The aim of this study was to assess the effect of volanesorsen on the corrected QT (QTc) interval. This thorough QT study enrolled 52 healthy male and female subjects who were randomized at a single site in a four-way crossover study. Subjects were randomly assigned to 1 of 12 treatment sequences and crossed over into four treatment periods over the course of which each subject was to receive a single therapeutic dose of volanesorsen as a 300 mg subcutaneous (SC) injection, a single supratherapeutic dose of volanesorsen as 300 mg intravenous (IV) infusion, a single oral (PO) dose of moxifloxacin (positive control), and placebo dose. The study demonstrated that volanesorsen 300 mg SC and 300 mg IV did not have a clinically relevant effect on ΔΔQTcF exceeding 10 ms. The largest mean effect at any postdose time point was 3.0 ms (90% confidence interval [CI]: 0.8–5.2) after SC dosing and 1.8 ms (90% CI −0.4 to 4.0) after IV dosing. Volanesorsen, at the studied therapeutic and supratherapeutic doses, does not have a clinically meaningful effect on the QTc.

中文翻译：

---

Volanesorsen 是一种靶向 APOC3 mRNA 的 2'-O-甲氧基乙基修饰反义寡核苷酸，不会影响健康志愿者的 QTc 间隔。

本研究的目的是评估 volanesorsen 对校正 QT (QTc) 间期的影响。这项全面的 QT 研究招募了 52 名健康男性和女性受试者，他们在一个四向交叉研究中随机分配到一个地点。受试者被随机分配到 12 个治疗序列中的 1 个，并跨入四个治疗期，在此期间，每个受试者接受单次治疗剂量的 volanesorsen 300 mg 皮下 (SC) 注射，单次超治疗剂量的 volanesorsen 为300 mg 静脉内 (IV) 输注、单次口服 (PO) 莫西沙星剂量（阳性对照）和安慰剂剂量。该研究表明，volanesorsen 300 mg SC 和 300 mg IV 对超过 10 ms 的 ΔΔQTcF 没有临床相关影响。在任何给药后时间点的最大平均效应为 3。SC 给药后 0 毫秒（90% 置信区间 [CI]：0.8-5.2），IV 给药后 1.8 毫秒（90% CI -0.4 至 4.0）。Volanesorsen，在研究的治疗和超治疗剂量下，对 QTc 没有临床意义的影响。