Pharmacokinetics Study of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency

An Open-label, Single-dose Study of the Safety, Tolerability, and Pharmacokinetics of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency and Effect of Hemodialysis on AMG 423 Pharmacokinetics

A phase 1, open-label study in subjects with normal renal function and subjects with various degrees of renal insufficiency, including patients with end-stage renal disease (ESRD) requiring hemodialysis. The primary objective is to evaluate the single-dose PK of AMG 423 in subjects with various degrees of renal insufficiency, including patients with end-stage renal disease requiring hemodialysis.

This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.

Inclusion Criteria:

• Men or women ≥18 years of age
• Laboratory test values (clinical chemistry and hematology)within normal limits, (other than test values out of the normal range for subjects with CKD [groups 1 and 3 through 5]), or clinically acceptable to the investigator and sponsor at screening and day -3
• Free of any clinically significant disease or condition(s) (other than that consistent with CKD for subjects in groups 1 and 3 through 5) that require a physician's care and/or would interfere with the evaluations, procedures, or participation in the study per the investigator's discretion;

Exclusion Criteria:

• Subjects whose second MDRD eGFR result during the screening period is not within 10% of the first eGFR result
• Subjects who have received a functioning renal transplant within the past year
• Subjects with ESRD who do not have a functioning hemodialysis access
• Subjects with hemodynamic instability during hemodialysis
• Subjects whose renal insufficiency is due to active autoimmune renal disease
• Subjects with renal insufficiency or ESRD requiring hemodialysis and Troponin I > upper limit of normal (ULN) at screening or day -3
• Subjects with history of heart disease or unstable angina within the last 3 months
• Subjects with uncontrolled diabetes (Hb1Ac > 8%) and/or subjects who are able but unwilling to adhere to the required fasting intervals