Evidence map›Paper›PMID 35460392›Full record

Trial reportCardiovascular drugs and therapy2023

A First-in-Human Study of AMG 986, a Novel Apelin Receptor Agonist, in Healthy Subjects and Heart Failure Patients.

Peter Winkle, Steven Goldsmith, Michael J Koren, Serge Lepage, Jennifer Hellawell, Ashit Trivedi, Kate Tsirtsonis, Siddique A Abbasi, Allegra Kaufman, Richard Troughton and 5 more

Registry-linked trialOpen access · greenAbstract readRandomized Controlled TrialClinical Trial, Phase I
PubMed Publisher
In one paragraph

Trial report in Cardiovascular drugs and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03276728 (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), which is not on this map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03276728 phase1terminatednot on this map

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

TypeinterventionalSponsorAmgenRan2016 to 2019Enrolled182ConditionsHeart Failure, Healthy VolunteerArmsAMG 986 IV, AMG 986 PO, Placebo PO, Placebo IV
3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 30 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 11 institutions in 6 countries.

Peter WinkleAnaheim Clinical Trials, 2441 W La Palma Ave, Anaheim, CA, 92801, USA.
Steven GoldsmithHennepin Healthcare and the University of Minnesota, 715 S 8 St, Minneapolis, MN, 55415, USA.
Michael J KorenJacksonville Center for Clinical Research, 4085 University Blvd S #1, Jacksonville, FL, 32216, USA.
Serge LepageDepartment of Medicine, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, Québec, J1H 5N4, Canada.
Jennifer HellawellAmgen Inc., 1120 Veterans Blvd, South San Francisco, CA, 94080, USA. jhellawe@amgen.com.
Ashit TrivediAmgen Inc., One Amgen Center Dr, Thousand Oaks, CA, 91320, USA.
Kate TsirtsonisAmgen Limited, 1 Uxbridge Business Park, Sanderson Rd, Uxbridge, UB8 1DH, UK.
Siddique A AbbasiAmgen Inc., One Amgen Center Dr, Thousand Oaks, CA, 91320, USA.
Allegra KaufmanAmgen Inc., One Amgen Center Dr, Thousand Oaks, CA, 91320, USA.
Richard TroughtonDepartment of Medicine, Christchurch Heart Institute, University of Otago, PO Box 4345, Christchurch, 8140, New Zealand.
Adriaan VoorsDepartment of Cardiology (AB31), University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jean-Sebastien HulotUniversité de Paris, INSERM, PARCC, F-75006, Paris, France.
Erwan DonalUniversitaire Rennes, Centre Hospitalier Universitaire de Rennes, INSERM, LTSI - UMR 1099, 2 rue Henri Le Guilloux 35033, 35000, Rennes, France.
Navid KazemiPalm Research Center, Inc., 9280 W Sunset Rd, Suite 306, Las Vegas, NV, 89148, USA.
Joel NeutelOrange County Research Center, 14351 Myford Rd, Suite B, Tustin, CA, 92780, USA.
Amgen (United States) · USAnaheim Clinical Trials · USBrunel University of London · GBCentre Hospitalier Universitaire de Rennes · FRHennepin Healthcare Research Institute · USHôpital Européen Georges-Pompidou · FRJacksonville Center for Clinical Research · USOrange County Research Center · USUniversité de Sherbrooke · CAUniversity Medical Center Groningen · NLUniversity of Otago · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeAMG 986 is a novel apelin receptor (APJ) agonist that improves cardiac contractility in animal models without adversely impacting hemodynamics. This phase 1b study evaluated the safety/tolerability, pharmacokinetics, and pharmacodynamics of AMG 986 in healthy subjects and patients with heart failure (HF).

methodsHealthy adults (Parts A/B) and HF patients (Part C) aged 18-85 years were randomized 3:1 to single-dose oral/IV AMG 986 or placebo (Part A); multiple-dose oral/IV AMG 986 or placebo (Part B); or escalating-dose oral AMG 986 or placebo (Part C). PRIMARY ENDPOINT: treatment-emergent adverse events, laboratory values/vital signs/ECGs; others included AMG 986 pharmacokinetics, left ventricular (LV) function.

resultsOverall, 182 subjects were randomized (AMG 986/healthy: n = 116, placebo, n = 38; AMG 986/HF: n = 20, placebo, n = 8). AMG 986 had acceptable safety profile; no clinically significant dose-related impact on safety parameters up to 650 mg/day was observed. AMG 986 exposures increased nonlinearly with increasing doses; minimal accumulation was observed. In HF with reduced ejection fraction patients, there were numerical increases in percent changes from baseline in LV ejection fraction and stroke volume by volumetric assessment with AMG 986 vs placebo (stroke volume increase not recapitulated by Doppler).

conclusionsIn healthy subjects and HF patients, short-term AMG 986 treatment was well tolerated. Consistent with this observation, clinically meaningful pharmacodynamic effects in HF patients were not observed. Changes in ejection fraction and stroke volume in HF patients suggest additional studies may be needed to better define the clinical utility and optimal dosing for this molecule. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03276728. DATE OF REGISTRATION: September 8, 2017.

Indexed as

Heart FailureAdultApelin ReceptorsDouble-Blind MethodHealthy VolunteersHumansStroke VolumeVentricular Function, LeftApelin ReceptorsAMG 986Apelin receptor agonistHeart failure

Identifiers

PMID35460392
OpenAlexW4224270466

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.