April 10, 2001
New York - Vardenafil, a phosphodiesterase-5 (PDE-5) inhibitor, has been shown to improve erections in up to 80% of men and increase their ability to complete sexual intercourse with ejaculation, according to a presentation at the XVI annual European Association of Urology (EAU) meeting in Geneva, Switzerland. The study was the first large-scale patient trial of vardenafil, which is made by Bayer.
"Vardenafil improved erectile function in these men, regardless of their age, cause, or severity of their problem. This improvement occurred even at the lowest dose of 5 mg," said Dr. Irwin Goldstein, Boston University School of Medicine, a co-author of the study and a member of the international Vardenafil Study Group. "There was another important finding as well," continued Goldstein. "In the overall study, vardenafil not only helped most men achieve erections, they also were able to sustain their erections and successfully complete intercourse."
The analyses involved 580 patients, aged 21-70 years, in stable heterosexual relationships, from 39 treatment centers in the United States, Belgium, France, Germany, the Netherlands, Poland, and South Africa. The patients had experienced difficulty with erectile function of organic, psychogenic, or mixed etiology for an average of 2.8 years. They were randomized into 4 groups and received vardenafil in 5 mg, 10 mg, 20 mg doses, or placebo on demand, but not more than once a day.
In subanalyses, effects of vardenafil were evaluated by patients' responses to 2 key questions of the International Index of Erectile Function (IIEF) questionnaire: the ability to penetrate (question 3 [Q3]) and the ability to maintain an erection during intercourse (question 4 [Q4]). The scoring was based on a 5-point scale, with one being the most severe.
Those with a baseline Q3 score of 1.0 (ie, with very little ability to penetrate) increased their score to a mean of 1.8 with placebo and to 3.0, 3.1, and 3.7 with 5 mg, 10 mg, and 20 mg of vardenafil, respectively. Those with a starting score of 4.0 on Q3 deteriorated to a mean score of 3.4 with placebo, but increased to a mean of 4.4, 4.7, or 4.4 for the same increasing doses of vardenafil.
For Q4, the results were similar. Those with a score of 1.0 (ie, with very little ability to maintain an erection and complete intercourse) increased their score to a mean of 2.0 with placebo and to scores of 3.3, 3.1, and 3.5 with increasing doses of vardenafil. Those with a relatively mild degree of severity starting with a score of 4.0 had a decreased mean of 3.6 on placebo, but reached a score of 4.0, 4.3, or 4.7 with increasing doses of vardenafil.
Having an organic or psychogenic etiology of erectile dysfunction did not influence the efficacy of vardenafil. The mean changes in score of Q3 for organic and psychogenic erectile dysfunction were: 0.3 and 0.3 for placebo, 1.2 and 1.4 for 5 mg, 1.5 and 1.1 for 10 mg, and 1.3 and 1.4 for 20 mg doses of vardenafil, respectively. Similar responses were seen for Q4.
The patients were divided into 4 age groups: younger than 45 years, 45-55 years, 55-65 years, and older than 65 years. For Q4, the mean increases in score for placebo-treated patients ranged between 0.2 and 0.8 in each age group. For vardenafil-treated patients, a statistically significant treatment effect was found for all doses with mean increases ranging between 0.8 and 1.9, but no one age group had a superior response to vardenafil.
"Our study also demonstrated that vardenafil was well tolerated, with few patients reporting any adverse events," Dr. Goldstein reported. The most frequent adverse events, whether related to the drug or not, were headache (7-15%), flushing (10-11%), rhinitis (3-7%), and dyspepsia (1-7%). The events were generally mild in intensity and related to dosage.
In preclinical studies,
the pro-erectile activity of vardenafil was greater than sildenafil at
equivalent dosing. In a separate study, vardenafil was found to be highly
selective at targeting the PDE-5 enzyme, which is believed to be responsible
for inducing erections. Vardenafil is now being evaluated in Phase III
trials to better understand if these characteristics will translate into
clinical benefits for patients. Results are expected for publication later
this year, with completion of the Food and Drug Administration (FDA) review
in the second half of 2002. Current estimates suggest that more than half
of all men in the United States older than 40 years experience some difficulty
with erectile function.
MedscapeWire is edited
by Deborah Flapan