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Background and Objectives <p>This phase I study was designed to evaluate the safety, tolerability, and pharmacokinetics of omecamtiv mecarbil with multiple oral doses at 25 mg twice daily, followed by titration to either 37.5 or 50&#xa0;mg twice daily in healthy Chinese participants.</p> Methods <p>Fifty healthy participants were enrolled and randomly assigned into three groups: Group A (20 subjects) received omecamtiv mecarbil 25&#xa0;mg in period 1 and either 37.5&#xa0;mg or 25 mg in period 2; Group B (20 subjects) received omecamtiv mecarbil 25 mg in period 1 and either 50 mg or 25&#xa0;mg in period 2; and Group C (10 subjects) received a placebo in both periods.</p> Results <p>The pharmacokinetics of omecamtiv mecarbil were well characterized in healthy Chinese participants. Across all subgroups, the mean terminal elimination half-life ranged from 18.3 to 21.3&#xa0;h. Mean accumulation ratios of area under the curve from time 0 to 12&#xa0;h ranged from 4.54 to 5.01 in period 1 and 2. The mean maximum observed concentration/plasma concentration before dosing ratios varied between 1.23 and 1.31 on days 8 and 34 across subgroups. No subjects experienced serious adverse events. The most frequently reported adverse events were an increased blood creatine kinase levels (12.5% of subjects in the omecamtiv mecarbil group, 10% in the placebo group), increased blood glucose levels (7.5%, 0), and bradycardia (10%, 0).</p> Conclusions <p>Omecamtiv mecarbil was well tolerated at the dose levels of 25–50 mg in healthy Chinese participants according to a pharmacokinetic-based titration scheme. Exposure of omecamtiv mecarbil was dose proportional, and no dose-related trends were observed in treatment-emergent adverse events.</p>

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Multiple-Dose Up-Titration Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Omecamtiv Mecarbil in Healthy Chinese Subjects

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • Xuening Li,
  • Hui Li,
  • Hongrong Xu,
  • Fei Yuan,
  • Hanjing Chen,
  • Chao Liu,
  • Mengjie Yang,
  • Jing Li,
  • Lei Sheng

摘要

Background and Objectives

This phase I study was designed to evaluate the safety, tolerability, and pharmacokinetics of omecamtiv mecarbil with multiple oral doses at 25 mg twice daily, followed by titration to either 37.5 or 50 mg twice daily in healthy Chinese participants.

Methods

Fifty healthy participants were enrolled and randomly assigned into three groups: Group A (20 subjects) received omecamtiv mecarbil 25 mg in period 1 and either 37.5 mg or 25 mg in period 2; Group B (20 subjects) received omecamtiv mecarbil 25 mg in period 1 and either 50 mg or 25 mg in period 2; and Group C (10 subjects) received a placebo in both periods.

Results

The pharmacokinetics of omecamtiv mecarbil were well characterized in healthy Chinese participants. Across all subgroups, the mean terminal elimination half-life ranged from 18.3 to 21.3 h. Mean accumulation ratios of area under the curve from time 0 to 12 h ranged from 4.54 to 5.01 in period 1 and 2. The mean maximum observed concentration/plasma concentration before dosing ratios varied between 1.23 and 1.31 on days 8 and 34 across subgroups. No subjects experienced serious adverse events. The most frequently reported adverse events were an increased blood creatine kinase levels (12.5% of subjects in the omecamtiv mecarbil group, 10% in the placebo group), increased blood glucose levels (7.5%, 0), and bradycardia (10%, 0).

Conclusions

Omecamtiv mecarbil was well tolerated at the dose levels of 25–50 mg in healthy Chinese participants according to a pharmacokinetic-based titration scheme. Exposure of omecamtiv mecarbil was dose proportional, and no dose-related trends were observed in treatment-emergent adverse events.