The Intra-Meatal Application of Tadalafil Cream Versus Oral Administration Efficacy and Safety: Results from a Randomized, Two-Administration Route, Cross-Over Clinical Trial.

Background: Tadalafil cream, a topically administered phosphodiesterase-5 inhibitor (PDE5), presents a potential alternative to oral PDE5 inhibitors like tadalafil for the treatment of erectile dysfunction (ED). This study evaluates the non-inferiority and potential superiority of tadalafil cream compared to oral tadalafil. Methods: This randomized controlled trial employed a cross-over design with two treatment periods of two weeks each, separated by a one-week washout phase. Thirty-five male participants aged 18-75 with diagnosed ED (International Index of Erectile Function-Erectile function: IIEF-EF score < 26) were randomized to receive either tadalafil cream or oral tadalafil. Tadalafil cream was applied topically, while tadalafil was taken orally. The primary endpoint was IIEF-EF, and secondary endpoints were measured using the International Index of Erectile Function (IIEF) domain scores. Adverse events and treatment preferences were also assessed. Results: Tadalafil cream showed a higher increase in sexual function across all IIEF domains compared to oral tadalafil. The lower bounds of the confidence interval [improvement: final-baseline scores between tadalafil cream and oral tadalafil 0.72 (95% CI -2.72-4.15)] were above the non-inferiority margin of -3.22, confirming tadalafil cream's non-inferiority in the erectile function domain. In the intercourse satisfaction domain, tadalafil cream was superior to oral tadalafil. At the end of the trial, 88.57% of participants preferred tadalafil cream (95% CI 73.26%-96.79%), a result significantly above the non-inferiority margin that indicated superiority (p < 0.001). No systemic adverse events were reported for tadalafil cream, and significant differences in dizziness, headache, nasal congestion, and erythema were observed between the two treatments. Conclusions: Tadalafil cream is a safe and effective treatment for erectile dysfunction, demonstrating non-inferiority and potential superiority over oral tadalafil, with a high patient preference. Its topical administration offers a promising alternative for patients, particularly those with cardiovascular diseases where oral PDE5 inhibitors are contraindicated or less well tolerated.