Heart FailurePhase 1NCT03276728
Study to Evaluate the Safety and Tolerability of AMG 986 in Healthy Volunteers and Heart Failure Patients
A Phase 1 study testing AMG 986 IV and AMG 986 PO in people with Heart Failure and Healthy Volunteer, run by Amgen at 25 sites in 9 countries.
Trial summary
To evaluate the safety and tolerability of ascending single (Part A) and ascending multiple (Part B) doses of AMG 986 in healthy adults and of ascending multiple oral doses of AMG 986 in heart failure patients (Part C). Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure, Healthy Volunteer
- What is being tested?
- AMG 986 IV and AMG 986 PO
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 182 participants
- Where
- 25 sitesin 9 countries
- Study dates
- 12 Aug 2016to 18 Apr 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
- Male and female subjects ≥ 18 to ≤ 55 years old with no history or evidence of clinically relevant medical disorders as determined by the investigator and the Amgen physician (Parts A and B only)
- Body mass index (BMI) between 18 and 35 kg/m^2, inclusive, at screening.
- Physical examination including vital signs, clinical laboratory values, and electrocardiograms (ECGs) are clinically acceptable to the investigator. Abnormal findings for healthy volunteers and unexpected findings for heart failure patient subjects will be discussed with Amgen prior to study enrollment.
- Women must be of non-reproductive potential (ie, postmenopausal)
- Men must agree to practice an acceptable method of effective birth control while on study through 11 weeks after receiving the last dose of investigational product (AMG 986 or placebo). Acceptable methods of effective birth control include sexual abstinence; vasectomy and testing that shows there are no sperm in the semen; or a condom with spermicide (men) in combination with barrier methods (diaphragm, cervical cap or cervical sponge), hormonal birth control or IUS (women).
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- Men must be willing to abstain from sperm donation while on study through 11 weeks after receiving the last dose of investigational product (AMG 986 or placebo).
- This inclusion criterion only applies to Parts B and C cohorts. Before inclusion in the study, subjects will undergo a screening echocardiogram to ensure that the following parameters can be accurately measured: left ventricular end-systolic and end-diastolic volumes, left atrial end-systolic and end-diastolic volumes, ejection fraction, fraction shortening, and end-systolic septal and posterior wall thickness.
- For Part C
- Additional Inclusion Criteria for HFrEF Patients:
- Subject must be of age 18 to 85 years, have a diagnosis of HF confirmed by medical records for ≥ 3 months, and be in stable condition for at least 4 weeks.
- Left ventricular ejection fraction (LVEF) ≤ 40% confirmed by echocardiogram, radionuclide ventriculography, cardiac magnetic resonance imaging, or contrast ventriculography within 12 months prior to randomization.
- New York Heart Association (NYHA) class II or III at screening
- Sinus rhythm
- N-terminal pro b-type natriuretic peptide (NT-proBNP) level ≥ 250 pg/ml
- Patients will be treated with stable, optimal pharmacological therapy for a minimum of 4 weeks prior to randomization. Treatment of HFrEF includes at least beta-blockers (carvedilol, metoprolol succinate or bisoprolol) and a RAAS inhibitor (ACEi, ARB or sacubitril/valsartan).
- Additional Inclusion Criteria for HFpEF patients:
- Subject must be of age of 18 to 85 years, have a diagnosis of HF confirmed by medical records for ≥ 3 months, and be in stable condition for at least 4 weeks.
- LVEF ≥ 50% confirmed by echocardiogram, radionuclide ventriculography, cardiac magnetic resonance imaging, or contrast ventriculography within 12 months prior to randomization.
- LVEF never ≤ 40% in the past
- NYHA class II or III at screening
- Sinus rhythm
- NT-proBNP level ≥ 250 pg/ml
- Patients will be treated with stable, optimal pharmacological therapy for a minimum of 4 weeks prior to randomization. Treatment of HFpEF includes at least a daily dose of diuretics equivalent to furosemide 40 mg.
- For subjects in Parts A, B and C: Women must have negative results for both the screening (serum) and day -1 (serum or urine) pregnancy tests
Who cannot join
- Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives (whichever is longer), since ending treatment on another investigational device or drug study(s) prior to receiving the first dose of investigational product (AMG 986 or placebo).
- Female subjects who are lactating/breastfeeding or who plan to breastfeed while on study through 11 weeks after receiving the last dose of investigational product (AMG 986 or placebo).
- Male subjects with partners who are pregnant or planning to become pregnant while the subject is on study through 11 weeks after receiving the last dose of investigational product (AMG 986 or placebo).
- Female subjects of reproductive potential.
- Subjects in Parts A and B of the study: estimated glomerular filtration rate (eGFR) within the screening period of less than 60 mL/min/1.73m^2 as calculated using the estimated Modification of Diet in Renal Disease (MDRD) formula.
- Current or prior malignancy within 5 years of randomization, with the exception of non-melanoma skin cancers, cervical or breast ductal carcinoma in situ, and adenocarcinoma of the prostate Stage I or IIa (defined as T1, T2a or T2b, N0, M0 with documented serum prostate-specific antigen (PSA) < 20 ng/mL and Gleason score ≤ 7) per the American Joint Committee on Cancer (AJCC) primary tumor, regional lymph nodes, and distant metastasis system.
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- Positive results for human immunodeficiency virus (HIV), antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HepCAb).
- Subject has known sensitivity to any of the products or components to be administered during dosing.
- Subject likely to not be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
- History or evidence of any other clinically significant disorder, condition or disease with the exception of those outlined above that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- Subject previously has entered this study or has been previously exposed to AMG 986.
- Concurrent or prior use of strong CYP3A4 inhibitors within 14 days of study Day 1, including (not limited to): macrolide antibiotics (eg, clarithromycin, telithromycin), antifungals (eg, itraconazole, voriconazole), antivirals (eg, ritonavir, saquinavir, indinavir, nelfinavir), nefazodone.
- Concurrent or prior ingestion of grapefruit or grapefruit products and other foods that are known to inhibit CYP3A4 within 7 days of study Day 1.
- Concurrent or prior use of strong CYP3A4 inducers within 28 days of study Day 1, Including (not limited to): phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital. Subjects should also not take St John's Wort.
- Concurrent or prior use of strong P-glycoprotein inhibitors within 28 days of study Day 1, including (not limited to): elacridar and valspodar.
- All herbal supplements, vitamins, and nutritional supplements taken within the last 30 days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed and approved by the PI and Amgen Medical Monitor.
- For subjects enrolled under Amendments 1-6, inclusive: QTc > 450 msec or history/evidence of long QT syndrome.
- Planned elective surgery within 30 days of study completion or before return of red blood cell parameters to normal values.
- Blood donation ≥ 500 mL within 60 days of Day 1.
- Systolic blood pressure > 150 mmHg or < 90 mmHg, or diastolic blood pressure > 95 mmHg or < 60 mmHg, assessed on 2 separate occasions prior to enrollment (Parts A and B only).
- Heart rate ≥ 100 beats per minute after 5 minutes of rest or an untreated symptomatic bradyarrhythmia within 1 month prior to enrollment.
- For Parts A and B: Troponin I at screening > upper limit of normal (ULN).
- In the opinion of the Investigator, a condition that compromises the ability of the subject to give written informed consent or to comply with study procedures.
- Unwilling or unable to abstain from nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, pipes, or nicotine patches) throughout the screening period and for the duration of the study.
- Subjects who are unwilling or unable to limit alcohol consumption to 1 units/day (1 unit = 1 drink and 1 drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine or 1.5 ounces of 80 proof distilled spirits).
- Subjects with a positive urine drug screen or alcohol breath test.
- Known history of drug or alcohol abuse.
- Concurrent use of phosphodiesterase 5 (PDE5) inhibitors including (not limited to) avanafil, sildenafil, tadalafil, vardenafil.
- Concurrent use of vasodilators by healthy subjects in Parts A and B that could in the opinion of the investigator potentially lead to a drop in blood pressure in combination with investigational product.
- Severe uncorrected valvular heart disease, or hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease.
- For subjects in Part C of the study: eGFR within the screening period of less than 30 mL/min/1.732m^2 as calculated using the MDRD formula.
- For subjects in Part C of the study: Systolic blood pressure > 160 mmHg or < 100 mmHg, or diastolic blood pressure > 110 mmHg or < 60 mmHg, assessed on 2 separate occasions prior to enrollment.
- For subjects in Part C of the study: troponin I > ULN if there is also evidence of an acute cardiovascular event.
- For subjects enrolled in Part C under Amendment 7: QTc > 500 msec or history/evidence of long QT syndrome.
Trial locations and contacts
25 sites in 9 countries.
25 sites in 9 countries
United States8 sites
Research Site
Anaheim, California, 92801
Research Site
Baltimore, Maryland, 21201
Research Site
Durham, North Carolina, 27705
Research Site
Jacksonville, Florida, 32216
Research Site
Las Vegas, Nevada, 89148
Research Site
Metairie, Louisiana, 70006
Research Site
Minneapolis, Minnesota, 55415
Research Site
Tustin, California, 92780
Australia5 sites
Research Site
Auchenflower, Queensland, 4066
Research Site
Berwick, Victoria, 3806
Research Site
Bundaberg, Queensland, 4670
Research Site
Bundoora, Victoria, 3083
Research Site
Leabrook, South Australia, 5068
France4 sites
Research Site
Nantes, 44093
Research Site
Paris, 75015
Research Site
Rennes, 35033
Research Site
Toulouse, 31059
About this study
Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 986 in Healthy Subjects and Heart Failure Patients
To evaluate the safety and tolerability of ascending single (Part A) and ascending multiple (Part B) doses of AMG 986 in healthy adults and of ascending multiple oral doses of AMG 986 in heart failure patients (Part C).
Read the detailed description
This study is a randomized, placebo-controlled, double-blind, single day ascending dose (SDAD) study (Part A), a multiple daily ascending dose (MDAD) study (Part B), in healthy adults, and a MDAD study (Part C) in heart failure patients. In Parts A and B of the study, healthy volunteers will receive AMG 986 by continuous IV infusion or by oral administration in a fasted state. IV Infusions will be divided into an initial loading dose (LD) for the first hour followed immediately by a maintenance dose (MD).
In Part C of the study, patients with heart failure and either reduced (HFrEF) or preserved (HFpEF) ejection fraction will receive MDAD of AMG 986 or matching placebo once daily by oral administration for 21 days.
- Conditions
- Heart Failure, Healthy Volunteer
- Being tested
- AMG 986 IV, AMG 986 PO, Placebo PO, Placebo IV
- Keywords
- Heart Failure, Cardiovascular Diseases, Heart Diseases, Ejection fraction, Heart Failure with reduced ejection fraction, Heart Failure with preserved ejection fraction
- Medical subject headings
- Heart Failure, Cardiovascular Diseases, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 986 IVDrug
AMG 986 solution for infusion
AMG 986 PODrug
AMG 986 tablets for oral (PO) administration
Placebo PODrug
Matching placebo tablets for oral administration
Placebo IVDrug
Matching placebo solution for infusion
| Study group | Role | What they receive |
|---|---|---|
| Part A: Placebo | Placebo comparator | Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986. Receives: Drug: Placebo PO; Drug: Placebo IV |
| Part A: AMG 986 | Experimental | Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to to the Cohort 5 IV dosage consisting of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg. Receives: Drug: AMG 986 IV; Drug: AMG 986 PO |
| Part B: Placebo | Placebo comparator | Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986. Receives: Drug: Placebo PO; Drug: Placebo IV |
| Part B: AMG 986 | Experimental | Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on Day 1 and 38 mg lasting 24 hours on Days 2-4. IV cohort 2 was administered a loading dose of 60 mg over one hour followed by maintenance doses of 360 mg lasting 23 hours on Day 1 and 376 mg lasting 24 hours on Days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days. Receives: Drug: AMG 986 IV; Drug: AMG 986 PO |
| Part C: HFrEF Placebo | Placebo comparator | Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from Days 1-21. Receives: Drug: Placebo PO |
| Part C: HFpEF Placebo | Placebo comparator | Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from Days 1-21. Receives: Drug: Placebo PO |
| Part C: HFrEF AMG 986 | Experimental | Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21. Receives: Drug: AMG 986 PO |
| Part C: HFpEF AMG 986 | Experimental | Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21. Receives: Drug: AMG 986 PO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With Treatment Emergent Adverse Events (TEAE)
An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. Events categorized as TEAEs started on or after first dose of study drug and include up to 30 days after the last dose.
A serious AE is an AE that met one or more of the following criteria:
- Death
- Life-threatening
- Required inpatient hospitalization or prolongation of an existing hospitalization
- Resulted in persistent or significant disability/incapacity
- A congenital anomaly/birth defect
- Important medical events that required medical or surgical intervention to prevent one of the outcomes above.
Measured: Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51
Secondary outcomes (3)
Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
Heart failure (HF) refers to a clinical condition in which the cardiac output is insufficient to meet the metabolic needs of body organs and is marked by cardiac systolic and/or diastolic dysfunction. Heart failure with predominantly systolic dysfunction, which is identifiable as decreased contraction, is more aptly described as heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction and is measured by echocardiogram.
Measured: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction reported by volumetric method of disks (MoD) assessment.
Measured: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
Stroke Volume (Left Ventricular Outflow Tract Using Doppler Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction as measured using left ventricular outflow tract (LVOT) Doppler assessment.
Measured: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study start12 Aug 2016
- Primary completion18 Apr 2019
- Study completion18 Apr 2019
Why it stopped: Terminated (Decision by the Sponsor. The study was not terminated due to a safety reason.)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, placebo-controlled
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 182 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03276728
- Sponsor's protocol ID
- 20150183
- Other IDs
- 2017-002940-34, 2017
- Status last verified
- Mar 2022
- First submitted
- 17 Aug 2017
- Last updated
- 8 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
Winkle P, Goldsmith S, Koren MJ, Lepage S, Hellawell J, Trivedi A, Tsirtsonis K, Abbasi SA, Kaufman A, Troughton R, Voors A, Hulot JS, Donal E, Kazemi N, Neutel J. A First-in-Human Study of AMG 986, a Novel Apelin Receptor Agonist, in Healthy Subjects and Heart Failure Patients. Cardiovasc Drugs Ther. 2023 Aug;37(4):743-755. doi: 10.1007/s10557-022-07328-w. Epub 2022 Apr 23.
PubMed 35460392
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 986 in Healthy Subjects and Heart Failure Patients
- ClinicalTrials.gov ID
- NCT03276728
- Acronym / sponsor ID
- 20150183
- Conditions
- Heart Failure, Healthy Volunteer
- Keywords
- Heart Failure, Cardiovascular Diseases, Heart Diseases, Ejection fraction, Heart Failure with reduced ejection fraction, Heart Failure with preserved ejection fraction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated (Decision by the Sponsor. The study was not terminated due to a safety reason.)
- Enrolment
- 182 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 12 Aug 2016 (actual)
- Primary completion
- 18 Apr 2019 (actual)
- Study completion
- 18 Apr 2019 (actual)
- First posted
- 8 Sep 2017 (actual)
- Results
- Posted 8 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and tolerability of ascending single (Part A) and ascending multiple (Part B) doses of AMG 986 in healthy adults and of ascending multiple oral doses of AMG 986 in heart failure patients (Part C).
Detailed description
This study is a randomized, placebo-controlled, double-blind, single day ascending dose (SDAD) study (Part A), a multiple daily ascending dose (MDAD) study (Part B), in healthy adults, and a MDAD study (Part C) in heart failure patients. In Parts A and B of the study, healthy volunteers will receive AMG 986 by continuous IV infusion or by oral administration in a fasted state. IV Infusions will be divided into an initial loading dose (LD) for the first hour followed immediately by a maintenance dose (MD).
In Part C of the study, patients with heart failure and either reduced (HFrEF) or preserved (HFpEF) ejection fraction will receive MDAD of AMG 986 or matching placebo once daily by oral administration for 21 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
- Model description
- Double-blind, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| Part A: Placebo | Placebo comparator | Drug: Placebo PO, Drug: Placebo IVHealthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986. |
| Part A: AMG 986 | Experimental | Drug: AMG 986 IV, Drug: AMG 986 POHealthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to to the Cohort 5 IV dosage consisting of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg. |
| Part B: Placebo | Placebo comparator | Drug: Placebo PO, Drug: Placebo IVHealthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986. |
| Part B: AMG 986 | Experimental | Drug: AMG 986 IV, Drug: AMG 986 POHealthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on Day 1 and 38 mg lasting 24 hours on Days 2-4. IV cohort 2 was administered a loading dose of 60 mg over one hour followed by maintenance doses of 360 mg lasting 23 hours on Day 1 and 376 mg lasting 24 hours on Days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days. |
| Part C: HFrEF Placebo | Placebo comparator | Drug: Placebo POParticipants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from Days 1-21. |
| Part C: HFpEF Placebo | Placebo comparator | Drug: Placebo POParticipants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from Days 1-21. |
| Part C: HFrEF AMG 986 | Experimental | Drug: AMG 986 POParticipants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21. |
| Part C: HFpEF AMG 986 | Experimental | Drug: AMG 986 POParticipants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from Days 1-21 in ascending doses of 10 mg for Days 1-7, 30 mg for Days 8-14 and 100 mg for days 15-21. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
- Male and female subjects ≥ 18 to ≤ 55 years old with no history or evidence of clinically relevant medical disorders as determined by the investigator and the Amgen physician (Parts A and B only)
- Body mass index (BMI) between 18 and 35 kg/m^2, inclusive, at screening.
- Physical examination including vital signs, clinical laboratory values, and electrocardiograms (ECGs) are clinically acceptable to the investigator. Abnormal findings for healthy volunteers and unexpected findings for heart failure patient subjects will be discussed with Amgen prior to study enrollment.
- Women must be of non-reproductive potential (ie, postmenopausal)
Key exclusion criteria (34 listed)
- Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives (whichever is longer), since ending treatment on another investigational device or drug study(s) prior to receiving the first dose of investigational product (AMG 986 or placebo).
- Female subjects who are lactating/breastfeeding or who plan to breastfeed while on study through 11 weeks after receiving the last dose of investigational product (AMG 986 or placebo).
- Male subjects with partners who are pregnant or planning to become pregnant while the subject is on study through 11 weeks after receiving the last dose of investigational product (AMG 986 or placebo).
- Female subjects of reproductive potential.
- Subjects in Parts A and B of the study: estimated glomerular filtration rate (eGFR) within the screening period of less than 60 mL/min/1.73m^2 as calculated using the estimated Modification of Diet in Renal Disease (MDRD) formula.
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 986 IVAMG 986 solution for infusion | Drug | Part A: AMG 986, Part B: AMG 986 |
| AMG 986 POAMG 986 tablets for oral (PO) administration | Drug | Part A: AMG 986, Part B: AMG 986, Part C: HFpEF AMG 986, Part C: HFrEF AMG 986 |
| Placebo POMatching placebo tablets for oral administration | Drug | Part A: Placebo, Part B: Placebo, Part C: HFpEF Placebo, Part C: HFrEF Placebo |
| Placebo IVMatching placebo solution for infusion | Drug | Part A: Placebo, Part B: Placebo |
Primary outcome
Participants With Treatment Emergent Adverse Events (TEAE)
Time frame: Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51
An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. Events categorized as TEAEs started on or after first dose of study drug and include up to 30 days after the last dose. A serious AE is an AE that met one or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect * Important medical events that required medical or surgical intervention to prevent one of the outcomes above.
3 secondary outcomes
Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
Time frame: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
Time frame: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
Stroke Volume (Left Ventricular Outflow Tract Using Doppler Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort
Time frame: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35460392Winkle P, Goldsmith S, Koren MJ, Lepage S, Hellawell J, Trivedi A, Tsirtsonis K, Abbasi SA, Kaufman A, Troughton R, Voors A, Hulot JS, Donal E, Kazemi N, Neutel J. A First-in-Human Study of AMG 986, a Novel Apelin Receptor Agonist, in Healthy Subjects and Heart Failure Patients. Cardiovasc Drugs Ther. 2023 Aug;37(4):743-755. doi: 10.1007/s10557-022-07328-w. Epub 2022 Apr 23.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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
25 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 986 IV and AMG 986 PO in people with Heart Failure and Healthy Volunteer, run by Amgen at 25 sites in 9 countries.
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 25 inclusion and 34 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: stopped early, as of the sponsor's last update on 8 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Australia, France, Germany, Poland and 4 more countries. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 8 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Participants With Treatment Emergent Adverse Events (TEAE) (time frame: Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03276728, which also lists 1 linked publication.
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 8 Aug 2022.