Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes

Inclusion Criteria:

1. Screening eGFR ≥ 15.0 and < 30.0 mL/min/1.73 m2;
2. A history of type 2 diabetes; diagnosis should have been made at ≥ 30 years of age;
3. Male or female at least 18 years of age;
4. Treatment with an angiotensin converting enzyme (ACE)inhibitor and/or an angiotensinII receptor blocker (ARB)for at least 6 weeks prior to and during screening. Stabledose 2 weeks prior to and during screening. Patients not taking an ACE inhibitorand/or ARB because of a medical contraindication must have discontinued treatment atleast 8 weeks prior to Screening Visit A;
5. Mean systolic blood pressure (SBP) must be ≤ 160 mmHg and ≥ 105 mmHg and meandiastolic blood pressure (DBP) must be < 90 mm Hg during screening; both mean SBP andmean DBP (determined as the average of three readings) must be within this range attwo separate time points measured at least 4 days apart during the screening period (blood pressure may be re-evaluated once during an unscheduled visit);
6. Willing to practice methods of birth control (both male and female patients) duringthe entire study period and for at least 30 days after the last dose of the study drugis ingested;
7. Serum magnesium level must be ≥ 1.3 mEq/L (0.65 mmol/L) at Screening Visit B or duringsubsequent unscheduled visit during screening (serum magnesium level may bere-evaluated once during an unscheduled visit);
8. Willing and able to cooperate with all aspects of the protocol;
9. Willing and able to give written informed consent for study participation and provideconsent for access to medical data according to appropriate local data protectionlegislation, allowing authorization to access medical records and describe eventscaptured in the endpoints

Exclusion Criteria:

1. Type 1 diabetes mellitus (juvenile onset). If a history of diabetic ketoacidosisexists, a C-peptide level must confirm type 2 diabetes;
2. Known non-diabetic renal disease (e.g., polycystic kidney disease, focal segmentalglomerulosclerosis) [nephrosclerosis superimposed on diabetic kidney disease isacceptable];
3. Ongoing clinical evidence suggesting non-diabetic renal disease other thannephrosclerosis;
4. History of a renal transplant or a planned transplant from a living donor during thestudy;
5. Albumin to creatinine ratio (ACR) greater than 3500 mg/g (395.5 mg/mmol);
6. Hemoglobin A1c level > 11.0% (97 mmol/mol) during screening;
7. Acute dialysis or acute kidney injury within 12 weeks prior to screening or duringscreening;
8. Clinical signs and/or symptoms of uremia and expected need for renal replacementtherapy within 12 weeks following randomization, as assessed by the investigator;
9. Recently active cardiovascular disease defined as: a. Unstable angina pectoris within 12 weeks before study randomization; b. Myocardial infarction, coronary artery bypassgraft surgery, or percutaneous transluminal coronary angioplasty/stent within 12 weeksbefore study randomization; c. Cerebrovascular accident, including transient ischemicattack within 12 weeks before study randomization; d. Current diagnosis of Class IIIor IV New York Heart Association (NYHA) congestive heart failure;
10. Clinical diagnosis of severe obstructive valvular heart disease or severe obstructivehypertrophic cardiomyopathy;
11. Atrioventricular block, 2o or 3o, not successfully treated with a pacemaker;
12. DAdministration of a contrast agent that may induce nephropathy within 30 days priorto study randomization or planned during the study;
13. Systemic immunosuppression for a total of > 2 weeks, cumulatively, within the 12 weeksprior to randomization or planned during the study;
14. Total bilirubin, aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT)levels greater than the upper limit of normal (ULN), or alkaline phosphatase levelgreater than two times the ULN on ANY screening laboratory test result;
15. Female patients who are pregnant, intend to become pregnant during the study, or arenursing;
16. BMI < 18.5 g/m2
17. Known hypersensitivity to any component of the study drug;
18. Current history of drug or alcohol abuse as assessed by the investigator;
19. Clinically significant infection requiring intravenous administration of antibioticsor hospitalization within 6 weeks of screening or during screening;
20. Hepatitis B surface antigen positive;
21. Diagnosis or treatment of a malignancy in the past 5 years, excluding non-melanomaskin cancer and carcinoma in situ of the cervix or a condition highly likely totransform into malignancy during the course of the study;
22. A clinical condition that in the judgment of the investigator could potentially pose ahealth risk to the patient while involved in the study;
23. Participation in a clinical study involving any intervention within 30 days prior torandomization, concurrent participation in such a study, or participation in a priorclinical study involving bardoxolone methyl in any form;
24. Unable to communicate or cooperate with the investigator due to language problems,poor mental development or impaired cerebral function.