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

July 25, 2021 updated by: Cytokinetics

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32809
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AMG 423 Pharmacokinetic Parameters
Time Frame: 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).
Twenty time points, up to eight days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Other Total AMG 423 PK Parameters
Time Frame: 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;
Twenty time points, up to eight days
AMG 423 Dialysis Clearance
Time Frame: Hours 4, 5, 6, 7 & 8 post-dose
AMG 423 dialysis clearance (CLd) for ESRD subjects in Part A;
Hours 4, 5, 6, 7 & 8 post-dose
AMG 423 Metabolites
Time Frame: 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.
Twenty time points, up to eight days
Safety
Time Frame: 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.
Up to 46 days, including a 28 day screening period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cytokinetics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

October 16, 2012

First Submitted That Met QC Criteria

November 28, 2012

First Posted (Estimate)

November 30, 2012

Study Record Updates

Last Update Posted (Actual)

July 30, 2021

Last Update Submitted That Met QC Criteria

July 25, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20080676

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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