Efficacy of a novel inhibitor of vascular adhesion protein-1 in reducing albuminuria in patients with diabetic kidney disease (ALBUM): a randomised, placebo-controlled, phase 2 trial.
| Autor: | de Zeeuw D; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. Electronic address: d.de.zeeuw@umcg.nl., Renfurm RW; Astellas Pharma Global Development, Astellas Pharma Europe BV, Leiden, Netherlands., Bakris G; American Society of Hypertension Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, IL, USA., Rossing P; Steno Diabetes Center and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Perkovic V; The George Institute for Global Health, University of New South Wales Sydney, Newtown, NSW, Australia., Hou FF; Department of Internal Medicine, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney Disease, Guangzhou, China., Nangaku M; University of Tokyo School of Medicine, Tokyo, Japan., Sharma K; Department of Medicine, University of Texas Health Science Center at San Antonio, Bio-X Institutes, San Antonio, TX, USA., Heerspink HJL; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands., Garcia-Hernandez A; Astellas Pharma Global Development, Astellas Pharma Europe BV, Leiden, Netherlands., Larsson TE; Astellas Pharma Global Development, Astellas Pharma Europe BV, Leiden, Netherlands. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | The lancet. Diabetes & endocrinology [Lancet Diabetes Endocrinol] 2018 Dec; Vol. 6 (12), pp. 925-933. Date of Electronic Publication: 2018 Nov 06. |
| DOI: | 10.1016/S2213-8587(18)30289-4 |
| Abstrakt: | Background: Many patients with diabetic kidney disease have residual albuminuria and are at risk of disease progression. The ALBUM trial investigated the efficacy of a novel, orally active inhibitor of vascular adhesion protein-1, ASP8232, compared with placebo for reducing albuminuria in individuals with type 2 diabetes and chronic kidney disease. Methods: In this randomised, double-blind, placebo-controlled phase 2 trial, we randomly assigned individuals (aged 18-85 years) from 64 clinical sites in nine European countries to receive ASP8232 40 mg or placebo orally once daily for 12 weeks using a web-based randomisation schedule (block size 4), stratified by country. Eligible patients had a urinary albumin-to-creatinine ratio (UACR) of 200-3000 mg/g, an estimated glomerular filtration rate of at least 25 mL/min per 1·73 m 2 but lower than 75 mL/min per 1·73 m 2 , HbA Findings: 125 participants were randomly assigned to receive ASP8232 (n=64) or placebo (n=61), of whom 120 (60 in each group) were included in the full analysis set; all participants were assessed for safety endpoints. At 12 weeks, UACR decreased by 17·7% (95% CI 5·0 to 28·6) in the ASP8232 group and increased by 2·3% (-11·4 to 18·1) in the placebo group; the placebo-adjusted difference between groups was -19·5% (95% CI -34·0 to -1·8; p=0·033). 39 (61%) patients in the ASP8232 group and 34 (56%) patients in the placebo group had a treatment-emergent adverse event, of which 16 in the ASP8232 group and four in the placebo group were drug-related. The most frequently reported adverse events that were possibly drug-related in the ASP8232 group were renal impairment (five patients) and decreased eGFR (three patients); in the placebo group, no single drug-related treatment-emergent adverse event was reported by more than one participant. Interpretation: ASP8232 is effective in reducing albuminuria in patients with diabetic kidney disease and is safe and well tolerated. These findings warrant further research to ascertain the effect of ASP8232 on delaying progression of diabetic kidney disease. Funding: Astellas. (Copyright © 2018 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|