Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria

A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study Evaluating the Safety and Efficacy of Oral GKT137831 in Patients With Type 2 Diabetes and Albuminuria

NADPH oxidase enzymes (NOX) have been implicated in the development of several diabetic complications including diabetic nephropathy. GKT137831 is the first in class NOX1/4 inhibitor.

The primary objective of this study is to evaluate the efficacy of oral GKT137831 in patients with residual albuminuria despite maximal inhibition of the renin angiotensin aldosterone system.

A double-blind, placebo-controlled, randomized, multicenter, parallel group Phase 2 study assessing a 12-week period of treatment with oral GKT137831 administered in addition to standard of care for patients with type 2 diabetes.

Key Inclusion Criteria:

• Male or female aged 18 to 80 years
• History of type 2 diabetes, defined as fasting plasma glucose ≥7.0 mmol/L (126 mg/dL) or a glycated hemoglobin (HbA1c) >6.5% (48 mmol/mol) on at least 2 occasions prior to screening.
• Albuminuria defined as a UACR of 300 to 3500 mg/g.
• An eGFR ≥30 mL/min/1.73 m2, as calculated by the CKD-EPI formula.
• Must be taking an ACEI or an ARB for at least 6 weeks prior to the first screening visit (Visit 1) and during the screening period. The dose must have been stable for at least 4 weeks prior to the first screening visit (Visit 1). Combination therapy associating an ACEI and an ARB is not permitted.

Key Exclusion Criteria:

• History of type 1 diabetes
• Any other non-diabetic kidney disease(s) except for hypertensive nephropathy which is acceptable.
• Diagnostic or interventional procedure requiring a contrast agent within 4 weeks of the first screening visit (Visit 1) or planned during the study.
• History of renal transplant or planned renal transplant during the study.
• A history of acute renal dialysis or acute kidney injury (defined according to the Kidney Disease: Improving Global Outcomes [KDIGO] definition) within 12 weeks of the first screening visit (Visit 1)
• HbA1c level >11% (97 mmol/mol).
• History of hypothyroidism requiring hormone replacement therapy.
• History of active cardiovascular disease
• A personal or family history of long QT syndrome.
• Administration of any investigational product within 30 days or within 5 half-lives of the investigational agent