Randomized, double-blind, placebo-controlled phase 3 study of bardoxolone methyl in patients with diabetic kidney disease: design and baseline characteristics of the AYAME study

Background Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD), but currently available treatments do not improve kidney function or prevent the initiation of dialysis/kidney replacement therapy. A previous study demonstrated that bardoxolone methyl improves the estimated glomerular filtration rate (eGFR), but the study was prematurely terminated because of an imbalance in heart failure between treatment groups. The subsequent phase 2 TSUBAKI study demonstrated no incidence of heart failure and an improved eGFR and GFR as determined by inulin clearance in DKD patients. Methods This randomized, double-blind, placebo-controlled multicentre phase 3 study was designed to assess the efficacy and safety of bardoxolone methyl in DKD patients with an eGFR >= 15.0-<60.0 ml/min/1.73 m(2) and a urinary albumin:creatinine ratio (UACR) <= 3500 mg/g but without risk factors for heart failure. The primary endpoint is the time to onset of a >= 30% decrease in the eGFR or ESKD. Randomized patients (1:1) have been under treatment with once-daily oral bardoxolone methyl (5, 10 or 15 mg by intrapatient dose adjustment) or placebo for at least 3 years. Results The mean age of the 1013 patients is 65.9 years, 21.5% are female, the mean eGFR is 37.84 ml/min/1.73 m(2) and the median UACR is 351.80 mg/g. Conclusions Appropriate patients are enrolled in this study. This study will investigate the long-term efficacy and safety of bardoxolone methyl in DKD patients covering a wider range of eGFR (>= 15.0-<60.0 ml/min/1.73 m(2)) and albuminuria (<= 3500 mg/g) compared with previous studies.