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Design of FLAIR: a Phase 2b Study of the 5-Lipoxygenase Activating Protein Inhibitor AZD5718 in Patients With Proteinuric CKD.
Heerspink, Hiddo J L; Law, Gordon; Psachoulia, Konstantina; Connolly, Kathleen; Whatling, Carl; Ericsson, Hans; Knöchel, Jane; Lindstedt, Eva-Lotte; MacPhee, Iain.
Afiliação
  • Heerspink HJL; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Law G; Early Biometrics & Statistical Innovation, Data Science and Artificial Intelligence, R&D, AstraZeneca, Gaithersburg, Maryland, USA.
  • Psachoulia K; Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
  • Connolly K; Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
  • Whatling C; Translational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Ericsson H; Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Knöchel J; Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Lindstedt EL; Research and Early Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • MacPhee I; Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Kidney Int Rep ; 6(11): 2803-2810, 2021 Nov.
Article em En | MEDLINE | ID: mdl-34805632
ABSTRACT

INTRODUCTION:

Patients with chronic kidney disease (CKD) remain at risk for kidney and cardiovascular events resulting from residual albuminuria, despite available treatments. Leukotrienes are proinflammatory and vasoconstrictive lipid mediators implicated in the etiology of chronic inflammatory diseases. AZD5718 is a potent, selective, and reversible 5-lipoxygenase activating protein (FLAP) inhibitor that suppresses leukotriene production.

METHODS:

FLAIR (FLAP Inhibition in Renal disease) is an ongoing phase 2b, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of AZD5718 in patients with proteinuric CKD with or without type 2 diabetes. Participants receive AZD5718 at 3 different doses or placebo once daily for 12 weeks, followed by an 8-week extension in which they also receive dapagliflozin (10 mg/d) as anticipated future standard of care. The planned sample size is 632 participants, providing 91% power to detect 30% reduction in urinary albumin-to-creatinine ratio (UACR) between the maximum dose of AZD5718 and placebo. The dose-response effect of AZD5718 on UACR after the dapagliflozin extension is the primary efficacy objective. Key secondary objectives are the dose-response effect of AZD5718 plus current standard of care on UACR and acute effects of treatment on the estimated glomerular filtration rate. Safety, tolerability, AZD5718 pharmacokinetics, and analyses of biomarkers that may predict or reflect response to AZD5718 are additional objectives.

CONCLUSION:

FLAIR will provide data on the effects of 5-lipoxygenase pathway inhibition in patients with proteinuric CKD with or without type 2 diabetes, and will form the basis for future clinical trials (ClinicalTrials.gov NCT04492722).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article