title: Efficacy and tolerability of vardenafil for treatment of erectile dysfunction in patient subgroups. A comparative, crossover study of the efficacy and safety of sildenafil and apomorphine in men with evidence of arteriogenic erectile dysfunction Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. 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 Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Switching from long-term treatment with self-injections to oral sildenafil in diabetic patients with severe erectile dysfunction. Vardenafil increases penile rigidity and tumescence in erectile dysfunction patients: a RigiScan and pharmacokinetic study Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy.
abstract: OBJECTIVES To assess whether vardenafil would improve  erectile function  irrespective of etiology , baseline severity , or patient age . The consistency of the response over time was also evaluated . METHODS A multicenter , r and omized , double-blind , placebo-controlled at-home study of vardenafil treatment ( 5 , 10 , and 20 mg ) was performed . This secondary analysis compared the mean International Index of Erectile Function ( IIEF ) erectile function domain scores of various subgroups at 12 weeks of treatment . These population s included organic , psychogenic , or mixed etiologies ; mild , moderate , or severe baseline severity ; and four age groups ( younger than 45 , 45 to 55 , 56 to 65 , and older than 65 years ) . In addition , all IIEF domains were compared at sequential 4-week periods , before and during treatment . RESULTS In the 580 men of the intent-to-treat population , the mean erectile function domain scores were statistically greater than placebo , irrespective of etiology , baseline severity , or age . This was seen at all dosages . Compared with placebo , vardenafil statistically improved the IIEF domain scores of erectile function , orgasmic function , intercourse satisfaction , and overall satisfaction after 4 weeks of treatment , and these improvements were maintained for 12 weeks . The rates of the most common adverse events ( headache , flushing , and dyspepsia ) were either constant or declined over time ; they were generally mild to moderate and transient in nature . CONCLUSIONS Vardenafil improved  erectile function  regardless of the general etiology , baseline severity of erectile dysfunction , or patient age . Improvements in erectile function and other key IIEF domains were consistently seen throughout the study 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 result ing 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 χ2 , 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 OBJECTIVE This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction ( ED ) in men with diabetes . RESEARCH DESIGN AND METHODS In this prospect i ve multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial , 452 patients with diabetes ( type 1 or type 2 ) and ED were r and omized to take 10 or 20 mg vardenafil or placebo as needed for 12 weeks . Efficacy responses were assessed by International Index of Erectile Function domain scores , rates of vaginal penetration and successful intercourse , and a global assessment question ( GAQ ) about erection improvement during the previous 4 weeks . RESULTS After 12 weeks of treatment , a dose-dependent ( P = 0.02 ) improvement in erections was noted for the GAQ , with 57 and 72 % of men taking 10 mg or 20 mg vardenafil , respectively , reporting improved erections , in contrast to 13 % after taking placebo ( P < 0.0001 ) . For the erectile function domain , dose-dependent ( P = 0.03 ) final scores for the 10- and 20-mg dose were 17.1 and 19.0 compared with 12.6 for placebo ( P < 0.0001 ) . Both vardenafil doses significantly enhanced the rates of successful penetration ( P < 0.0001 ) and successful intercourse ( P < 0.0001 ) compared with placebo . Vardenafil treatment was effective in increasing intercourse success rates at all levels of baseline ED severity , at each level of plasma HbA(1c ) , and for type 1 and 2 diabetes . Treatment-emergent adverse events were primarily mild to moderate headache ( < or=13 % ) , flushing ( < or=10 % ) , and rhinitis ( < or=10 % ) . CONCLUSIONS Vardenafil statistically improved erectile function and was generally well tolerated in these diabetic patients with ED 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 , r and omized , 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 result ed in a high efficacy and low adverse-event profile in a population with mixed ED etiologies Sildenafil ( Viagra , UK-92,480 ) is a novel oral agent under development for the treatment of  penile erectile dysfunction .  Erection is dependent on nitric oxide and its second messenger , cyclic guanosine monophosphate ( cGMP ) . However , the relative importance of phosphodiesterase ( PDE ) isozymes is not clear . We have identified both cGMP- and cyclic adenosine monophosphate-specific phosphodiesterases ( PDEs ) in human corpora cavernosa in vitro . The main PDE activity in this tissue was due to PDE5 , with PDE2 and 3 also identified . Sildenafil is a selective inhibitor of PDE5 with a mean IC50 of 0.0039 microM. In human volunteers , we have shown sildenafil to have suitable pharmacokinetic and pharmacodynamic properties ( rapid absorption , relatively short half-life , no significant effect on heart rate and blood pressure ) for an oral agent to be taken , as required , prior to sexual activity . Moreover , in a clinical study of 12 patients with erectile dysfunction without an established organic cause , we have shown sildenafil to enhance the erectile response ( duration and rigidity of erection ) to visual sexual stimulation , thus highlighting the important role of PDE5 in human penile erection . Sildenafil holds promise as a new effective oral treatment for penile erectile dysfunction OBJECTIVE To assess the efficacy of oral sildenafil in diabetic men with severe erectile dysfunction ( ED ) , who are successfully treated with intracavernous injections of  vasoactive drugs . METHODS 81 impotent diabetic men ( 29 with type 1 and 52 with type 2 ) were treated for 1 - 7 years with  self-injections . 13 men were treated with 10 microg and 15 with 20 microg of prostagl and in E1 ( PGE1 ) , and 53 with a mixture of PGE1 20 microg and papaverine 7.5 - 40 mg ( MIX ) . After a 1-week washout period , they changed to oral sildenafil in titrating doses up to 100 mg . The change was successful if the man achieved an erection and penetration even once . RESULTS Sildenafil was discontinued in 23 men because of insufficiency . Eleven men ( 13.6 % ) , all with type 2 diabetes , responded to sildenafil ( 10 previously treated with 10 microg and 1 with 20 microg of PGE1 , none treated with MIX ) . Thus , 39.2 % of the treated with PGE1 responded to oral sildenafil . The response was influenced by the age , the type of diabetes ( type 2 ) and the kind of the previously injected drug ( PGE1 10 microg ) ; it was not influenced by the duration of diabetes , ED and treatment with self-injections . CONCLUSIONS Despite the well documented efficacy of sildenafil , self-injections continue to be the solely effective therapeutic modality in many diabetic men afflicted by severe ED . Only the younger men with non-insulin-dependent diabetes , treated with low doses of PGE1 are more likely to respond to oral sildenafil and change treatment . Men with insulin-dependent diabetes or treated with mixtures of vasoactive drugs are not likely to respond to oral sildenafil Abstract The pharmacodynamic effect on penile rigidity and tumescence and the pharmacokinetic properties of single oral doses of 10 and 20 mg vardenafil , a new PDE5-inhibitor , were investigated in 21 erectile dysfunction patients . Patients were evaluated with RigiScan on three occasions in a r and omized , placebo-controlled , double-blind crossover fashion , while receiving visual sexual stimulation . Relative to placebo , a single dose of 10 mg vardenafil led to a mean increase in the duration of > 60 % penile rigidity of 24.4 min ( 95 % CI : 7.4 to 41.3 ) at the base and of 24.8 min ( 8.5 to 41.1 ) at the tip . For the 20-mg dose , the increase in duration of > 60 % penile rigidity relative to placebo was 37.2 min ( 20.2 to 54.1 ) at the base and 28.7 min ( 12.7 to 44.7 ) at the tip . Single doses of 10 and 20 mg vardenafil led to a rapid rise in the plasma concentrations of vardenafil , with a median tmax of 0.9 h and 0.7 h and a geometric mean Cmax of 9.1 μg/l ( geometric SD=1.63 ) and 20.9 μg/l ( geometric SD=1.83 ) , respectively . In the post-absorptive phase , the concentrations declined with an average terminal t1/2 of 4.2 h ( geometric SD=1.27 ) and 3.9 h ( geometric SD=1.31 ) . The systemic exposure  of vardenafil expressed as AUC normalized for dose and body weight was dose-proportional ( associated 90 % CI : −4 to 30 % ) as well as Cmax ( associated 90 % CI : −12 to 33 % ) . The treatments were well tolerated . There was a small , clinical ly irrelevant reduction in blood pressure with a small compensatory rise in heart rate . There were no electrocardiographic effects or relevant changes of the safety laboratory screens . The observed pro-erectile properties , pharmacokinetic characteristics and safety profile make vardenafil a suitable c and i date for further evaluation in the treatment of erectile dysfunction PURPOSE More than one-third of men may experience erectile dysfunction ( ED ) after nerve sparing radical retropubic prostatectomy . The efficacy and safety of vardenafil , a potent , selective , phosphodiesterase 5 inhibitor , was assessed for the treatment of ED after radical prostatectomy . MATERIAL S AND METHODS In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were r and omized to take placebo , or 10 or 20 mg vardenafil .  Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function , diary questions measuring vaginal penetration and intercourse success rates , and a global assessment question ( GAQ ) on erection . RESULTS Of the intent to treat population 70 % had severe ED ( erectile function less than 11 ) at baseline . After 12 weeks both vardenafil doses were significantly superior to placebo ( p < 0.0001 ) for all efficacy variables . Improved erections ( based on GAQ ) were reported by 65.2 % and 59.4 % of patients on 20 and 10 mg vardenafil , respectively , and by only 12.5 % of patients on placebo ( p < 0.0001 ) . Among men with bilateral neurovascular bundle sparing , positive GAQ responses were reported by 71.1 % and 59.7 % of patients on 20 and 10 mg vardenafil , respectively , versus 11.5 % of those on placebo ( p < 0.0001 ) . The average intercourse success rate per patient receiving 20 mg vardenafil was 74 % in men with mild to moderate ED and 28 % in men with severe ED , compared to 49 % and 4 % for placebo , respectively . Few adverse events were observed . They were generally mild to moderate headache , flushing and rhinitis . CONCLUSIONS In men with severe ED after nerve sparing radical retropubic prostatectomy , vardenafil significantly improved key indices of erectile function
target: These efficacy variables appeared greater at higher doses , although there are no significant differences between 10 and 20 mg dose .
  Specific adverse events with vardenafil  included flushing , dyspepsia , headache , and rhinitis .
  Vardenafil was not significantly associated with serious cardiovascular events or death .
  Vardenafil , in all treatment regimens , shows to possess superior efficacy to placebo in the treatment of patients with erectile dysfunction .
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