A phase II, single-blind, randomized, crossover evaluation of the safety and efficacy of avanafil using visual sexual stimulation in patients with mild to moderate erectile dysfunction
Article first published online: 12 JUL 2012
© 2012 BJU International
Volume 111, Issue 1, pages 137–147, January 2013
How to Cite
Hellstrom, W. J.G., Freier, M. T., Serefoglu, E. C., Lewis, R. W., DiDonato, K. and Peterson, C. A. (2013), A phase II, single-blind, randomized, crossover evaluation of the safety and efficacy of avanafil using visual sexual stimulation in patients with mild to moderate erectile dysfunction. BJU International, 111: 137–147. doi: 10.1111/j.1464-410X.2012.11267.x
- Issue published online: 20 DEC 2012
- Article first published online: 12 JUL 2012
- VIVUS, Inc
- erectile dysfunction;
- oral phosphodiesterase type 5 inhibitor;
- phase II study
What's known on the subject? and What does the study add?
- Phosphoesterase type 5 inhibitors (PDE5is) are considered standard-of-care for the treatment of men with erectile dysfunction. Recommended administration of currently used PDE5is are between 60- to 120-minutes before sexual activity. RigiScan® monitoring has been validated in previous clinical studies of PDE5 inhibitors.
- Using a highly objective measure of sexual function (RigiScan monitoring), data show that the onset of action of avanafil was rapid. Response to treatment with avanafil was associated most frequently with the earliest time interval tested (20–40 minutes after dosing), compared with sildenafil 50 mg (100 to 120 minutes after dosing). However, avanafil treatments showed some degree of efficacy across all time intervals tested (including 60–80 minutes and 100–120 minutes post-dosing). These results were consistent with data from phase 3 trials which showed a rapid onset of action with avanafil (as early as 15 minutes) and a long duration of effect (up to 6 hours in some patients). Safety results were consistent with those reported in phase 3 trials, and showed that avanafil was well tolerated and adverse events were generally low and mild in severity.
- To evaluate the safety, efficacy and time course of three doses of avanafil (50 mg, 100 mg and 200 mg) compared with sildenafil 50 mg or placebo, given in conjunction with visual sexual stimulation (VSS) videos in men with mild to moderate erectile dysfunction (ED).
Patients and Methods
- Male patients, 35–70 years of age, with mild to moderate ED of ≥6 months duration, were included in the study.
- During the course of the study, each patient received placebo, active control (sildenafil 50 mg), and one dose of avanafil (50 mg, 100 mg or 200 mg), all administered in random order at least 72 h apart.
- RigiScan® (Dacomed Corp., Minneapolis, MN, USA) monitoring was used in conjunction with 20-min VSS videos (20, 60, and 100 min after dosing) to determine the duration of and time to ≥60% penile rigidity, maximum rigidity, tumescent activity units (TAUs), rigidity activity units (RAUs), and responses to the five-point Erection Assessment Scale.
- Safety assessments included adverse events (AEs), vital sign changes in response to dosing, laboratory results (complete blood counts, chemistry panel, prostate-specific antigen, serum testosterone, prothrombin time and urine analysis) and physical examination findings.
- Eighty-three patients were randomized and received at least one dose of study medication; 82 patients completed the study.
- Peak response to avanafil occurred in the early interval (20–40 min after dosing), while peak response to sildenafil occurred either in the middle (60–80 min) or late (100–120 min) intervals after dosing.
- Results were qualitatively similar for all other efficacy endpoints.
- During the 20–40-min interval, the majority of values for TAUs and RAUs with the avanafil 50-mg, 100-mg and 200-mg treatments were significantly superior to placebo (P < 0.05).
- Avanafil treatment was generally well tolerated; facial flushing (7–15%) was the most commonly observed AE, and no visual disturbances were reported.
- A favourable safety profile and improvement in sexual function, coupled with rapid onset of action and durability of effect, make avanafil an attractive option for males with ED, especially in the setting of on-demand treatment.