Amgen Inc., Thousand Oaks, California, USA.
Covance Inc., Madison, Wisconsin, USA.
Biopharm Drug Dispos. 2021 Jul;42(7):319-328. doi: 10.1002/bdd.2293. Epub 2021 Jun 18.
Omecamtiv mecarbil (OM) is a cardiac myosin activator in clinical development for the treatment of heart failure. The effect of food on the pharmacokinetics (PK) of 25, 37.5, and 50 mg strength modified release (MR) tablets and the bioequivalence of two 25 mg tablets versus one 50 mg MR tablet were evaluated in two open-label, randomized, cross-over studies in healthy subjects. Subjects received two 25 mg tablets or one 50 mg OM MR tablet under fed or fasted states in Study 1 (n = 39), and single oral doses of 25 and 37.5 mg OM MR tablets and to assess its relative bioavailability to the 25 mg MR tablet, a 25 mg oral solution under fed or fasted states in Study 2 (n = 34). The area under the concentration-time curve (AUC) and the maximum observed concentration (C ) of 25, 37.5, or 50 mg OM MR tablets were approximately 13%-22% higher and 31%-40% higher, respectively, when taken with food. The two 25 mg and one 50 mg OM MR tablets were bioequivalent (90% confidence intervals) of the geometric mean ratios for C and AUC of OM were within 0.8-1.25 under the fasted or fed state. OM was well tolerated and all treatment-emergent events were mild in severity and resolved by the end of the study. In conclusion, these studies demonstrated that the effect of food on the PK of OM was minimal at all three studied strengths of the MR tablets, and two 25 mg MR tablets may be switched for one 50 mg MR tablet (EudraCT Number: 2019-003683-44).
奥马环巴（OM）是一种正在临床开发用于心力衰竭治疗的心肌肌球蛋白激活剂。在两项健康受试者的开放标签、随机交叉研究中评估了食物对 25、37.5 和 50mg 强度改良释放（MR）片剂的药代动力学（PK）的影响，以及两种 25mg 片剂与一种 50mg MR 片剂的生物等效性。在研究 1（n=39）中，受试者在进食或禁食状态下分别服用两种 25mg 片剂或一种 50mg OM MR 片剂，在研究 2（n=34）中，单次口服 25 和 37.5mg OM MR 片剂，并评估其相对于 25mg MR 片剂的相对生物利用度，在进食或禁食状态下口服 25mg 口服液。与禁食状态相比，当与食物一起服用时，25、37.5 或 50mg OM MR 片剂的 AUC 和 C 的 13%-22%和 31%-40%分别更高。两种 25mg 和一种 50mg OM MR 片剂在禁食或进食状态下的 OM 的 C 和 AUC 的几何均数比值均具有生物等效性（90%置信区间在 0.8-1.25 内）。OM 耐受性良好，所有治疗后出现的事件均为轻度，在研究结束时已解决。总之，这些研究表明，在所有三种研究强度的 MR 片剂中，食物对 OM 的 PK 影响很小，两种 25mg MR 片剂可转换为一种 50mg MR 片剂（EudraCT 编号：2019-003683-44）。
