Heart FailurePhase 1NCT01737866
Pharmacokinetics Study of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency
A Phase 1 study testing AMG 423 in people with Heart Failure, run by Cytokinetics at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Heart Failure
- What is being tested?
- AMG 423
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to May 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- AMG 423
- Keywords
- Heart, Failure, Renal, Insufficiency, Cardiac, Kidney, Hemodialysis, Impairment, omecamtiv mecarbil, cardiac myosin activator, CK-1827452
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 423Drug
omecamtiv mecarbil
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | End Stage Renal Diseas (ESRD) requiring hemodialysis Receives: Drug: AMG 423 |
| Group 2 | Experimental | Normal renal function (eGFR >or = 80mL/min/1.73m^2) Receives: Drug: AMG 423 |
| Group 3 | Experimental | Mild decrease in GFR (eGFR 60-79 mL/min/1.73m^2) Receives: Drug: AMG 423 |
| Group 4 | Experimental | Moderate decrease in GFR (eGFR 30-59 mL/min/1.73m^2) Receives: Drug: AMG 423 |
| Group 5 | Experimental | Severe decrease in GFR (eGFR 15-29 mL/min/1.73m^2) Receives: Drug: AMG 423 |
| Group 6 | Experimental | Normal renal function (eGFR >or = 80mL/min/1.73m^2) Receives: Drug: AMG 423 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Twenty time points, up to eight days
Secondary outcomes (4)
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;
Measured: Twenty time points, up to eight days
AMG 423 Dialysis Clearance
AMG 423 dialysis clearance (CLd) for ESRD subjects in Part A;
Measured: Hours 4, 5, 6, 7 & 8 post-dose
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.
Measured: Twenty time points, up to eight days
Safety
Secondary safety endpoints are subject incidence of adverse events and clinically significant changes in vital signs, physical examinations, clinical laboratory tests and ECGs.
Measured: Up to 46 days, including a 28 day screening period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionJan 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01737866
- Sponsor's protocol ID
- 20080676
- Status last verified
- Jul 2021
- First submitted
- 16 Oct 2012
- Last updated
- 30 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01737866
- Acronym / sponsor ID
- 20080676
- Conditions
- Heart Failure
- Keywords
- Heart, Failure, Renal, Insufficiency, Cardiac, Kidney, Hemodialysis, Impairment, omecamtiv mecarbil, cardiac myosin activator, CK-1827452
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Study start
- Nov 2012
- Primary completion
- Jan 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 30 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: AMG 423End Stage Renal Diseas (ESRD) requiring hemodialysis |
| Group 2 | Experimental | Drug: AMG 423Normal renal function (eGFR >or = 80mL/min/1.73m^2) |
| Group 3 | Experimental | Drug: AMG 423Mild decrease in GFR (eGFR 60-79 mL/min/1.73m^2) |
| Group 4 | Experimental | Drug: AMG 423Moderate decrease in GFR (eGFR 30-59 mL/min/1.73m^2) |
| Group 5 | Experimental | Drug: AMG 423Severe decrease in GFR (eGFR 15-29 mL/min/1.73m^2) |
| Group 6 | Experimental | Drug: AMG 423Normal renal function (eGFR >or = 80mL/min/1.73m^2) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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;
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 423omecamtiv mecarbil | Drug | Group 1, Group 2, Group 3, Group 4, Group 5, Group 6 |
Primary outcome
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).
4 secondary outcomes
Other Total AMG 423 PK Parameters
Time frame: Twenty time points, up to eight days
AMG 423 Dialysis Clearance
Time frame: Hours 4, 5, 6, 7 & 8 post-dose
AMG 423 Metabolites
Time frame: Twenty time points, up to eight days
Safety
Time frame: Up to 46 days, including a 28 day screening period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 423 in people with Heart Failure, run by Cytokinetics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AMG 423 Pharmacokinetic Parameters (time frame: Twenty time points, up to eight days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.