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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01737866
• Other study ID #: 20080676
• Status: Completed
• Phase: Phase 1
• Start date: November 2012
• Est. completion date: May 2013

Study information

• Verified date: July 2021
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: May 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Renal Insufficiency

Intervention

Drug:
• AMG 423
omecamtiv mecarbil

Locations

Country	Name	City	State
United States	Research Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AMG 423 Pharmacokinetic Parameters	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).	Twenty time points, up to eight days
Secondary	Other Total AMG 423 PK Parameters	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;	Twenty time points, up to eight days
Secondary	AMG 423 Dialysis Clearance	AMG 423 dialysis clearance (CLd) for ESRD subjects in Part A;	Hours 4, 5, 6, 7 & 8 post-dose
Secondary	AMG 423 Metabolites	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.	Twenty time points, up to eight days
Secondary	Safety	Secondary safety endpoints are subject incidence of adverse events and clinically significant changes in vital signs, physical examinations, clinical laboratory tests and ECGs.	Up to 46 days, including a 28 day screening period

External Links

•   AmgenTrials clinical trials website