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

Abstract

Objective To assess the ef®cacy and safety of sildena®l citrate (Viagra 1 , P®zer 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 ®ve countries were randomized to receive treatment with placebo (156 men) or sildena®l (159 men). Signi®cant 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 sildena®l or matching placebo, which could be increased to 50 mg and then to 100 mg of sildena®l, based on ef®cacy and tolerability. Assessments of ef®cacy 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 ef®cacy 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 sildena®l, respectively. A similar distribution of doses was reported after 26 weeks of treatment. Treatment with sildena®l signi®cantly improved the patients' abilities to achieve and maintain an erection compared with treatment with placebo (P <0.001).Scores for four of the ®ve sexual function domains of the IIEF (erectile function, orgasmic function, intercourse satisfaction and overall satisfaction) also improved signi®cantly (P<0.001). There was a signi®cant 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 sildena®l 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 sildena®l, compared with 8% of patients receiving placebo. Conclusion Sildena®l is an effective and well-tolerated treatment for men with erectile dysfunction of a broad spectrum of aetiology.

The International Index of Erectile Function (IIEF): a state-of-the-science review

“…15 -17 Slightly higher post-treatment scores were observed for both drug and placebo conditions in the two Asian studies, 18,19 suggesting that Asian men might be slightly more susceptible to the nonspecific effects of treatment. However, the drugplacebo differences on Q3, Q4, and the EF domain were highly similar to those observed in both the European 16,17 and US 15 studies. Strong correlations were noted with other measures of treatment outcome (event logs, global efficacy ratings) in all five studies.…”

“…16,17 The first study 16 was conducted in six countries (Denmark, Ireland, Italy, Norway, Sweden, UK). In this study, 514 patients with ED of mixed etiologies were randomly assigned to 12 weeks of treatment with placebo or with a fixed dose of 25, 50 or 100 mg of sildenafil.…”

“…In the second study, 17 conducted in five European countries (Belgium, France, Germany, Netherlands, UK), 315 patients with ED of mixed etiologies were randomly assigned to flexible-dose sildenafil or placebo for 26 weeks. Mean scores of 1.9 for Q3 and 1.6 for Q4 at baseline increased, respectively, to 3.7 and 3.6 following 26 weeks of treatment with sildenafil (vs corresponding scores of 2.2 and 2.1 with placebo).…”

Cross-cultural adaptation and validation of the English version of the International Index of Erectile Function (IIEF) for use in Malaysia

“…Similarly, the mean change in score in the EF domain among responders (sensitivity) was 12.8 for the English IIEF, 6 while it was only 6.0 for the Malay IIEF. Interestingly, the mean change in EF domain scores observed in trials of sildenafil 3,11 conducted in Asia was about 11, which was similar to those observed in US 12 and European 13 trials. On that basis, a recent review of IIEF 4 suggests that the IIEF (or at least its EF domain) was a robust measure in different countries and cultures.…”

A meta-regression analysis of treatment effect modifiers in trials with flexible-dose oral sildenafil for erectile dysfunction in broad-spectrum populations

“…Of them, a total of 13 trials fulfilled all inclusion criteria and were included in the meta-regression analysis. [23][24][25][26][27][28][29][30][31][32][33][34][35] Characteristics of the included trials are presented in Table 1.…”