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 angiotensin
II receptor blocker (ARB)for at least 6 weeks prior to and during screening. Stable
dose 2 weeks prior to and during screening. Patients not taking an ACE inhibitor
and/or ARB because of a medical contraindication must have discontinued treatment at
least 8 weeks prior to Screening Visit A;

5. Mean systolic blood pressure (SBP) must be ≤ 160 mmHg and ≥ 105 mmHg and mean
diastolic blood pressure (DBP) must be < 90 mm Hg during screening; both mean SBP and
mean DBP (determined as the average of three readings) must be within this range at
two 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) during
the entire study period and for at least 30 days after the last dose of the study
drug is ingested;

7. Serum magnesium level must be ≥ 1.3 mEq/L (0.65 mmol/L) at Screening Visit B or
during subsequent unscheduled visit during screening (serum magnesium level may be
re-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 provide
consent for access to medical data according to appropriate local data protection
legislation, allowing authorization to access medical records and describe events
captured in the endpoints

Exclusion Criteria:

1. Type 1 diabetes mellitus (juvenile onset). If a history of diabetic ketoacidosis
exists, a C-peptide level must confirm type 2 diabetes;

2. Known non-diabetic renal disease (e.g., polycystic kidney disease, focal segmental
glomerulosclerosis) [nephrosclerosis superimposed on diabetic kidney disease is
acceptable];

3. Ongoing clinical evidence suggesting non-diabetic renal disease other than
nephrosclerosis;

4. History of a renal transplant or a planned transplant from a living donor during the
study;

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 during
screening;

8. Clinical signs and/or symptoms of uremia and expected need for renal replacement
therapy 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 bypass
graft surgery, or percutaneous transluminal coronary angioplasty/stent within 12
weeks before study randomization; c. Cerebrovascular accident, including transient
ischemic attack within 12 weeks before study randomization; d. Current diagnosis of
Class III or IV New York Heart Association (NYHA) congestive heart failure;

10. Clinical diagnosis of severe obstructive valvular heart disease or severe obstructive
hypertrophic 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 prior
to study randomization or planned during the study;

13. Systemic immunosuppression for a total of > 2 weeks, cumulatively, within the 12
weeks prior 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 level
greater 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 are
nursing;

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 antibiotics
or 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-melanoma
skin cancer and carcinoma in situ of the cervix or a condition highly likely to
transform into malignancy during the course of the study;

22. A clinical condition that in the judgment of the investigator could potentially pose
a health risk to the patient while involved in the study;

23. Participation in a clinical study involving any intervention within 30 days prior to
randomization, concurrent participation in such a study, or participation in a prior
clinical 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.