Trial reportBritish journal of clinical pharmacology2017
Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949.
Trial report in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 70 citations in OpenAlex.
- Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949.British journal of clinical pharmacology · 2017Trial
- Unique fluoroalkyl substituents: is there life after CFChemical science · 2026Review
- Inflammation and Resolution in Obesity-Related Cardiovascular Disease.International journal of molecular sciences · 2026Review
- Investigation into ligand selectivity and bias at the formyl peptide receptor family.The Journal of pharmacology and experimental therapeutics · 2026Article
- Resolution Pharmacology: State-of-the-art and therapeutic landscape.Pharmacological reviews · 2025Review
- Design, Synthesis, and Biological Evaluation of Novel Heteroaryl, Squaramide, and Indolcarboxamide Derivatives as Formyl Peptide Receptor 2 Agonists to Target Neuroinflammation.ACS chemical neuroscience · 2025Article
- Inflammaging and Immunosenescence in the Post-COVID Era: Small Molecules, Big Challenges.ChemMedChem · 2025Review
- Review of methodology and re-analysis of lipidomic data focusing on specialised pro-resolution lipid mediators (SPMs) in a human model of resolving inflammation.International journal of experimental pathology · 2025Review
- Molecular dynamics of inflammation resolution: therapeutic implications.Frontiers in cell and developmental biology · 2025Review
- TheFrontiers in immunology · 2025Review
- First-in-human study to evaluate the safety, tolerability, and population pharmacokinetic/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects.Antimicrobial agents and chemotherapy · 2024Article
- Structural basis of G protein-Coupled receptor CMKLR1 activation and signaling induced by a chemerin-derived agonist.PLoS biology · 2023Article
- Endogenous inhibitory mechanisms in asthma.The journal of allergy and clinical immunology. Global · 2023Review
- Molecular Mechanisms of Desensitization Underlying the Differential Effects of Formyl Peptide Receptor 2 Agonists on Cardiac Structure-Function Post Myocardial Infarction.ACS pharmacology & translational science · 2022Article
- Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35.British journal of pharmacology · 2022Review
- Annexin-A1: The culprit or the solution?Immunology · 2022Review
- Molecular Pharmacology of Inflammation Resolution in Atherosclerosis.International journal of molecular sciences · 2022Review
- Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2.Nature communications · 2022Article
- Targeting Neutrophils for Promoting the Resolution of Inflammation.Frontiers in immunology · 2022Review
- Synthesis, biological evaluation, molecular modeling, and structural analysis of new pyrazole and pyrazolone derivatives as N-formyl peptide receptors agonists.Chemical biology & drug design · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe main objectives of these two phase I studies were to investigate safety and tolerability as well as the pharmacokinetic/pharmacodynamic profile of the novel potent and selective formyl peptide receptor type 2 (FPR2)/Lipoxin A
methodsTwo double-blind, randomized phase I studies investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of ACT-389949 at different doses and dosing regimens. Drug exposure was correlated with target engagement markers such as receptor internalization and cytokine measurements. The effect of FPR2/ALX agonism on neutrophil migration was studied in a lipopolysaccharide (LPS) inhalation model.
resultsACT-389949 was well tolerated. Maximum concentrations were reached around 2 h after dosing, with a mean terminal half-life of 29.3 h [95% confidence interval (CI) 25.5, 33.7]. After multiple-dose administration, exposure increased by 111% (95% CI 89, 136), indicating drug accumulation. Administration of ACT-389949 resulted in a dose-dependent, long-lasting internalization of FPR2/ALX into leukocytes. Pro- and anti-inflammatory cytokines were dose-dependently but transiently upregulated only after the first dose. No pharmacological effect on neutrophil count was observed in the LPS challenge test performed at steady state.
conclusionsFPR2/ALX agonism with ACT-389949 was shown to be safe and well tolerated in healthy subjects. Receptor internalization and downstream mediators pointed towards a desensitization of the system, which may explain the lack of effect on neutrophil recruitment in the LPS challenge model.
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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.