Efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic syndrome: results of a randomized, placebo-controlled trial.

INTRODUCTION: The prevalence of erectile dysfunction (ED) is increased in men with metabolic syndrome compared with the general population. AIM: The aim of this study was to evaluate the efficacy and safety of vardenafil vs. placebo in men who had ED and metabolic syndrome. METHODS: This was a 12-week, double-blind, randomized, multicenter, parallel-group, placebo-controlled prospective study in men with ED and metabolic syndrome (assessed by the International Diabetes Federation criteria). Vardenafil was administered at a starting dose of 10 mg, which could be titrated to 5 mg or 20 mg after 4 weeks, depending on efficacy and tolerability. MAIN OUTCOME MEASURES: Primary efficacy measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile (SEP) diary questions 2/3. Secondary efficacy measures included SEP1, a diary question assessing ejaculation, the percentage of men achieving "return-to-normal" erectile function, and the percentage of men who titrated to a different dose. Adverse events (AEs) were recorded throughout the study. RESULTS: The intent-to-treat population included 145 men (vardenafil, N = 75; placebo, N = 70). Baseline least squares IIEF-EF domain scores were low (vardenafil: 12.0; placebo: 12.7), indicative of moderate-to-severe ED. Vardenafil was statistically significantly superior to placebo for all primary efficacy measures (P < 0.0001) and showed nominally statistically significant superiority compared with placebo for SEP1/ejaculation success rates (P = 0.0003 and P < 0.0001, respectively) and the percentage of subjects reporting "return-to-normal" erectile function (P = 0.0004). Treatment-emergent AEs were mild-to-moderate in severity and consistent with the known AE profile of phosphodiesterase type 5 inhibitors. CONCLUSIONS: This is the first study to assess the efficacy and safety of vardenafil, taken alone, for ED therapy in a population of men who all had metabolic syndrome. Although baseline erectile function in these patients was low, vardenafil treatment was associated with significant improvements in erectile function and rates of successful intercourse, and was well tolerated.

Efficacy and safety of an orodispersible vardenafil formulation for the treatment of erectile dysfunction in elderly men and those with underlying conditions: an integrated analysis of two pivotal trials.

INTRODUCTION: Men with erectile dysfunction (ED) are typically older and have one or more underlying cardiovascular conditions. AIM: To determine the efficacy and safety of a new orodispersible tablet (ODT) formulation of vardenafil for the treatment of ED, and whether age, or the presence of underlying conditions affects treatment outcomes. METHODS: This is an integrated analysis of data from two phase III, double-blind, multicenter, randomized, parallel-group, placebo-controlled studies that compared 10 mg on-demand vardenafil ODT with placebo in a general population of men with ED, stratified so that approximately 50% of patients were aged ≥ 65 years. Results were reported by age (<6 5 vs. ≥ 65 years) and presence/absence of diabetes, dyslipidemia, or hypertension. MAIN OUTCOME MEASURES: Primary measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3). RESULTS: Of the 701 men randomized (51% aged ≥ 65 years), 686 were included in the intent-to-treat population (placebo, n = 334; vardenafil ODT, n = 352). Vardenafil ODT was significantly superior to placebo for all primary efficacy measures, regardless of age, baseline ED severity, or underlying condition (P < 0.0001 for vardenafil vs. placebo for each endpoint). IIEF-EF scores and SEP2/3 success rates in older patients and men with underlying conditions were not significantly different to those of younger patients or men without underlying conditions. Adverse events (AEs) were mostly mild to moderate in severity, occurring with higher incidence in the vardenafil vs. placebo group. The most frequently reported drug-related AEs in the vardenafil group were headache, flushing, nasal congestion, dizziness, and dyspepsia, consistent with the known safety profile of phosphodiesterase type 5 inhibitors. CONCLUSIONS: Vardenafil ODT significantly improves erectile function in men with ED regardless of age, baseline ED severity, or underlying condition.

The POTENT I randomized trial: efficacy and safety of an orodispersible vardenafil formulation for the treatment of erectile dysfunction.

INTRODUCTION: Orodispersible tablet (ODT) formulations offer improved convenience over film-coated formulations and are preferred by many patients. AIM: To investigate the efficacy and safety of an ODT formulation of 10 mg vardenafil administered on demand vs. placebo in a general population of men with erectile dysfunction (ED). METHODS: This was a 16-week, double-blind, multicenter, randomized, parallel-group, placebo-controlled study conducted at 40 centers across Europe and South Africa. Eligible participants were men aged > or = 18 years with ED for at least 6 months, in a stable heterosexual relationship for at least 6 months, highly motivated to obtain ED treatment, and making at least four attempts at sexual intercourse on four separate days, of which at least half were unsuccessful. Subjects were randomized to receive 12 weeks of treatment with either 10 mg vardenafil ODT on demand or placebo, and each treatment group was stratified such that approximately half of the subjects were aged > or = 65 years. MAIN OUTCOME MEASURES: Primary measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and the Sexual Encounter Profile questions 2 and 3 (SEP2, SEP3). Secondary measures included SEP diary questions 1, 4, 5, and 6; the Treatment Satisfaction Scale; and the Global Assessment Question. RESULTS: Of the 409 men enrolled (54.8% aged > or = 65 years), 355 were included in the intent-to-treat population (vardenafil ODT, N = 183; placebo, N = 172). Vardenafil ODT therapy was statistically significantly superior to placebo for all primary (IIEF-EF, SEP2, SEP3) and secondary efficacy measures (all P < 0.0001). The incidence and type of treatment-related adverse events with vardenafil 10 mg ODT were comparable with those of the film-coated tablet formulation. CONCLUSIONS: Treatment with 10 mg vardenafil ODT, taken on demand, significantly improved erectile function and was well tolerated in a broad population of men with ED.

Vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Alpha-blockers, the current common treatment for lower urinary tract symptoms (LUTS), are also used to treat bladder outlet obstruction (BOO), but the effect is not as clinically significant as in LUTS. All currently marketed phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to significantly affect LUTS, although BOO-related efficacy has not been determined. Therefore, the extent of a causal relationship between LUTS and underlying benign prostatic enlargement (BPE) is questionable. LUTS may also be interpreted as symptoms related to detrusor overactivity, especially when no significant BOO is associated with BPE. Research is required to understand the efficacy of PDE5 inhibitors in LUTS but not in BOO. For vardenafil, nonclinical experiments and initial, preliminary clinical data suggest that the underlying effect may occur on the detrusor and not the prostate.

Comparable efficacy of once-daily versus on-demand vardenafil in men with mild-to-moderate erectile dysfunction: findings of the RESTORE study.

BACKGROUND: Phosphodiesterase (type) 5 (PDE5) inhibitors are currently administered on demand for treatment of erectile dysfunction (ED). Once-daily dosing has been suggested to benefit patients. OBJECTIVE: To determine whether daily vardenafil use provides added clinical benefits to patients compared with on-demand dosing. DESIGN, SETTING, AND PARTICIPANTS: In this placebo-controlled, double-blind, multicentre parallel-group study, men with mild-to-moderate ED were randomised to 24 wk of treatment, followed by a 4-wk washout. INTERVENTION: Patients were randomised to receive once-daily vardenafil 10mg plus on-demand placebo for 12 or 24 wk, or once-daily placebo plus on-demand vardenafil 10mg for 24 wk. MEASUREMENTS: Primary efficacy variable was the between-group difference in change in International Index of Erectile Function-Erectile Function domain (IIEF-EF) score from baseline to end of washout. Secondary variables included change from baseline in proportion of positive respondents to Sexual Encounter Profile questions and in satisfaction with treatment as assessed with the Treatment Satisfaction Scale (TSS). RESULTS AND LIMITATIONS: LS mean changes from baseline in IIEF-EF scores were 2.02, 2.29, and 2.63 for vardenafil 12 wk once daily, 24 wk once daily, and 24 wk on demand, respectively. After washout, the trend was towards improved IIEF-EF scores in the on-demand group (20.58 [+/-0.96]) versus both once-daily groups (12 wk, 19.88 [+/-0.93]; 24 wk, 20.11 [+/-0.94]). Furthermore, there were no significant between-group differences in the percentage of patients with "normal" erectile function. TSS analyses demonstrated no significant differences between treatment groups. This study recruited patients with mild-to-moderate ED; therefore, the results may not be the same as in patients with severe ED. CONCLUSIONS: Once-daily vardenafil did not produce greater sustained effects on EF than on-demand vardenafil in men with mild-to-moderate ED, suggesting that daily dosing of PDE5 inhibitors does not produce sustained clinical benefits beyond cessation of treatment above those observed with on-demand administration.

A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is associated with bothersome lower urinary tract symptoms (LUTS) and reduced patient quality of life (QoL). Phosphodiesterase (type) 5 (PDE5) inhibitors such as vardenafil are commonly used for the treatment of erectile dysfunction (ED), but have also been shown to improve the symptoms of BPH. This randomised, double-blind, placebo-controlled study investigated the effects of vardenafil on LUTS and QoL in men with BPH/LUTS, with or without concomitant ED. METHODS: Men aged 45-64 yr with BPH/LUTS and an International Prostate Symptom Score (IPSS) > or =12 were randomised to receive either 10mg vardenafil or placebo twice daily. LUTS were assessed with the use of two primary efficacy parameters, IPSS score and maximum urinary flow rate (Qmax), as well as postvoid residual (PVR) urine volume; ED was measured with the use of the erectile function (EF) domain score of the International Index of Erectile Function (IIEF-EF); and QoL was assessed with the Urolifetrade mark QoL-9 questionnaire. RESULTS: After 8 wk of treatment, there was a significant improvement in the IPSS total score in the vardenafil group compared with placebo (-5.9 and -3.6, respectively; p=0.0013). Nominally significant improvements in irritative and obstructive IPSS subscores (p=0.0017 and p=0.0081, respectively), EF (p=0.0001), and Urolife QoL-9 (p<0.0001) were also associated with vardenafil treatment. Qmax and PVR urine volume did not change significantly with treatment, although baseline values were already considered close to normal. Vardenafil was generally well tolerated, with most adverse events considered mild or moderate in severity. CONCLUSIONS: Vardenafil treatment significantly improved LUTS, EF, and QoL in men with BPH/LUTS. Vardenafil may be considered a promising treatment option for men with symptoms secondary to BPH.

Efficacy of vardenafil in men with erectile dysfunction: a flexible-dose community practice study.

OBJECTIVE: To determine the efficacy and tolerability of flexible dosing with vardenafil in a broad population of men with erectile dysfunction (ED). METHODS: 10-week, open-label, flexible-dose study starting with vardenafil 10 mg, titrating to 5 mg or 20 mg at weeks 2 and 6 based on efficacy and tolerability, set in 78 community practice centers in Germany and France. Participants comprised 398 men aged > or =18 years with ED. Main outcome measures were self-reported improvement in erections according to a Global Assessment Question (GAQ), diary questions from the Sexual Encounter Profile (SEP2 and SEP3), and the erectile function domain score from the International Index of Erectile Function (IIEF) questionnaire. RESULTS: In a last observation carried forward (LOCF) analysis, a total of 92% (336/366) of men with ED reported an improvement of erections according to the GAQ. Per-patient success rates for penetration (SEP2) and maintenance (SEP3) of erection for intercourse were 89% (348/390) and 78% (303/390), respectively. Mean erectile function domain scores increased from 13.9 at baseline to 25.9 at LOCF. Vardenafil was generally well tolerated; headache (6%, 25/398) and flushing (6%, 24/398) were the most frequent adverse events. CONCLUSIONS: In this community practice setting, vardenafil was shown to be a highly effective and generally well-tolerated treatment for men with ED when dosing was titrated by the physician to individual patient requirements.

Earliest time to onset of action leading to successful intercourse with vardenafil determined in an at-home setting: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Vardenafil, a potent and selective oral PDE5 inhibitor, is efficacious and generally well-tolerated in men with erectile dysfunction (ED). Of considerable interest to patients and physicians is an understanding of the time required after dosing to attain penile erection sufficient for successful sexual intercourse. AIM: To determine the earliest time to onset of action of vardenafil 10 and 20 mg leading to successful intercourse compared to placebo in men with ED. METHODS: A prospective, randomized, double-blind, parallel-group, at-home study of 732 men with ED (mean age 55.5 years) was conducted at 64 sites in North America and Europe. Following a 4-week run-in period, patients were randomized to either vardenafil 10 (N = 237) or 20 mg (N = 248) or placebo (N = 247) to be taken on demand over 4 weeks. Using a stopwatch, patients recorded the elapsed time from dosing to attainment of an erection perceived to be adequate for penetration that led to intercourse completion. Earliest time of onset was defined as the fastest time among the first four doses for each patient. Time points from 25 to 5 minutes were tested for significance (alpha = 0.025) using a backward stepping procedure. RESULTS: Mean baseline erectile function domain score (13.4) indicated moderate ED. Within 25 minutes after dosing, 50%/53% of men on vardenafil 10/20 mg had at least one erection in the first four doses perceived to be sufficient for penetration with subsequent intercourse completion compared to 26% on placebo (P < 0.0001). A statistically superior response to vardenafil vs. placebo was observed in these responders at all times >or= 10 and >or= 11 minutes (P < 0.025) in the 10 and 20 mg groups, respectively. In a retrospective analysis using time intervals of