Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Participants With Severely Impaired Renal Function

A Phase 1 study testing AMG 986 in people with Heart Failure, run by Amgen at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

A study to assess the safety, tolerability, and pharmacokinetics of AMG 986 given orally as a single dose to healthy participants and participants with severely impaired kidney function. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Heart Failure
What is being tested?: AMG 986
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 4 sitesUnited States
Study dates: 12 Dec 2017to 5 Apr 2018
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 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Male or female subjects, who are > or = 18 and < or = 65 years of age at the time of screening
Subject has provided informed consent prior to initiation of any study-specific activities/procedures
Women must be of non-reproductive potential (ie, postmenopausal, history of hysterectomy, or history of bilateral oophorectomy)
Men must agree to practice an acceptable method of effective birth control while on study through 11 weeks after receiving the dose of study drug.
Men must be willing to abstain from sperm donation while on study through 11 weeks after receiving the dose of study drug
Body Mass Index > or = 18 and < or = 38 kg/m^2 at screening

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Physical examination and 12-lead electrocardiograms (ECGs) are clinically acceptable to the investigator
Non-hypertensive subjects or subjects with treated, stable hypertension as defined by blood pressure not exceeding 170/100 mm Hg as an average during screening and day -1; for subjects with renal impairment, no change in dosage and medication for > or = 4 weeks prior to screening, and expected to remain on this dose and medication for the entire duration of the study
Willing to maintain current general diet and physical activity regimen
Renal function in 1 of the following 2 categories at the time of screening: Group 1 - Severe Renal Impairment (eGFR 15 to 29 mg/min/1.73 m^2) and not anticipated to require hemodialysis or renal transplantation, and anticipated to have renal function appropriate to severe renal impairment for the duration of the study OR Group 2 - Normal renal function (eGFR > or = 90 mg/min/1.73 m^2)

Who cannot join

Subjects whose second modification of diet in renal disease (MDRD) eGFR result on day -1 is not within 15% of the first eGFR result performed during the screening period. Healthy volunteers who have normal renal function, but show a difference greater than 15% in eGFR based on MDRD during the screening period, will be included in the trial at the discretion of the investigator and the sponsor after a 24-hour creatinine clearance has been performed that meets eligibility criteria.
Subjects who are the recipient of a renal transplant and/or are on immunosupressants.
Subjects with a history of hospitalization for heart disease or angina within 4 months of screening.
Current or prior malignancy within 5 years of enrollment 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.
Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HepCAb) at screening
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.

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Subject previously has entered this study or has been previously exposed to AMG 986.
Heart rate ≥ 100 beats per minute after 5 minutes of rest or an untreated symptomatic bradyarrhythmia within 1 month prior to enrollment.
Known history of drug or alcohol abuse within last 12 months.
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 dose of investigational product (AMG 986).

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Research Site
Minneapolis, Minnesota, 55404
Research Site
Orlando, Florida, 32809
Research Site
San Antonio, Texas, 78215
Research Site
Tustin, California, 92780

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Single-dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Subjects With Severely Impaired Renal Function

A study to assess the safety, tolerability, and pharmacokinetics of AMG 986 given orally as a single dose to healthy participants and participants with severely impaired kidney function.

Conditions: Heart Failure
Being tested: AMG 986
Keywords: Cardiovascular Diseases, Renal Impairment, Heart Diseases
Medical subject headings: Heart Failure, Cardiovascular Diseases, Renal Insufficiency, Heart Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AMG 986Drug
tablets for oral administration

Study groups in NCT03318809
Study group	Role	What they receive
Group 1: Severely Renal Impaired Participants	Experimental	Participants with severely impaired renal function (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m^2) receive a single oral dose of 200 mg AMG 986. Receives: Drug: AMG 986
Group 2: Healthy Participants	Active comparator	Participants with normal renal function (eGFR >= 90 mL/min/1.73 m^2 or above) receive a single oral dose of 200 mg AMG 986. Receives: Drug: AMG 986

What is being measured

The primary outcome is the main question the study is designed to answer.

AMG 986 Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast)
Measured: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Maximum Observed Plasma Concentration After Dosing (Cmax)
Measured: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Terminal Phase Half-Life (t1/2,z)
Measured: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Time of Maximum Plasma Concentration (Tmax)
Measured: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUCinf)
Measured: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Secondary outcomes (1)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event is defined as any untoward medical occurrence in a clinical trial subject. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:
- fatal
- life threatening (places the subject at immediate risk of death)
- requires in patient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability/incapacity
- congenital anomaly/birth defect
- other medically important serious event
Measured: From first dose of study drug up to Day 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Dec 20175 Apr 2018

First posted24 Oct 2017
Study start12 Dec 2017
Primary completion12 Mar 2018
Study completion5 Apr 2018

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: Non-randomised
Intervention model: Parallel groups
Model description: This is a multisite (approximately 3 sites), open-label, non-randomized, single-dose study in participants with severely impaired kidney function and healthy participants. About 12 participants will be assigned to two groups: Group 1: 6 with severely impaired kidney function , and Group 2: 6 with normal kidney function.
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03318809
Sponsor's protocol ID: 20150186
Status last verified: Jun 2022
First submitted: 6 Oct 2017
Last updated: 23 Jun 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

Trivedi A, Mather O, Vega S, Simiens MA, Hellawell J, Lee E. Effect of Severe Renal Impairment on the Safety, Tolerability, and Pharmacokinetics of AMG 986. Drugs R D. 2022 Mar;22(1):89-94. doi: 10.1007/s40268-021-00380-1. Epub 2022 Jan 29.
PubMed 35092583

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic

All Heart Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Single-dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Subjects With Severely Impaired Renal Function
ClinicalTrials.gov ID: NCT03318809
Acronym / sponsor ID: 20150186
Conditions: Heart Failure
Keywords: Cardiovascular Diseases, Renal Impairment, Heart Diseases
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 12 Dec 2017 (actual)
Primary completion: 12 Mar 2018 (actual)
Study completion: 5 Apr 2018 (actual)
First posted: 24 Oct 2017 (actual)
Results: Posted 27 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A study to assess the safety, tolerability, and pharmacokinetics of AMG 986 given orally as a single dose to healthy participants and participants with severely impaired kidney function.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: This is a multisite (approximately 3 sites), open-label, non-randomized, single-dose study in participants with severely impaired kidney function and healthy participants. About 12 participants will be assigned to two groups: Group 1: 6 with severely impaired kidney function , and Group 2: 6 with normal kidney function.

Arm	Type	Receives
Group 1: Severely Renal Impaired Participants	Experimental	Drug: AMG 986Participants with severely impaired renal function (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m^2) receive a single oral dose of 200 mg AMG 986.
Group 2: Healthy Participants	Active comparator	Drug: AMG 986Participants with normal renal function (eGFR >= 90 mL/min/1.73 m^2 or above) receive a single oral dose of 200 mg AMG 986.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Male or female subjects, who are > or = 18 and < or = 65 years of age at the time of screening
Subject has provided informed consent prior to initiation of any study-specific activities/procedures
Women must be of non-reproductive potential (ie, postmenopausal, history of hysterectomy, or history of bilateral oophorectomy)
Men must agree to practice an acceptable method of effective birth control while on study through 11 weeks after receiving the dose of study drug.
Men must be willing to abstain from sperm donation while on study through 11 weeks after receiving the dose of study drug

Key exclusion criteria (10 listed)

Subjects whose second modification of diet in renal disease (MDRD) eGFR result on day -1 is not within 15% of the first eGFR result performed during the screening period. Healthy volunteers who have normal renal function, but show a difference greater than 15% in eGFR based on MDRD during the screening period, will be included in the trial at the discretion of the investigator and the sponsor after a 24-hour creatinine clearance has been performed that meets eligibility criteria.
Subjects who are the recipient of a renal transplant and/or are on immunosupressants.
Subjects with a history of hospitalization for heart disease or angina within 4 months of screening.
Current or prior malignancy within 5 years of enrollment 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.
Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HepCAb) at screening

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 986tablets for oral administration	Drug	Group 1: Severely Renal Impaired Participants, Group 2: Healthy Participants

Primary outcome

AMG 986 Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast)
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Maximum Observed Plasma Concentration After Dosing (Cmax)
Time frame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Terminal Phase Half-Life (t1/2,z)
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Time of Maximum Plasma Concentration (Tmax)
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUCinf)
Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

1 secondary outcome

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to Day 30

Results and safety

Results posted to the registry on 27 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1: Severely Renal Impaired Participants	6	6
Group 2: Healthy Participants	6	6

Primary outcome: AMG 986 Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast)

Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: hr*ng/mL

Measure	Group 1: Severely Renal Impaired Participants n = 6	Group 2: Healthy Participants n = 6
Value	80,000 (33.6)	64,500 (70.0)

Group 1: Severely Renal Impaired Participants vs Group 2: Healthy Participants: Ratio (Group 1/Group 2): 1.24 (90% CI 0.73 to 2.10)

Population analysed: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

Primary outcome: AMG 986 PK Parameter: Maximum Observed Plasma Concentration After Dosing (Cmax)

Time frame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Group 1: Severely Renal Impaired Participants n = 6	Group 2: Healthy Participants n = 6
Value	10,600 (45.3)	7520 (50.5)

Group 1: Severely Renal Impaired Participants vs Group 2: Healthy Participants: Ratio (Group 1/Group 2): 1.41 (90% CI 0.88 to 2.27)

Population analysed: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

Primary outcome: AMG 986 PK Parameter: Terminal Phase Half-Life (t1/2,z)

Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: hours

Measure	Group 1: Severely Renal Impaired Participants n = 6	Group 2: Healthy Participants n = 6
Value	18.4 (21.1)	21.1 (44.6)

Population analysed: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

Primary outcome: AMG 986 PK Parameter: Time of Maximum Plasma Concentration (Tmax)

Time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose. Median (Full Range). Unit: hours

Measure	Group 1: Severely Renal Impaired Participants n = 6	Group 2: Healthy Participants n = 6
Value	1.1 (1.0 to 2.1)	1.5 (1.1 to 4.1)

Population analysed: The PK analysis set included all participants for whom at least 1 PK parameter or endpoint could be reliably estimated.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From first dose of study drug up to Day 30. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1: Severely Renal Impaired Participants	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Group 2: Healthy Participants	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 35092583Trivedi A, Mather O, Vega S, Simiens MA, Hellawell J, Lee E. Effect of Severe Renal Impairment on the Safety, Tolerability, and Pharmacokinetics of AMG 986. Drugs R D. 2022 Mar;22(1):89-94. doi: 10.1007/s40268-021-00380-1. Epub 2022 Jan 29.
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

Related trials for Heart Failure

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
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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

4 sites 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 986 in people with Heart Failure, run by Amgen at 4 sites 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 10 inclusion and 10 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 23 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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?

Yes. Results are posted in the registry (first posted 27 Jan 2021). 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?

AMG 986 Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast) (time frame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose). The study lists 5 primary outcomes in all. 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 NCT03318809, 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 23 Jun 2022.