1480 Onset of Action and Time to Efficacy of Avanafil, a Novel, Rapid-Onset Pde5 Inhibitor in Men With Mild to Severe Erectile Dysfunction Data From Phase 2 and Phase 3 Clinical Trials

Hellstrom, Wayne J.G.; Freier, Matthew T.; Şerefoğlu, Ege Can; Lewis, Ronald W.; Peterson, Craig A.; DiDonato, Karen; Day, Wesley W.

doi:10.1016/j.juro.2012.02.2002

Cited by 4 publications

(13 citation statements)

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“…Avanafil demonstrated even more impressive results in study TA‐301, which analysed success rates of sexual attempts made ≤ 15 min and > 6 h after dosage with avanafil. 66.7% and 69.4% of patients taking avanafil were successful, compared with 48.1% and 50.0% in the placebo group respectively for both (101).…”

Section: Pde5i Efficacy and Tolerabilitymentioning

confidence: 99%

PDE5 inhibitors: considerations for preference and long-term adherence

Smith

McCaslin

Gökçe

et al. 2013

International Journal of Clinical Practice

100

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Summary Introduction: Erectile dysfunction (ED) is a highly prevalent condition affecting nearly one in five men worldwide. The advent of phosphodiesterase type 5 inhibitors (PDE5i) has revolutionised the ED treatment landscape and provided effective, minimally invasive therapies to restore male sexual function. Materials and methods: A pubmed search was performed of all English language articles from 1996 to present reviewing PDE5i, including pharmacokinetics, efficacy profiles and comparisons, where available. Results: Currently available PDE5i in the United States include sildenafil, vardenafil, tadalafil and avanafil, each of which has unique side effect, pharmacokinetic and outcome profiles. Sildenafil is associated with increased rate of visual changes, vardenafil with QT prolongation and tadalafil with lower back pain. Avanafil and vardenafil orodispersible tablet rapidly achieve peak plasma concentration, which results in faster onset of action, whereas tadalafil exhibits the longest half‐life. First time response to PDE5i is approximately 60–70%, with no significant differences in efficacy noted among therapies. The literature does not clearly demonstrate a preference for one drug. High‐treatment success rates (89%) were reported when patients were prescribed all available PDE5i. Daily dosing with tadalafil is associated with improved erectile function (EF) over time. Finally, novel modes of patient–provider interaction, including internet‐based education, communication and prescribing, may also improve long‐term adherence. Conclusions: PDE5i represent first line therapy for ED with excellent overall efficacy and satisfactory side effect profiles. Enhanced communciation, coupled with increased knowledge of drug characteristics, comparative treatment regimens and optimal prescribing patterns, offer compelling tools to improve long‐term treatment success.

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Section: Pde5i Efficacy and Tolerabilitymentioning

confidence: 99%

PDE5 inhibitors: considerations for preference and long-term adherence

Smith

McCaslin

Gökçe

et al. 2013

International Journal of Clinical Practice

100

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“…In the phase III clinical trials, avanafil was also associated with a rapid onset of action and durability of effect . In some patients, there was a significant treatment response as early as 15 min after dosing, which may extend to 6 h. In study TA‐301, in males with mild to severe ED and without diabetes, after avanafil treatment, 66.7% and 69.4% of patients making sexual attempts within ≤15 min and >6 h were successful compared with 48.1% and 50% for placebo, respectively for both .…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2012

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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. Objective 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. Results 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). Avanafi...

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“…Avanafil is a highly selective inhibitor of PDE 5 , possessing a unique diaminopyrimidine derived chemical structure. 12-20 It is a competitive antagonist of cyclic guanosine monophosphate (cGMP) at the catalytic binding pocket of the phosphodiesterase enzyme. The inhibition of this enzyme allows for an increase in cGMP levels, resulting in a reduction in intracellular calcium.…”

Section: Pharmacologymentioning

confidence: 99%

“…12-20 However, its absorption can be affected if taken with a high-fat meal, delaying T max up to 1.25 hours and reducing maximum concentrations (C max ) by approximately 24% (100 mg) and 39% (200 mg) after administration. 12,20 Avanafil has a degree of protein binding that is independent of total drug concentrations, age, renal function, and hepatic function. It undergoes hepatic metabolism predominantly by the cytochrome P450 (CYP) 3A4 enzyme and to a minor extent the CYP2C isoform.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The terminal elimination half-life is 5 hours, with 62% excreted in the feces and 21% excreted in the urine. 12,13,20 No dosage adjustments are necessary based on renal function, hepatic function, age, or gender. Because of the lack of safety and efficacy data, avanafil should not be used in patients younger than 18 years though use in this population would not be anticipated.…”

Section: Pharmacokineticsmentioning

confidence: 99%

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