Journal
KIDNEY INTERNATIONAL REPORTS
Volume 6, Issue 11, Pages 2803-2810Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ekir.2021.08.018
Keywords
albuminuria; chronic kidney disease; diabetic kidney disease; leukotriene; 5-lipoxygenase activating protein; randomized controlled clinical trial
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Funding
- AstraZeneca
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The FLAIR study is evaluating the efficacy and safety of AZD5718 in patients with proteinuric CKD, with the primary objective being the dose-response effect of AZD5718 on UACR after the dapagliflozin extension. Key secondary objectives include the dose-response effect of AZD5718 plus current standard of care on UACR and acute effects of treatment on the estimated glomerular filtration rate.
Introduction: Patients with chronic kidney disease (CKD) remain at risk for kidney and cardiovascular events resulting from residual albuminuria, despite available treatments. Leukotrienes are proin-flammatory and vasoconstrictive lipid mediators implicated in the etiology of chronic inflammatory dis-eases. AZD5718 isa 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 ana-lyses 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.
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