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.

Time to onset of action of vardenafil: a retrospective analysis of the pivotal trials for the orodispersible and film-coated tablet formulations.

INTRODUCTION: Patients and physicians consider a rapid onset of action to be an important attribute of oral pharmacotherapy for erectile dysfunction. AIM: To investigate the time to onset of action of a new orodispersible tablet (ODT) formulation of vardenafil. METHODS: A post hoc integrated analysis was performed on data from two 12-week, double-blind, multicenter, randomized, parallel-group, placebo-controlled phase III trials of 10 mg vardenafil ODT. Data for the vardenafil film-coated tablet were generated from a retrospective integrated analysis at week 12 of four double-blind, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled phase III trials. Time intervals (in 15-, 30-, and 60-minute increments, up to ≥6 hours after study medication intake) were determined for the period between dosing and start of sexual activity (with the intention of intercourse). MAIN OUTCOME MEASURES: The total number of sexual intercourse attempts and Sexual Encounter Profile question 3 (SEP3) success rates were calculated per time interval. RESULTS: Within 15 minutes postdosing, mean per-patient SEP3 success rates were 62.5% (vardenafil ODT) vs. 29.4% (placebo), with corresponding overall SEP3 success rates of 59.8% and 38.2%. In this time interval, 5.3% vs. 2.8% of all sexual activity attempts were initiated by subjects taking vardenafil ODT (n = 89) or placebo (n = 62), respectively. At 16-30 minutes postdosing, SEP3 success rates were 65.3% and 32.6% (mean per-patient) and 70.2% and 51.0% (overall) for vardenafil ODT vs. placebo, respectively, with a corresponding 10.4% and 8.7% of all sexual activity attempts being made by subjects taking vardenafil ODT (n = 170) or placebo (n = 118). Comparable results were observed for vardenafil 10 and 20 mg film-coated tablet at corresponding time intervals. CONCLUSIONS: Vardenafil ODT shows a rapid onset of action comparable with that of vardenafil film-coated tablet. In those men who begin sexual activity within 30 minutes after dosing, the majority of sexual attempts lead to successful intercourse.

Improvement in sexual quality of life of the female partner following vardenafil treatment of men with erectile dysfunction: a randomized, double-blind, placebo-controlled study.

INTRODUCTION: Erectile dysfunction (ED) impacts on both members of the couple. Female partners of men with ED are more likely to report reduced sexual quality of life than women whose partners do not have ED. AIM: To assess vardenafil efficacy in men with ED and determine the effects of treatment on their female partner's sexual quality of life. METHODS: Study participants comprised men aged 18-64 years with ED and their female partners. Eligible men had ED of ≥6 months' duration and a female partner who was motivated to support their ED treatment. Eligible women had a total Female Sexual Function Index score >23.55, indicating absence of significant sexual dysfunction. Following a 4-week screening period, men were randomized to treatment with vardenafil 10 mg or placebo, which could be titrated to 20 or 5 mg after 4 weeks. MAIN OUTCOMES MEASURES: Primary efficacy variables were question 3 of the Sexual Encounter Profile questionnaire (SEP3) and the quality-of-life domain of the modified Sexual Life Quality Questionnaire (mSLQQ-QOL). RESULTS: The intent-to-treat population included 343 couples, with 168 and 175 men receiving vardenafil or placebo, respectively. Vardenafil treatment significantly improved both erection maintenance and the female partners' sexual quality of life. Least squares (LS) mean SEP3 overall success rates after 12 weeks of treatment were 9.5 (baseline) vs. 67.2 (week 12) and 12.4 (baseline) vs. 24.2 (week 12) in the vardenafil and placebo groups, respectively (P < 0.0001). In female partners, LS mean mSLQQ-QOL scores were 28.8 (baseline) vs. 68.2 (last observation carried forward [LOCF]) in the vardenafil group and 24.6 (baseline) vs. 40.5 (LOCF) in the placebo group (P < 0.0001). CONCLUSIONS: Vardenafil treatment of men with ED improved both their erectile function and the sexual quality of life of their female partners.

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.

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.

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.

The efficacy of hydrotalcite compared with OTC famotidine in the on-demand treatment of gastroesophageal reflux disease: a non-inferiority trial.

BACKGROUND: Antacids and gastric acid inhibitors are effective in the self-treatment of gastroesophageal reflux disease (GERD). The aim was to investigate onset of action of the antacid hydrotalcite compared with the OTC H2-receptor antagonist famotidine in patients suffering from heartburn. MATERIAL/METHODS: A total of 53 patients with endoscopically diagnosed GERD grade 0-1 took part in this open, randomized, parallel-group comparison trial: 26 patients received a single dose of 1000 mg hydrotalcite and 27 patients a single dose of 10 mg famotidine on the occasion of a symptomatic reflux episode. Severity of heartburn and accompanying symptoms were documented on a four-point verbal rating scale (VRS) at baseline and up to four hours after intake. Onset and duration of action were defined by the number of patients experiencing improvement of heartburn from severe or moderate to mild or none compared with baseline. RESULTS: Hydrotalcite was significantly superior (p<0.001) to famotidine in increasing the proportion of responders within the first 45 minutes, starting 10 minutes after drug intake. Between 60 and 120 minutes, both compounds showed equal efficacy. Three hours after intake the response rate was 90.9% for hydrotalcite and 92.0% for famotidine. After four hours the response rates were 86.4% for hydrotalcite and 96.0% for famotidine. In both groups, no adverse events were observed. CONCLUSIONS: The results indicate that hydrotalcite relieves the symptoms of gastroesophageal reflux faster than OTC famotidine and is equally effective for up to two hours. It is a safe and effective self-medication for on-demand treatment of heartburn.

Zuclopenthixol in adults with intellectual disabilities and aggressive behaviours: discontinuation study.

We investigated the effects of zuclopenthixol on aggressive behaviour in patients with intellectual disabilities by randomly withdrawing it after a 6-week period of open treatment. Of the 49 patients responding to the treatment, 39 took part in a randomised withdrawal trial. The placebo subgroup (n=20) showed more aggressive behaviour as indicated by outcomes observed by external raters on the Modified Overt Aggression Scale than did the continuing subgroup (n=19). The results indicate that discontinuation of zuclopenthixolin this population leads to an increase in aggressive behaviour.

The COUPLES-project: a pooled analysis of patient and partner treatment satisfaction scale (TSS) outcomes following vardenafil treatment.

OBJECTIVE: To assess the influence of vardenafil on treatment satisfaction in men with erectile dysfunction (ED) and their female partners. PATIENTS AND METHODS: This was a pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies of flexible-dose vardenafil vs placebo, in men with ED for >/=6 months (n = 788) and their untreated female partners. Measures of efficacy included the Treatment Satisfaction Scale (TSS), International Index of Erectile Function, Erectile Function domain (IIEF-EF), and Sexual Encounter Profile (SEP) questions 2 and 3 (SEP-2, 'Were you able to insert your penis into your partner's vagina?'; and SEP-3, 'Did your erection last long enough for you to have sexual intercourse?'). In addition to the overall analysis, there was a subgroup analysis for potential moderators of response, e.g. whether patients who had undergone previous phosphodiesterase type 5 (PDE-5) treatment. RESULTS: At baseline, least-squares (LS) mean scores for all TSS domains were similar in the vardenafil and placebo groups. After 12 weeks of treatment, vardenafil significantly improved the LS mean score for all domains compared with placebo, among both patients and their female partners (P < 0.0001, 'last'-observation-carried- forward analysis). Absolute between- group differences in LS mean TSS scores (vardenafil - placebo) were: ease of erection (patients 23.4, partners 24.9), erectile function satisfaction (36.7 and 32.9), pleasure from sexual activity (23.0, 23.7), satisfaction with orgasm (27.6, 21.8), confidence to complete sexual activity (28.2, 32.5), and satisfaction with medication (37.4, 35.6). The benefits of vardenafil were greater in men who had undergone previous PDE-5-inhibitor treatment and men aged <45 years, while the overall pattern of benefit was similar in all examined subgroups. There were significant benefits with vardenafil in all other variables (IIEF-EF scores and positive response rates to SEP-2 and SEP-3). CONCLUSIONS: Vardenafil significantly improved treatment satisfaction in men with ED, and in their partners. The results provide further evidence of the validity of the TSS.

Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double-blind, randomized trial.

OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor response to sumatriptan therapy for acute migraine attacks has been documented in the literature, but few controlled trials have investigated the efficacy of an alternative triptan in this subgroup of patients. METHODS: Patients with an International Headache Society diagnosis of migraine who self-described as experiencing at least two unsatisfactory responses to sumatriptan treated their first migraine attack with open-label sumatriptan 50 mg. Patients who did not achieve 2-hour pain relief (improvement of headache from moderate/severe to mild/no headache) were then randomized to treat their second attack with almotriptan 12.5 mg or placebo under double-blind conditions. RESULTS: In the first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief with sumatriptan and were randomized to treatment of their second attack with almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at baseline. Two-hour pain-relief rates were significantly higher with almotriptan compared to placebo (47.5 vs. 23.2%; p < 0.001). A significant treatment effect for almotriptan was also seen in pain-free rates at 2 h (33.3 vs. 14.1%; p < 0.005) and sustained freedom from pain (20.9 vs. 9.0%; p < 0.05). In the second attack, 7.1% of patients in the almotriptan group experienced adverse events compared to 5.1% in the placebo group (p = 0.77). CONCLUSIONS: Almotriptan 12.5 mg is an effective and well-tolerated alternative for patients who respond poorly to sumatriptan 50 mg. A poor response to one triptan does not predict a poor response to other agents in that class.

Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double-blind, randomized trial.

OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor response to sumatriptan therapy for acute migraine attacks has been documented in the literature, but few controlled trials have investigated the efficacy of an alternative triptan in this subgroup of patients. METHODS: Patients with an International Headache Society diagnosis of migraine who self-described as experiencing at least two unsatisfactory responses to sumatriptan treated their first migraine attack with open-label sumatriptan 50 mg. Patients who did not achieve 2-hour pain relief (improvement of headache from moderate/severe to mild/no headache) were then randomized to treat their second attack with almotriptan 12.5 mg or placebo under double-blind conditions. RESULTS: In the first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief with sumatriptan and were randomized to treatment of their second attack with almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at baseline. Two-hour pain-relief rates were significantly higher with almotriptan compared to placebo (47.5% vs 23.2%; P<.001). A significant treatment effect for almotriptan was also seen in pain-free rates at 2 hours (33.3% vs 14.1%; P<.005) and sustained freedom from pain (20.9% vs 9.0%; P<.05). In the second attack, 7.1% of patients in the almotriptan group experienced adverse events compared to 5.1% in the placebo group (P=.77). CONCLUSIONS: Almotriptan 12.5 mg is an effective and well-tolerated alternative for patients who respond poorly to sumatriptan 50 mg. A poor response to one triptan does not predict a poor response to other agents in that class.

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.

Flupenthixol in relapse prevention in schizophrenics with comorbid alcoholism: results from an open clinical study.

Substance use, especially alcoholism, has been recognized as a significant problem in schizophrenic patients, though only a few studies on the effects of pharmacotherapy in these patients have been conducted so far. The thioxanthene neuroleptic flupenthixol, which can be given intramuscularly (i.m.) for improving compliance, has been studied as a possible anti-craving drug both in animal models of alcoholism and some clinical studies. Pilot studies suggest that comorbid schizophrenics with substance use may benefit from treatment with flupenthixol. Efficacy of flupenthixol (10-60 mg i.m.) in reducing alcohol consumption of dual diagnosis patients was studied in an open 6-month clinical trial in 27 schizophrenics with comorbid alcoholism. Twenty-one patients entered the intention-to-treat analysis. Fourteen subjects were completers, 13 dropped out. Six patients completely abstained from alcohol during treatment. Alcohol consumption was significantly reduced compared to baseline (4 weeks before treatment as measured by timeline follow-back interview). In general, while patients showed a marked improvement concerning alcohol consumption, only a slight improvement in psychopathology was recorded. Overall tolerability was good. These data indicate a probable beneficial effect of flupenthixol in schizophrenic patients with comorbid alcoholism. Although the efficacy of flupenthixol as an anti-craving drug in dual diagnosis patients has to be explored in further studies, the drug may be considered a promising medication for these patients.

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