884-P: Decentralized N=1 Study—A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin

Abstract

Background: The SGLT2 inhibitor dapagliflozin reduces kidney function decline and urine albumin:creatinine ratio (UACR) on a population level. However, there is marked heterogeneity in the efficacy among individual patients. We conducted a decentralized (i.e. at home) N=1 trial to assess the effect of dapagliflozin in individual patients and the feasibility of remote data collection. Methods: Twenty patients with type 2 diabetes, UACR >20 mg/g and eGFR >30 mL/min/1.73m2 entered the randomized placebo-controlled double-blind N=1 trial. Patients were randomly assigned to two periods of 1-week treatment with dapagliflozin 10 mg/day and two periods of 1-week treatment with placebo in random order with 1-week wash-out periods in between. Patients collected and sent their own data with automatic uploading to an online platform and sent early morning urines 5 times/week to the laboratory for albumin and creatinine assessment. Primary outcome was UACR change from baseline (mixed effects model). The study had 80% power to detect a correlation in UACR change between first and second dapagliflozin period of 0.6. Results: Patients had a mean eGFR of 70.2 mL/min/1.73m2 and median UACR of 94.7 mg/g. During the study, dapagliflozin compared to placebo reduced albuminuria by 15.1% (95%CI 3.3 - 28.2; p=0.013). There was a marked variation in the change from baseline in UACR during dapagliflozin treatment periods (range first and second exposure -26.9 to -4.7% and -30.5 to -5.8%, respectively). The individual change in UACR during the first and second exposure correlated in the dapagliflozin periods (r=0.50; p=0.026) but not in the placebo periods (r=0.09; p=0.69). Of all scheduled urine collections (N=816), only 5 collections (0.61%) were not delivered in the laboratory. Conclusion: The individual UACR response to dapagliflozin varies among individual patients and is consistent upon re-exposure. Remote data collection was very reliable with nearly any missed urine collection. Disclosure J.Beernink: None. G.D.Laverman: Advisory Panel; AstraZeneca, Vifor Pharma Management Ltd., Boehringer Ingelheim Inc., Astellas Pharma Inc., Lilly, Other Relationship; Sanofi, AstraZeneca. H.L.Heerspink: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Bayer Inc., Eli Lilly and Company, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., George Clinical, Merck & Co., Inc., Janssen Research & Development, LLC, Traveere Pharmaceuticals, Novo Nordisk. N.Jongs: Speaker's Bureau; AstraZeneca.