Back to resultsPharmacokinetics Study of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMG 423
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Heart, Failure, Renal, Insufficiency, Cardiac, Kidney, Hemodialysis, Impairment, omecamtiv mecarbil, cardiac myosin activator, CK-1827452
Eligibility 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
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Group 1
Group 2
Group 3
Group 4
Group 5
Group 6
Arm Description
End Stage Renal Diseas (ESRD) requiring hemodialysis
Normal renal function (eGFR >or = 80mL/min/1.73m^2)
Mild decrease in GFR (eGFR 60-79 mL/min/1.73m^2)
Moderate decrease in GFR (eGFR 30-59 mL/min/1.73m^2)
Severe decrease in GFR (eGFR 15-29 mL/min/1.73m^2)
Normal renal function (eGFR >or = 80mL/min/1.73m^2)
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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;
AMG 423 Dialysis Clearance
AMG 423 dialysis clearance (CLd) for ESRD subjects in Part A;
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.
Safety
Secondary safety endpoints are subject incidence of adverse events and clinically significant changes in vital signs, physical examinations, clinical laboratory tests and ECGs.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01737866
Brief Title
Pharmacokinetics Study of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytokinetics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Heart, Failure, Renal, Insufficiency, Cardiac, Kidney, Hemodialysis, Impairment, omecamtiv mecarbil, cardiac myosin activator, CK-1827452
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
End Stage Renal Diseas (ESRD) requiring hemodialysis
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Normal renal function (eGFR >or = 80mL/min/1.73m^2)
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Mild decrease in GFR (eGFR 60-79 mL/min/1.73m^2)
Arm Title
Group 4
Arm Type
Experimental
Arm Description
Moderate decrease in GFR (eGFR 30-59 mL/min/1.73m^2)
Arm Title
Group 5
Arm Type
Experimental
Arm Description
Severe decrease in GFR (eGFR 15-29 mL/min/1.73m^2)
Arm Title
Group 6
Arm Type
Experimental
Arm Description
Normal renal function (eGFR >or = 80mL/min/1.73m^2)
Intervention Type
Drug
Intervention Name(s)
AMG 423
Intervention Description
omecamtiv mecarbil
Primary Outcome Measure Information:
Title
AMG 423 Pharmacokinetic Parameters
Description
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).
Time Frame
Twenty time points, up to eight days
Secondary Outcome Measure Information:
Title
Other Total AMG 423 PK Parameters
Description
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;
Time Frame
Twenty time points, up to eight days
Title
AMG 423 Dialysis Clearance
Description
AMG 423 dialysis clearance (CLd) for ESRD subjects in Part A;
Time Frame
Hours 4, 5, 6, 7 & 8 post-dose
Title
AMG 423 Metabolites
Description
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.
Time Frame
Twenty time points, up to eight days
Title
Safety
Description
Secondary safety endpoints are subject incidence of adverse events and clinically significant changes in vital signs, physical examinations, clinical laboratory tests and ECGs.
Time Frame
Up to 46 days, including a 28 day screening period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Pharmacokinetics Study of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency
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