Department of Drug Clinical Trial Center, Peking University Third Hospital, Huayuan North Road No. 49, Haidian, Beijing, China.
Department of Cardiology and Institute of Vascular Medicine, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University Third Hospital, Beijing, China.
Clin Drug Investig. 2023 Jul;43(7):503-515. doi: 10.1007/s40261-023-01277-4. Epub 2023 Jun 28.
PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals.
Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed.
Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration-time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials.
PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.
PSD502 是一种用于治疗早泄的定量喷雾器。两项试验旨在评估 PSD502 在健康中国男性和女性个体中的安全性和药代动力学。
两项 I 期、随机、双盲、安慰剂对照试验分别在男性（试验 1）和女性（试验 2）中进行。参与者按照 3:1 的比例随机分配接受 PSD502（每个喷雾 7.5 毫克利多卡因和 2.5 毫克丙胺卡因）或安慰剂。对于男性个体，每天在龟头处应用单剂量（三喷），连续 21 天，但第 7 天和第 14 天除外，每 4 小时喷三喷，共三剂。对于女性个体，每天阴道应用两喷，宫颈应用一喷。主要终点是安全性。还进行了药代动力学分析。
共招募了 24 名男性和 24 名女性个体。在 PSD502 组中，分别有 38.9%（7/18）的男性和 66.7%（12/18）的女性出现治疗后出现不良事件，而安慰剂组分别为 50.0%（3/6）。两项试验均报告有 50.0%（3/6）的治疗后出现不良事件。没有发生任何≥3 级的治疗后出现不良事件、严重不良事件或导致提前退出或停药的治疗后出现不良事件。连续应用后，利多卡因和丙胺卡因在两项试验中均迅速清除。血浆浓度表现出高度的个体间变异性。活性成分的最大血浆浓度远低于预期的最小毒性浓度。代谢物的血浆浓度-时间曲线下面积均≤母体药物的 20%。两项试验均未观察到明显的蓄积。
PSD502 在健康的中国男性和女性个体中耐受性良好，血浆浓度较低。
