New York--Avanafil, an investigational, fast-acting phosphodiesterase type-5 inhibitor, has been successful in its first large-scale trial, Joel M. Kaufman, MD, reported at the Sexual Medical Society of North America annual meeting here.
The study, led by Dr. Kaufman, associate clinical professor of urology at the University of Colorado School of Medicine, Denver, was a phase II trial in the sequence of protocols needed to obtain FDA approval for drugs. Plans for a phase III trial, the last step in that sequence, are being made for 2006, according to VIVUS, Inc., which is developing the drug.
The effect of avanafil was seen within 30 minutes, and its half-life was 90 minutes, Dr. Kaufman reported.
The double-blind, placebo-controlled trial enrolled 284 men, 32 to 70 years of age with mild to moderate erectile dysfunction experienced for a median 66.7 months. Men in the active arm were assigned avanafil, 50 mg, 100 mg, 200 mg, or 300 mg, and were instructed to take it 30 minutes before initiating sexual activity. The duration of the trial was 12 weeks.
Of the men taking placebo, 60.5% achieved vaginal penetration. All four doses of avanafil significantly increased vaginal penetration when compared with placebo, and the rate for achieving vaginal penetration increased with dosage: 76.1 % with 50 mg, 79.2% with 100 mg, 79.8% with 200 mg, and 83.7% with 300 mg.
A more striking difference in effect between placebo and avanafil was demonstrated in the ability of the men to maintain erection long enough to successfully complete intercourse. Less than one-third of the placebo recipients (28.9%) were successful, while in the avanafil group, the success rate was dose-related: 53.4% for men taking 50 mg, 58.6% for men taking 100 mg, 62.1% for those taking 200 mg, and 64.3% for those taking 300 mg.
Side effects were minor. The most common was headache, the incidence of which increased with dosage, reported by 7% of men receiving the 50-mg dose, 12% of those in the 100-mg group, 13% of men taking the 200-mg dose, and 26% of those receiving the 300-mg dose.
Data on avanafil's half-life came from a study reported at this meeting by Craig Peterson, PhD, director of clinical research at VIVUS. In this study, serial blood samples were drawn over a 48-hour period from 15 healthy men given a single 200-mg dose. Administration of avanafil resulted in maximum blood levels at approximately 30 minutes, which corresponds to the drug's rapid onset of action, Dr. Peterson said. Plasma disappearance was rapid, with a half-life of between 1 and 1.5 hours.
An animal study, reported by Tanabe Research Laboratories in Japan, found that "avanafil is the most selective PDE-5 inhibitor" when tested against sildenafil citrate (Viagra), vardenafil (Levitra), and tadalafil (Cialis), the authors said.
VIVUS hopes to begin a phase III trial some time in 2006, the company said. The avanafil studies presented at the SMSNA meeting were sponsored by VIVUS.