Primary Outcome Measures:
- To determine the effects of RTA 402 administered orally at three dose strengths on the glomerular filtration rate (as estimated by the MDRD formula) in patients with diabetic nephropathy.
Secondary Outcome Measures:
- To evaluate the safety and tolerability of oral RTA 402 administered orally at three different doses in this patient population.
- To evaluate the effects of RTA 402 administered orally at three dose strengths on the serum creatinine level, iohexol serum clearance (one study center only), creatinine clearance, and urine albumin/creatinine ratio in patients with diabetic nephropathy.
- To evaluate the effects of RTA 402 administered orally at three dose strengths on hemoglobin A1c in all patients enrolled and on insulin response by the hyperinsulinemic euglycemic clamp test in patients enrolled at only one of the study centers.
- To evaluate the effects of RTA 402 at three different doses on a panel of markers of inflammation, renal injury, oxidative stress, and endothelial cell dysfunction.
Bardoxolone is an Antioxidant Inflammation Modulator (AIM) in clinical development for inflammation and cancer-related indications that inhibits immune-mediated inflammation by restoring redox homeostasis in inflamed tissues. It induces the cytoprotective transcription factor Nrf2 and suppresses the activities of the pro-oxidant and pro-inflammatory transcription factors NF-kB and the STATs. In vivo, bardoxolone has demonstrated significant single agent anti-inflammatory activity in several animal models of inflammation such as renal damage in the cisplatin model and ischemia-reperfusion model of acute renal injury. In addition, significant reductions in serum creatinine have been observed in patients treated with bardoxolone. Based on these data, it is hypothesized that bardoxolone can improve renal function in patients with diabetic nephropathy through suppression of renal inflammation and improvement of glomerular filtration.