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

This study has been completed.
Sponsor:
Collaborator:
Cytokinetics
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01737866
First received: October 16, 2012
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Heart Failure
Drug: AMG 423
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • AMG 423 Pharmacokinetic Parameters [ Time Frame: Twenty time points, up to eight days ] [ Designated as safety issue: No ]
    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:
  • Other Total AMG 423 PK Parameters [ Time Frame: Twenty time points, up to eight days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Hours 4, 5, 6, 7 & 8 post-dose ] [ Designated as safety issue: No ]
    AMG 423 dialysis clearance (CLd) for ESRD subjects in Part A;

  • AMG 423 Metabolites [ Time Frame: Twenty time points, up to eight days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 46 days, including a 28 day screening period ] [ Designated as safety issue: Yes ]
    Secondary safety endpoints are subject incidence of adverse events and clinically significant changes in vital signs, physical examinations, clinical laboratory tests and ECGs.


Enrollment: 13
Study Start Date: November 2012
Study Completion Date: May 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01737866

Locations
United States, Florida
Research Site
Orlando, Florida, United States, 32809
Sponsors and Collaborators
Amgen
Cytokinetics
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01737866     History of Changes
Other Study ID Numbers: 20080676
Study First Received: October 16, 2012
Last Updated: August 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Heart, Failure, Renal, Insufficiency, Cardiac, Kidney, Hemodialysis, Impairment, omecamtiv mecarbil, cardiac myosin activator, CK-1827452

Additional relevant MeSH terms:
Heart Failure
Renal Insufficiency
Heart Diseases
Cardiovascular Diseases
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on August 28, 2014