Elmore Kimberly, DeVincenzo John, Rhodin Michael H J, Rottinghaus Scott T, Ahmad Alaa
Enanta Pharmaceuticals, Inc., Watertown, Massachusetts, USA.
Clin Transl Sci. 2025 May;18(5):e70231. doi: 10.1111/cts.70231.
Respiratory syncytial virus (RSV) remains a significant health concern, particularly for vulnerable populations. Despite preventive strategies, there remains a need for effective antiviral treatments. EDP-323 is a first-in-class, potent oral selective non-nucleoside inhibitor of the large protein (L polymerase) of RSV under investigation for the treatment of RSV infection. This phase 1, randomized, double-blind, placebo-controlled study evaluated the safety and pharmacokinetics of EDP-323. This study included fasted single ascending dose (SAD; EDP-323 50/100/200/400/600/800 mg doses, 3:1 to placebo), fed multiple ascending dose (MAD; EDP-323200/400/600/800 mg doses, 3:1 to placebo), and food effect (EDP-323200 mg dose, 4:1 to placebo) cohorts in healthy adult participants. Key objectives were to assess the safety, tolerability, and pharmacokinetic (PK) profile of EDP-323 in plasma and urine, and to evaluate the effect of food intake on its pharmacokinetics. Among 82 randomized participants (SAD, n = 50; MAD, n = 32), EDP-323 was well tolerated up to the highest tested dose (800 mg once daily for 7 days). Adverse events (AEs) were reported in 14.6% of total participants, with the majority being mild and deemed unlikely related to the study drug. Headache was the most frequent AE (n = 3). PK analysis showed that EDP-323 was rapidly absorbed (T = 3.0-5.0 h), with exposures increasing with ascending dose. The half-life of EDP-323 (t = 10.8-16.6 h) supported once-daily dosing, and no food effect was observed. EDP-323 demonstrated a favorable safety and PK profile, supporting its potential as a once-daily oral treatment for RSV.
呼吸道合胞病毒（RSV）仍然是一个重大的健康问题，尤其是对弱势群体而言。尽管有预防策略，但仍需要有效的抗病毒治疗方法。EDP-323是一种一流的、强效的口服选择性非核苷类呼吸道合胞病毒大蛋白（L聚合酶）抑制剂，正在进行治疗呼吸道合胞病毒感染的研究。这项1期随机、双盲、安慰剂对照研究评估了EDP-323的安全性和药代动力学。该研究纳入了健康成年受试者的空腹单次递增剂量（SAD；EDP-323剂量为50/100/200/400/600/800毫克，与安慰剂的比例为3:1）、进食多次递增剂量（MAD；EDP-323剂量为200/400/600/800毫克，与安慰剂的比例为3:1）以及食物影响（EDP-323剂量为200毫克，与安慰剂的比例为4:1）队列。主要目标是评估EDP-323在血浆和尿液中的安全性、耐受性和药代动力学（PK）特征，并评估食物摄入对其药代动力学的影响。在82名随机分组的受试者中（SAD组n = 50；MAD组n = 32），EDP-323在最高测试剂量（每日一次，800毫克，共7天）下耐受性良好。14.6%的受试者报告了不良事件（AE），大多数为轻度，且被认为不太可能与研究药物有关。头痛是最常见的不良事件（n = 3）。药代动力学分析表明，EDP-323吸收迅速（T = 3.0 - 5.0小时），暴露量随剂量增加而增加。EDP-323的半衰期（t = 10.8 - 16.6小时）支持每日一次给药，且未观察到食物影响。EDP-323显示出良好的安全性和药代动力学特征，支持其作为呼吸道合胞病毒每日一次口服治疗药物的潜力。
