An Exploratory Randomized Trial of SCO-792, an Enteropeptidase Inhibitor, in Patients With Type 2 Diabetes and Albuminuria.

ABSTRACT

Introduction: Elevated plasma amino acid levels overload kidney function by increasing glomerular filtration rate (GFR). Inhibiting gut amino acid intake may have therapeutic benefits for patients with kidney dysfunction. For a prospective phase 2a trial, we carried out an exploratory evaluation of the safety and efficacy of SCO-792, an enteropeptidase inhibitor that blocks gut amino acid intake, in patients with type 2 diabetes mellitus (T2DM) and albuminuria. Methods: Seventy-two patients with T2DM, a urine albumin-to-creatinine ratio (UACR) of 200-5000 mg/g, and an estimated GFR >30 ml/min per 1.73 m2 were included. Patients were randomly assigned (122) to the following groups and received treatment for 12 weeks placebo (n = 15), SCO-792 500 mg once daily (SCO-792 QD; n = 29), or SCO-792 500 mg 3 times daily (SCO-792 3 times a day (TID); n = 28) by following a double-blind approach. We evaluated UACR changes from the baseline along with safety as the primary end points and other parameters as secondary or exploratory end points. Results: SCO-792 was safe and well tolerated up to 1500 mg/day for 12 weeks. UACR changes from baseline were -14% (P = 0.4407), -27% (P = 0.0271), and -28% (P = 0.0211) in placebo, SCO-792 QD, and SCO-792 TID, respectively, whereas UACR changes in SCO-792 groups were not statistically significant compared with placebo. The hemoglobin A1c (HbA1c) levels from baseline, an exploratory end point, decreased in the SCO-792 TID group. Conclusion: SCO-792 was safe and well tolerated for 12 weeks and may be associated with decreased UACR in patients with T2DM and albuminuria. Further clinical studies are essential to confirm our findings.