Abstract Introduction Oral phosphodiesterase type 5 (PDE5) inhibitors are accepted as first-line drug therapy and standard of care in males with erectile dysfunction (ED). However, their clinical efficacy is often hampered by pertinent issues such as the lack of spontaneity, onset of action and side effect profile. Objective This study evaluates the relative drug bioavailability, pharmacokinetics profile, and clinical safety of SPONTAN nasal spray (dose equivalent of Vardenafil 5 mg) compared to oral Vardenafil tablet (10 mg) in healthy adult males under fasting conditions and to determine if such an innovative intranasal delivery of Vardenafil potentially offers a more rapid onset of action and enhances sexual spontaneity for patients. Methods This Phase 1, open-label, single-dose, randomized, two-period, two-treatment crossover study involved 19 healthy male subjects. Subjects received SPONTAN Nasal Spray (5 mg) and Vardenafil tablet (10 mg) in a randomized sequence, with a 3-day washout period between treatments. Blood samples were collected at various time points up to 24 hours post-dose to determine vardenafil plasma concentrations. Pharmacokinetic parameters, including area under the curve (AUC), maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and half-life (T1/2), were assessed. The study also evaluated the safety and tolerability of both formulations. Results There was no significant difference in the patient demographics between the 2 groups. The pharmacokinetics study profile showed SPONTAN nasal spray to have a significantly faster Tmax (median time 12 mins) compared to Vardenafil tablet (median time 56 mins). The Cmax for the SPONTAN was 12.885 ng/ml, while the oral Vardenafil tablet was 16.737 ng/ml. The mean AUC0-t for the SPONTAN was (23.0968 hng/ml) compared to the tablet (42.1693 hng/ml). When adjusted for dose, SPONTAN showed higher drug bioavailability (AUC0-t/D ratio of 111.8%) compared to the Vardenafil tablet, despite the lower dose administered via the nasal route. The half-lives were similar between both treatments, with SPONTAN showing a mean T1/2 of 4.1486 hours compared to 4.2254 hours for the oral tablet. Both formulations were well-tolerated, with mild and transient treatment-emergent adverse events. The nasal spray was associated with a higher but transient incidence of local nasal irritations compared to oral tablets, which had higher gastrointestinal events. Conclusions SPONTAN nasal spray demonstrated faster drug absorption and higher dose-normalised bioavailability compared to the oral tablet, with a notably shorter Tmax. This shorter Tmax is expected to translate into a more rapid onset of action with a good safety profile and potentially offering greater drug flexibility in patients with ED who seek immediate treatment and sexual spontaneity. Disclosure Yes, this is sponsored by industry/sponsor: LTR Pharma Clarification: Industry initiated, executed and funded study
Chung et al. (Mon,) studied this question.