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

Phase 1

Completed

• Conditions: Heart Failure
• Interventions: Drug: AMG 423

• Registration Number: NCT01737866
• Lead Sponsor: Cytokinetics

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2012-10-16
• Study Start: 2012-11
• Study First Submitted QC: 2012-11-28
• Study First Posted: 2012-11-30
• Primary Completion: 2013-01
• Study Completion: 2013-05
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-25
• Last Update Posted: 2021-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 1	AMG 423	End Stage Renal Diseas (ESRD) requiring hemodialysis
Group 2	AMG 423	Normal renal function (eGFR \>or = 80mL/min/1.73m\^2)
Group 3	AMG 423	Mild decrease in GFR (eGFR 60-79 mL/min/1.73m\^2)
Group 4	AMG 423	Moderate decrease in GFR (eGFR 30-59 mL/min/1.73m\^2)
Group 6	AMG 423	Normal renal function (eGFR \>or = 80mL/min/1.73m\^2)
Group 5	AMG 423	Severe decrease in GFR (eGFR 15-29 mL/min/1.73m\^2)

Primary Outcome Measures

Name	Time	Method
AMG 423 Pharmacokinetic Parameters	Twenty time points, up to eight days	Part A and Part B: Total AMG 423 pharmacokinetic parameters including area under the plasma concentration time curve (AUC) from time 0 to the time of the last quantifiable sample (AUC0-t) and maximum observed plasma concentration after dosing (Cmax).

Secondary Outcome Measures

Name	Time	Method
Other Total AMG 423 PK Parameters	Twenty time points, up to eight days	Total AMG 423 pharmacokinetic parameters including but not limited to terminal phase half life (t1/2) and time of maximum AMG 423 plasma concentration (tmax), AUC from time 0 to infinity (AUCinf) and apparent plasma clearance (CL/F) for Part A and Part B;
AMG 423 Dialysis Clearance	Hours 4, 5, 6, 7 & 8 post-dose	AMG 423 dialysis clearance (CLd) for ESRD subjects in Part A;
AMG 423 Metabolites	Twenty time points, up to eight days	AMG 423 metabolites (M3 and M4) pharmacokinetic parameters including but not limited to AUC0-t, AUCinf, AUC metabolite to parent ratios, Cmax, tmax and t1/2, if appropriate.
Safety	Up to 46 days, including a 28 day screening period	Secondary safety endpoints are subject incidence of adverse events and clinically significant changes in vital signs, physical examinations, clinical laboratory tests and ECGs.

Trial Locations

Locations (1)

Research Site; 🇺🇸 Orlando, Florida, United States