15-LB: Safety and Efficacy of Tetramethylpyrazine Nitrone in Treating Patients with Type 2 Diabetes and Microalbuminuria—A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial

Abstract

Background and purpose: Tetramethylpyrazine nitrone (TBN) is a multi-functional agent that has shown kidney protective effects in preclinical studies. TBN has a unique mechanism of action, i.e., scavenging free radicals and activating AMPK/PGC-1α/NRF2 pathway. This phase II clinical trial investigated the safety and efficacy of TBN in patients with early diabetic kidney disease (DKD) . Methods: This multicenter, randomized, double-blind, placebo-controlled trial enrolled 143 Chinese type 2 diabetic patients (T2DM) with microalbuminuria (urinary albumin-to-creatinine ratio ≥ 30 to <300 mg/g creatinine) treated with or without renin-angiotensin system inhibitor who had eGFR ≥60 ml/min per 1.73 m2. Participants were randomized (1:1:1:1) to receive 300 mg, 600 mg or 1200 mg TBN bid or placebo for 180 days. The primary outcome was change in urinary albumin-to-creatinine ratio (UACR) from baseline to day 180. The safety outcome included any adverse events during 180 days. Results: TBN was safe and well-tolerated. There were no statistical differences among the incidences of drug-related adverse event among the TBN and the placebo groups. TBN (600 mg, bid) decreased UACR by -46.56% [90% CI,-61.15, -1.74, p>0.99] from baseline to day 180 versus -14.33% [90% CI, -38.26, 19.39] in the placebo group. The proportion of patients with ≥ 30% reduction in UACR was 54.8% [95% CI, -9.10, 38.26, p=0.216] in the TBN (600 mg) group versus 39.4% in the placebo group. The change in eGFR from baseline to day 180 was 0 [95% CI, -6.66, 5.00, p>0.99] in the TBN (600 mg) group versus a decline of -2.12% [95% CI, -11.90, -0.63] in the placebo group. Conclusions: TBN is a promising new treatment for early DKD and its safety and efficacy will be further investigated in clinical trials. Disclosure J. Yang: None. Funding Guangzhou Magpie Pharmaceutical Co. Ltd (CTR20220455)