背景:MK-0616是一种用于治疗高胆固醇血症的口服PCSK9大环肽抑制剂。
目标:这个2b阶段,随机化,双盲,安慰剂对照,多中心试验(NCT05261126)旨在评估MK-0616在高胆固醇血症参与者中的疗效和安全性.
方法:这项研究计划包括375名具有广泛ASCVD风险的成年参与者。参与者被随机分配(1:1:1:1:1:1比例)至MK-0616(6、12、18或30mgQD)或匹配的安慰剂。主要终点包括第8周时LDL-C相对于基线的百分比变化以及因AE而发生不良事件(AE)和研究干预中止的参与者比例;在治疗期后对参与者的AE进行了另外8周的监测。
结果:在随机分组的381名参与者中,49%是女性,中位年龄为62岁。在380名接受治疗的参与者中,MK-0616的所有剂量均显示出从基线到第8周LDL-C的LS平均百分比变化与统计学上的显着差异(p<0.001)安慰剂:-41.2%(6mg),-55.7%(12毫克),-59.1%(18毫克),和-60.9%(30mg)。在MK-0616组(39.5%至43.4%)的参与者中,与安慰剂(44.0%)的比例相似。在任何治疗组中,有2名或更少的参与者因AE而中断。
结论:MK-0616具有统计学意义和鲁棒性,在第8周时,剂量依赖性安慰剂校正LDL-C较基线降低高达60.9%,且在治疗8周和额外8周随访期间耐受性良好.
MK-0616 is an oral macrocyclic peptide inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) in development for the treatment of hypercholesterolemia.
This Phase 2b, randomized, double-blind, placebo-controlled, multicenter trial aimed to evaluate the efficacy and safety of MK-0616 in participants with hypercholesterolemia.
This trial was planned to include 375 adult participants with a wide range of atherosclerotic cardiovascular disease risk. Participants were assigned randomly (1:1:1:1:1 ratio) to MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo. The primary endpoints included percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 8 and the proportion of participants with adverse events (AEs) and study intervention discontinuations due to AEs; participants were monitored for AEs for an additional 8 weeks after the 8-week treatment period.
Of the 381 participants randomized, 49% were female, and the median age was 62 years. Among 380 treated participants, all doses of MK-0616 demonstrated statistically significant (P < 0.001) differences in least squares mean percentage change in LDL-C from baseline to Week 8 vs placebo: -41.2% (6 mg), -55.7% (12 mg), -59.1% (18 mg), and -60.9% (30 mg). AEs occurred in a similar proportion of participants in the MK-0616 arms (39.5% to 43.4%) as placebo (44.0%). Discontinuations due to AEs occurred in 2 or fewer participants in any treatment group.
MK-0616 demonstrated statistically significant and robust, dose-dependent placebo-adjusted reductions in LDL-C at Week 8 of up to 60.9% from baseline and was well tolerated during 8 weeks of treatment and an additional 8 weeks of follow-up. (A Study of the Efficacy and Safety of MK-0616 [Oral PCSK9 Inhibitor] in Adults With Hypercholesterolemia [MK-0616-008]; NCT05261126).