Effect of Severe Renal Impairment on the Safety, Tolerability, and Pharmacokinetics of AMG 986

Ashit Trivedi, Omar Mather, Silvia Vega, Mary Ann Simiens, Jennifer Hellawell, Edward Lee, Ashit Trivedi, Omar Mather, Silvia Vega, Mary Ann Simiens, Jennifer Hellawell, Edward Lee

Abstract

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).

Conflict of interest statement

AT, OM, SV, MAS, JH, and EL are employees and shareholders of Amgen Inc.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Chemical structure of AMG 986.
Fig. 2
Fig. 2
Mean (SD) plasma concentration–time profiles for AMG 986 200 mg administered orally to participants with severe RI and normal renal function (inset = time 0 to 48 hours). LLOQ lower limit of quantitation, RI renal impairment, SD standard deviation

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