(128) The Pharmacodynamic Effects of Tunodafil Hydrochloride in Men with Erectile Dysfunction

Introduction Tunodafil hydrochloride is a novel, highly selective phosphodiesterase type 5 inhibitor developed for the treatment of erectile dysfunction (ED), and its clinical pharmacodynamic profile has not yet been characterized. Objective To assess the pharmacodynamic efficacy and safety of tunodafil (50 mg, 100 mg) during audiovisual sexual stimulation (AVSS) using RigiScan. Methods This multicenter, Phase I, randomized, double-blind, placebo-controlled, two-sequence, two-period crossover trial enrolled men aged 18–50 years with mild-to-moderate ED (International Index of Erectile Function-5 [IIEF-5] 8–21; duration ≥3 months). Subjects entered one of two dose cohorts (50 mg or 100 mg) and received tunodafil or placebo in Period 1, then crossed to the alternate treatment after a 7-day washout. RigiScan monitoring was performed at baseline and on each dosing day during standardized AVSS. The primary endpoint was duration of ≥60% penile rigidity at the tip and base. Secondary endpoints included time to ≥60% penile rigidity, maximum penile rigidity, percent increase in penile tumescence, and the proportion achieving Erection Hardness Score (EHS) ≥III. Safety was monitored throughout. Results Eighty men were randomized, and seventy-nine were included in the pharmacodynamic analysis set. Compared with placebo, tunodafil significantly prolonged the duration of ≥60% penile rigidity at the base and tip across both doses (all P<0.05). Mean (±SD) durations were 15.84 ± 20.997 min (50 mg) and 18.34 ± 20.507 min (100 mg) at the base, and 12.05 ± 15.832 min (50 mg) and 12.10 ± 18.495 min (100 mg) at the tip. Geometric mean ratios (tunodafil: placebo) for the duration of ≥60% penile rigidity were 5.71 (95% CI: 3.21-10.18) and 3.00 (1.29-7.00) at the tip and 2.44 (1.46-4.06) and 3.22 (1.76-5.90) at the base for the 50 mg and 100 mg doses, respectively. The 50 mg dose significantly shortened time to ≥60% rigidity and increased maximum rigidity at both the penile base and tip versus placebo (all P<0.05), with a similar trend observed at 100 mg. Percent increases in penile tumescence (from baseline) were also greater than placebo at both the base and tip for each dose (all P < 0.05). The proportion achieving EHS ≥III increased by 17.1 and 28.2 percentage points with 50 mg and 100 mg, respectively, versus placebo. No serious adverse events were reported. Conclusions Tunodafil showed robust pharmacodynamic activity and good tolerability under AVSS, supporting its further development as an on-demand therapeutic option for ED. Registered at the Chinese Clinical Trial Registry (ChiCTR): CTR20211282. Disclosure Yes, this is sponsored by industry/sponsor: Yangtze River Pharmaceutical Group Co, Ltd., Taizhou, China Clarification: Industry initiated, executed and funded study