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

Cytokinetics

Status and phase: Completed; Phase 1

Conditions: Heart Failure

Treatments: Drug: AMG 423

Study type: Interventional

Funder types: Industry

Identifiers

NCT01737866

20080676

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 13 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 6 patient groups

Group 1

Experimental group

Description:

End Stage Renal Diseas (ESRD) requiring hemodialysis

Treatment:

Drug: AMG 423

Group 2

Experimental group

Description:

Normal renal function (eGFR \>or = 80mL/min/1.73m\^2)

Treatment:

Drug: AMG 423

Group 3

Experimental group

Description:

Mild decrease in GFR (eGFR 60-79 mL/min/1.73m\^2)

Treatment:

Drug: AMG 423

Group 4

Experimental group

Description:

Moderate decrease in GFR (eGFR 30-59 mL/min/1.73m\^2)

Treatment:

Drug: AMG 423

Group 5

Experimental group

Description:

Severe decrease in GFR (eGFR 15-29 mL/min/1.73m\^2)

Treatment:

Drug: AMG 423

Group 6

Experimental group

Description:

Normal renal function (eGFR \>or = 80mL/min/1.73m\^2)

Treatment:

Drug: AMG 423