeks, vardenafil treatment was associated with significant increases from the baseline in IIEF-EF domain scores compared with the placebo （22.4 vs. 14.3; P 〈 0.001）. Vardenafil was associated with significant improvements from baseline in least squares （LS） mean success rates for SEP-2 （vardenafil 82.2 vs. placebo 43.6; P 〈 0.001） and SEP-3 （vardenafil 66.1 vs. placebo 24.0; P 〈 0.001）. Positive GAQ responses were reported by 81.8% of vardenafil recipients vs. 24.3% of placebo recipients. Adverse events were reported by 25.4% of the vardenafil group, the majority mild and transient. Conclusion： Vardenafil （10 mg） is a highly effective and well-tolerated treatment for moderate ED in Asian men. These results add to the increasing amount of data demonstrating the safety and efficacy of vardenafil for the treatment of ED in a range of patient populations.     

Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. The Apomorphine Study Group

OBJECTIVES: A sublingual (SL) formulation of apomorphine has been developed and found effective in penile erectile dysfunction (ED). This study assessed the efficacy and safety of several doses of apomorphine SL in a dose-optimization schedule compared with placebo. METHODS: In this 8-week, multicenter, double-blind clinical trial, 569 patients were randomized to four groups: a dose-optimization group in which patients began with 2 mg, increased or decreased the dosage as needed for 4 weeks, and thereafter maintained an optimal dose for 4 weeks; two fixed-dose groups of either 5 or 6 mg; and a placebo group. Efficacy was assessed by patient and partner responses to home-use questionnaires about sexual function and activity and by responses to the International Index of Erectile Function and the Brief Sexual Function Inventory. RESULTS: In all apomorphine SL groups, a significantly higher percentage of patients compared with the placebo group achieved and maintained an erection firm enough for intercourse (48% to 53% versus 35% for placebo, P < or =0.001) and a significantly higher percentage of attempts resulted in intercourse (45% to 51% versus 33%, P < or =0.001). The responses to the questionnaires completed by the patients and partners were similar. Apomorphine SL was well tolerated; nausea, the most common side effect, was dose related and diminished substantially during the second 4-week period at all doses. The dose-optimization schedule resulted in fewer adverse events without impacting efficacy. CONCLUSIONS: Apomorphine SL is an effective and safe treatment for ED, with 2 and 4 mg providing the most acceptable therapeutic index.     

Apomorphine sublingual as primary or secondary treatment for erectile dysfunction in patients with spinal cord injury

OBJECTIVES: To evaluate the effectiveness of apomorphine sublingual (SL) 3 mg, as a primary or secondary treatment for erectile dysfunction (ED) in patients with spinal cord injury (SCI), and to determine possible differences in efficacy considering clinical, urodynamic and neurophysiological findings. PATIENTS AND METHODS: The study included 22 patients with chronic SCI and neurogenic ED who were examined physically and by a video-urodynamic evaluation. A neurophysiological evaluation included somatosensory evoked potentials of the pudendal nerve, palmar and plantar sympathetic skin responses and bulbocavernous reflex recordings. Thereafter the patients received 8 tablets of apomorphine SL 3 mg and were asked to complete the International Index of Erectile Function questionnaire before and after treatment. Side-effects, subjective efficacy compared with other treatments and satisfaction with the SL administration were recorded. RESULTS: Of the 22 men, 11 had upper motor neurone lesions (six complete, five incomplete), eight lower motor neurone lesions (seven complete, one incomplete) and three had mixed lesions. In all, 12 patients took sildenafil citrate and five alprostadil intracavernosally beforehand, and five had used nothing to treat their ED. Seven patients had some response and reported that the drug helped them to obtain an erection, but only two reported erections sufficient for intercourse and would agree to continue apomorphine SL as their standard treatment; all the others reported being disappointed. Nine patients reported side-effects. There were no significant correlations for electrophysiological or urodynamic findings and treatment success. Of the 22 patients 20 preferred SL rather than the normal administration. CONCLUSIONS: Apomorphine SL, a D1/D2 dopamine agonist, facilitates erectile function in a heterogeneous group of patients with no significant relationship with any of the assessed urodynamic or electrophysiological variables. The overall low rates of response either for primary or secondary treatment suggests that apomorphine will have limited applicability in patients with SCI.     

盐酸曲唑酮治疗勃起功能障碍的临床研究(附32例报告)

观察盐酸曲唑酮对勃起功能障碍(ED)患者治疗的有效性和安全性,本组设计ED症状评分表对32例患者进行开放式多中心临床研究,结果获得59.4%的有效率,并发现在勃起时间、性交频率、性交满意度方面用药后均有明显改善,不良反应主要为头晕、嗜睡和口干、疲劳,程度均较轻微.认为在累积更多病例更长时间的观察基础上,本药有望成为治疗ED的选择性用药.     

A comparative, crossover study of the efficacy and safety of sildenafil and apomorphine in men with evidence of arteriogenic erectile dysfunction

The aim of the study was to establish and compare the efficacy and safety of sildenafil and apomorphine in men with arteriogenic erectile dysfunction (ED). In all, 43 men with ED and postinjection max penile systolic velocity <25 cm/s in repeated Doppler ultrasonography were included. Of these, 24 men started on apomorphine 2 mg and 19 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg according to effectiveness and tolerability. Safety was evaluated according to adverse events (AEs) and patient withdrawal. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on event log data. The incidence of AEs with apomorphine 3 mg was higher than with sildenafil 100 mg. Two men on apomorphine 3 mg discontinued treatment due to AEs. The overall success rate of sildenafil was 63.7% compared to 32.1% of apomorphine (Pearson chi(2), P<0.01). Of all men, 25 (58.1%) responded to sildenafil 50 mg without the need for dose increase, while only one responded to apomorphine 2 mg. The response to sildenafil 50 mg was age related (analysis of variance, p=0.04). Satisfaction was reported by 76.75 and 13.95% of patients for sildenafil and apomorphine, respectively, but 20.9% were not satisfied with any of the two drugs. In conclusion, this study provides clear evidence that sildenafil, even at 50 mg dose, is more effective than apomorphine 3 mg in men with arteriogenic ED. The fact that one out of five patients is not satisfied with the above-studied drugs shows that new oral agents need to be evaluated for the treatment of this disorder.     

Serum Arginase II level can be a novel indicator for erectile dysfunction in patients with vasculogenic erectile dysfunction: a comparative study

Purpose

The purpose of the study was to compare serum level of Arginase II in patients with vasculogenic erectile dysfunction (ED) versus healthy controls and to assess if its level is affected by severity of ED.

Methods

This is a prospective study that compared Arginase II in 40 patients with ED versus 40 healthy controls. Patients were excluded if they had any pelvic trauma or pelvic surgery, hormonal disorders, Peyronie’s disease, smoking, drug addiction or systemic illnesses. ED was evaluated by the validated Arabic version of the abbreviated five-item form of the international index of erectile function (IIEF-5). Serum arginase II level was assayed using ELIZA. Mann–Whitney, Kruskal–Wallis and Chi-square tests and Spearman correlation were used as appropriate and confirmed by logistic regression model.

Results

22 (55%) patients had DM. 15 (37.5%), 7 (17%), 6 (15%) and 12 (30%) patients suffered from severe, moderate, mild to moderate and mild ED, respectively. The level of serum Arginase II was significantly higher in patients than controls (p?<?0.001) and confirmed by multivariate logistic regression analysis. It also correlated significantly with age (r²?=?0.22; p?<?0.001) and IIEF-5 score (r²?=?0.8; p?<?0.001). Serum Arginase II increased significantly with more severe ED (p?<?0.001). Arginase II was also significantly higher in diabetic patients (p?<?0.001).

Conclusion

Serum level of Arginase II is significantly higher in patients with vasculogenic ED compared to healthy controls. It correlates significantly with age and IIEF-5 and was significantly affected by the severity of ED.

     

Long-term safety and tolerability of tadalafil in the treatment of erectile dysfunction

OBJECTIVE: To assess the long-term safety and tolerability of tadalafil for patients with erectile dysfunction (ED). PATIENTS AND METHODS: This was a multicentre, open-label, 24-month extension trial involving 1173 men with ED. The mean age was 57 (range 23-83) years and 74.8% of patients were taking concomitant medications for comorbid conditions, including diabetes mellitus in 30.5% of men and hypertension in 29.5%. These patients had participated in 1 of 5 previous 8-week or 12-week randomised, double-blind, placebo-controlled tadalafil studies. In the present trial, the starting 10mg dose of tadalafil could be increased to 20mg if the patient could not achieve satisfactory intercourse or reduced to 5mg for an adverse event that was persistent, intolerable and judged by the investigator to be related to tadalafil. RESULTS: Four hundred ninety-three (42.0%) men completed 24 months of treatment. In addition, a further 234 (19.9%) completed 18 months of treatment due to a sponsor decision to reduce the study duration. The total tadalafil exposure was 1676.0 patient-years. Tadalafil was safe and well tolerated. Headache (15.8%), dyspepsia (11.8%), nasopharyngitis (11.4%), and back pain (8.2%) were the most common treatment-emergent adverse events. The rate of discontinuations due to adverse events for this 18-24-month study was 6.3% and the rate for any individual event was <1%. Serious adverse events occurred in 8.6% of patients. No consistent pattern of serious adverse events assessed as causally associated with tadalafil administration was observed. None of the four deaths that occurred during the study was assessed as tadalafil related. There were no clinically significant laboratory or electrocardiographic findings or changes in vital signs in mean baseline-to-endpoint analysis attributable to tadalafil. Tadalafil administration was not causally associated with drug-induced hepatotoxicity, neutropenia, thrombocytopenia, or renal dysfunction. CONCLUSION: Tadalafil at doses of 5, 10, or 20mg taken as needed up to once daily for 18 to 24 months was safe and well tolerated. These findings support the long-term use of tadalafil in the clinical management of erectile dysfunction.     

A double-blind,randomised- placebo,controlled, parallel group,multicentre, flexible-dose escalation study to assess the efficacy and safety of sildenafil administered as required to male outpatients with erectile dysfunction in Korea

The efficacy and safety of sildenafil was evaluated in a randomiSed, double-blind, placebo-controlled, flexible-dose study in Korean men aged 28-78 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months duration. A total of 133 patients were randomised at six centres in Korea to receive either sildenafil (50 mg initially, increased if necessary to l00 mg or decreased to 25 mg depending on efficacy and tolerance) (n=66) or matching placebo (n=67) taken on an 'as needed' basis l h prior to anticipated sexual activity for a period of 8 weeks. At the end of this time, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the International Index of Erectile Function (IIEF) scale, (2) the percentage of successful intercourse attempts, and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P&<0.0001). Treatment-related adverse events occurred in 56.1% of patients receiving sildenafil and 20.9% receiving placebo. The most common adverse events with sildenafil were vasodilatation (flushing), headache and abnormalities in colour vision (31.8, 22.7 and 6.1% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in this population of Korean men appears similar to that reported in other studies in western populations.     

UK multicentre study to assess the safety and tolerability of Neoral in stable renal transplant patients

Abstract  The safety and tolerability of transferring maintained renal transplant patients from Sandim-mun to Neoral is being assessed in a multicentre, open-label, single-arm study. A total of 250 patients has been enrolled and results are available from 75 patients up to 12 months post-transfer. A slight trend to higher mean cyclosporin trough levels was seen in this cohort, but trough levels were unchanged in the sub-group receiving ± 1 dose changes. The mean dose fell by 13 %. Creatinine levels showed a slight overall upward trend. Blood pressure and uric acid were unchanged and adverse events were typical of those seen with Sandim-mun. Neoral was well-tolerated. Data from the full cohort of 250 patients up to 3 months post-transfer support these findings. These results indicate that transfer from Sandim-mun to Neoral is safe and well-tolerated and provides appropriate im-munosuppression at a lower average dose than Sandimmun. The Neoral dose should be adjusted promptly, as required, to maintain the target trough level.     

Double-blind, crossover comparison of 3 mg apomorphine SL with placebo and with 4 mg apomorphine SL in male erectile dysfunction.

OBJECTIVE: To establish the efficacy and safety of a fixed, 3-mg dose of apomorphine SL compared with placebo, and to compare 3 mg with 4 mg apomorphine SL in patients with erectile dysfunction. METHODS: This randomized, double-blind, crossover study included 296 heterosexual men with ED of various etiologies and severities. Two crossover groups were evaluated separately: 3 mg apomorphine SL vs. placebo (n = 194), and 3 vs. 4 mg apomorphine SL (n = 102). The primary efficacy variable was the percentage of attempts resulting in erections firm enough for intercourse; additional variables included the percentage of attempts resulting in intercourse and time to erection. Partner assessments were also analyzed. RESULTS: 3 mg apomorphine SL was significantly more effective than placebo (p<0.001) for the percentage of attempts resulting in erections firm enough for intercourse and resulting in intercourse, as assessed by both patients and partners. Median time to erection was 18.8 min. The 3-mg dose was not significantly different from 4 mg in the evaluation of efficacy variables, but the incidence of adverse events was higher with 4 mg. Nausea was the most common event, reported by 3.3% of patients on 3 mg vs. 14.1% on 4 mg; in the placebo comparison, nausea was reported by 7.0% of patients taking 3 mg apomorphine SL vs. 1.1% of those taking placebo. CONCLUSIONS: 3 mg apomorphine SL was significantly more effective than placebo and comparable to 4 mg, while offering an improved risk-benefit ratio.     

阴茎微循环检测在阳痿诊断中的价值

目的：探讨阴茎头微循环检测在阳痿诊断中的意义。方法：检测２２例勃起功能障碍病人的阴茎微循环,与１７例健康志愿者进行比较。结果：血管性阳痿病人阴茎头微血管密度（２６．８±６．３ｖｓ４７．８±６．２,Ｐ＜０．０１）和异常微血管百分率（３３．２±３．６ｖｓ１２．８±１．３,Ｐ＜０．０１）与对照组相比有显著性差异;心理性阳痿病人的两项指标（微血管密度４７．２±６．８ｖｓ４７．８±６．２,Ｐ＞０．０５;异常微血管百分率１３．１±１．１ｖｓ１２．８±１．３,Ｐ＞０．０５）与对照组相比没有统计学差异。结论：阴茎头微循环障碍与阳痿病人的器质性改变有关,阴茎头微循环检测可用于血管性阳痿的辅助诊断。