Introduction

AMG 986 is a first-in-class, novel apelin receptor small molecule agonist initially developed for the treatment of heart failure (HF). The safety and pharmacokinetics (PK) of AMG 986 in participants with renal impairment (RI) remains unknown.

Methods

This phase 1 study compared the safety and PK of AMG 986 200 mg in six participants with severe RI (estimated glomerular filtration rate [eGFR] 15–29 mL/min/1.73 m²) versus six participants with normal renal function (eGFR ≥ 90 mL/min/1.73 m²).

Results

Following a single oral dose of AMG 986 200 mg on day 1, the maximum observed concentration increased 1.41-fold (90% confidence interval [CI] 0.88–2.27) and the area under the curve from time zero to infinity increased 1.23-fold (90% CI 0.73–2.06) in participants with severe RI versus normal renal function. AMG 986 had an acceptable safety profile; all adverse events were mild in severity.

Conclusions

The results of this study support the enrollment of HF patients with RI to clinical trials of AMG 986 without the need for dose adjustments.

Trial Registration Number

NCT03318809 (registered: October 24, 2017).

中文翻译：

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严重肾功能不全对 AMG 986 的安全性、耐受性和药代动力学的影响

介绍

AMG 986 是一种一流的新型 apelin 受体小分子激动剂，最初开发用于治疗心力衰竭 (HF)。AMG 986 在肾功能不全 (RI) 参与者中的安全性和药代动力学 (PK) 仍然未知。

方法

这项 1 期研究比较了 AMG 986 200 mg 在六名患有严重 RI（估计肾小球滤过率 [eGFR] 15–29 mL/min/1.73 m ²）的参与者与六名肾功能正常的参与者（eGFR ≥ 90毫升/分钟/1.73 米² )。

结果

在第 1 天单次口服 AMG 986 200 mg 后，观察到的最大浓度增加了 1.41 倍（90% 置信区间 [CI] 0.88-2.27），从零时间到无穷大的曲线下面积增加了 1.23 倍（ 90% CI 0.73–2.06）在患有严重 RI 与正常肾功能的参与者中。AMG 986 具有可接受的安全特性；所有不良事件的严重程度都是轻微的。

结论

该研究的结果支持将 RI 的 HF 患者纳入 AMG 986 的临床试验，而无需调整剂量。

试用注册号

NCT03318809（注册日期：2017 年 10 月 24 日）。