Effect of Varying Degrees of Renal Impairment on the Pharmacokinetics of Omecamtiv Mecarbil.

ABSTRACT:

Background and objective

Omecamtiv mecarbil is a novel selective cardiac myosin activator (myotrope) under investigation for the treatment of heart failure with reduced ejection fraction. The objective of this clinical study was to estimate the effect of varying degrees of renal impairment on the pharmacokinetics of omecamtiv mecarbil single dose (50 mg) under fasted conditions.

Methods

This phase I, open-label, non-randomized, parallel-group study evaluated the pharmacokinetics, safety, and tolerability of a single oral dose of omecamtiv mecarbil 50 mg in individuals with normal renal function or mild, moderate, and severe renal impairment, including end-stage renal disease requiring dialysis. Geometric least-squares mean ratios of maximum observed concentration (C_max) and area under the plasma concentration-time curve (AUC) and 90% confidence intervals were derived for comparisons of renal impairment vs normal renal function. Participants were monitored for adverse events.

Results

Thirty-one participants received treatment and completed the study. Geometric mean exposures were similar for participants with renal impairment (AUC_∞ range, 2550-3220 h*ng/mL; C_max range, 78.9-107 ng/mL) and participants with normal renal function (AUC_∞, 2790 h*ng/mL; C_max, 92.6 ng/mL), with geometric least-squares mean ratios of 85.2-125.9. Exposure was similar on dialysis vs non-dialysis days in participants with end-stage renal disease (AUC_0-24, 1650 vs 1700 h*ng/mL; C_max, 100.0 vs 107.0 ng/mL). Four participants (12.9%) reported four treatment-emergent adverse events. No deaths, treatment-emergent adverse events leading to discontinuation, or serious adverse events occurred.

Conclusions

Omecamtiv mecarbil pharmacokinetics were not meaningfully affected by renal function or hemodialysis, suggesting the same dosing strategy can be used in individuals with normal renal function or renal impairment. Oral administration of omecamtiv mecarbil was not associated with major tolerability findings. This study supports omecamtiv mecarbil for the treatment of heart failure in individuals with or without renal impairment.

SUBMITTER: Trivedi A 

PROVIDER: S-EPMC8332597 | biostudies-literature |

REPOSITORIES: biostudies-literature