Phase II Pharmacodynamic Trial to Determine the Effects of Bardoxolone Methyl on eGFR in Patients With Type 2 Diabetes and Chronic Kidney Disease

1. Any patient with Type 1 (insulin-dependent; juvenile onset) diabetes; or any history of diabetic ketoacidosis;

2. Any patient with known non-diabetic renal disease, family history of a hereditary form of kidney disease, or patients with a history of a renal transplant.

3. Any patient with clinical or renal biopsy evidence of any non-diabetic renal disease other than nephro-sclerosis;

4. Any patient with blood pressure (BP) that is unable to be controlled to a systolic pressure (SeSBP) \<160 mmHg and a diastolic pressure (SeDBP) of \<90 mmHg. BP will be determined by the average of 3 readings, taken after being seated for at least 5-minutes. BP must be within this range taken at 2 separate time-points at least 4 days apart during the screening period;

5. Any patient with Hemoglobin A1c level \>10% collected at screening;

6. Any patient with cardiovascular disease as follows:

1. Unstable angina pectoris within 3 months before study randomization;

2. Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 months before study randomization;

3. Transient ischemic attack within 3 months before study randomization;

4. Cerebrovascular accident within 3 months before study randomization;

5. Obstructive valvular heart disease or hypertrophic cardiomyopathy;

6. 2nd degree or 3rd degree atrioventricular block not successfully treated with a pacemaker;

7. Current diagnosis of Class III or IV congestive heart failure ;

7. Any patient with QTc Fredericia interval \> 450 milliseconds as determined by the average of values reported by a central reader from 3 ECGs taken at the Screening Visit.

8. Any patient with need for chronic (\>2 weeks) immunosuppressive therapy, including corticosteroids (excluding intra-articular injections inhaled or nasal steroids) within 3 months prior to randomization;

9. Any patient who requires more than occasional (once or twice weekly) use of non-steroidal anti-inflammatory agents (NSAIDS);

10. Any patient who requires a change or dose adjustment in any of the following medications: ACE inhibitors and ARBs within 8 weeks; other anti-hypertensive, and other anti-diabetic medications within 6 weeks prior to study randomization;

11. Any patient who is unable or unwilling to discontinue the following medications throughout the study period: Niacin® (nicotinic acid), Niaspan® (nicotinic acid), Niacor® (nicotinic acid), Nicolar® (nicotinic acid),Nicobid® (nicotinic acid), Nydrazid® (isoniazid), Dantrium® (dantrolene), Normodyne® (labetalol), Trandate® (labetalol), Cylert® (pemoline), Tradon® (pemoline), PemADD® (pemoline), Felbatol® (felbamate), Zyflo® (zileuton),Tasmar® (tolcapone), or Tricor® (fenofibrate), Antaram® (fenofibrate), Triglide® (fenofibrate), Lofibra® (fenofibrate), Lipidil Micro® (fenofibrate), Lipidil Supra® (fenofibrate); including fenofibrate derivatives e.g. Lopid® (gemfibrozil) and Atromid-S® (clofibrate) . Patient must discontinue the aforementioned medications for a minimum of two weeks prior to randomization. Patients may continue use of multi-vitamins (e.g., Centrum) ®, which have a maximum total daily consumption of \<= 50 mg of nicotinic acid (Niacin®);

12. Any patient with evidence of hepatic or biliary dysfunction including levels of total bilirubin \>1.0 mg/dL (\>17 micromole/L), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> upper limit of normal (ULN), or alkaline phosphatase \>2.0 times the ULN on ANY screening laboratory test result;

13. If a patient provides a history of hepatitis B or C but has normal liver enzyme levels, the investigator should perform a serologic hepatitis screen and call the Medical Monitor to discuss patient eligibility. Patients with a history of hepatitis A that is resolved and who do not demonstrate any liver enzyme level elevation are eligible for protocol randomization;

14. Any female patient who is pregnant, nursing or planning a pregnancy;

15. Any patient with known hypersensitivity to any component of the study drug;

16. Any patient who has undergone diagnostic or intervention procedure requiring a contrast agent within the last 30 days prior to study randomization;

17. Patient with a current history of drug or alcohol abuse as per the Investigator's assessment;

18. Any patient with a history of neoplastic disease (except basal or squamous cell carcinoma of the skin) within 5 years prior to study randomization;

19. Any patient who has had dialysis within 3 months before randomization and/or have not maintained a stable level of kidney function within 3 months of randomization per Investigator assessment;

20. Any patient who has any concurrent clinical conditions that in the judgment of the investigator could either potentially pose a health risk to the patient while involved in the study or could potentially influence the study outcome;

21. Any patient who has participated in another clinical study involving investigational or marketed products within 30 days prior to randomization or would concomitantly participate in such a study, or any patient who has received bardoxolone methyl in any form;

22. Any patient who is unable to communicate or cooperate with the Investigator due to language problems, poor mental development, or impaired cerebral function.

What this study is about