An open-label, single-dose, randomized, parallel-group study of the safety and relative bioavailability of topical sildenafil cream vs oral sildenafil in healthy male adults.

Introduction: Oral phosphodiesterase-5 (PDE5) inhibitors are commonly prescribed for erectile dysfunction (ED), but have limiting side effects, particularly for men with serious cardiovascular disease. Topical sildenafil cream was developed based on the hypothesis that local genital application would result in less systemic exposure and fewer side effects compared to oral sildenafil citrate. The objective of this study was to describe the systemic pharmacokinetics (PK) and safety of topical sildenafil cream 3.6% in healthy men, applied to the penis with and without male condom use, compared to oral sildenafil. Methods: Phase 1, open-label, single-dose, randomized, parallel-group design. Participants were randomized 1:1:1:1:1 to 36 mg of sildenafil in 1 g of cream or 71 mg of sildenafil in 2 g of cream self-applied to the penile skin with or without male condom use vs a 50 mg oral dose of sildenafil. Blood and orthostatic vital signs were taken prior to dosing and up to 32 hours post dosing. Safety was assessed by treatment emergent adverse events (TEAEs) and physical exam. Single dose PK parameters for plasma sildenafil and its active metabolite, N-desmethyl sildenafil were calculated. Results: Sixty-two men received study medication. All TEAEs ( Discussion: This safety and PK study provides early data on the comparison of Sildenafil cream topical dosing to the oral dosing referent. Topically applied Sildenafil Cream was safe and well tolerated by healthy men. Topical sildenafil cream use was associated with lower systemic exposure compared to oral sildenafil use.