| Eligibility |
Inclusion Criteria:
1. Male or female patient, at least 18 years of age with known type 2 diabetes, diagnosis
of type 2 diabetes should have been made at > 30 years of age (if diabetes developed
at a younger age, C-peptide level may be obtained to confirm diagnosis)
2. The average of two eGFR values collected during screening must be within 20 - 45
mL/min/1.73m2, inclusive
3. Patient must be receiving an angiotensin converting enzyme (ACE) inhibitor and/or an
angiotensin II receptor blocker (ARB) for at least 3 months prior to screening, where
the dose of the ACE inhibitor or the ARB is considered appropriate for that patient,
and has been stable and maintained on that dose for at least 8 weeks prior to the
Randomization visit
4. For male and female subjects, agreement to use effective contraception during the
entire study period and for at least 2 months after the last dose of study drug,
unless documentation of infertility exists
5. Women of child-bearing potential, she must have a negative serum pregnancy test at
screening and a negative urine pregnancy test confirmed within 72 hours prior to the
first dose of study medication
6. Patient is willing and able to cooperate with all aspects of the protocol
7. Patient is willing and able to give written informed consent for study participation.
Exclusion Criteria:
1. Type 1 (insulin-dependent; juvenile onset) diabetes, or any history of diabetic
ketoacidosis
2. Patients with known non-diabetic renal disease or patients with a history of a renal
transplant
3. Patients with a Hemoglobin A1c >10% collected at the Screening A visit
4. Cardiovascular disease as follows: Unstable angina pectoris within 3 months prior to
study randomization; Myocardial infarction, coronary artery bypass graft surgery, or
percutaneous transluminal coronary angioplasty/stent within 3 months prior to study
randomization; Transient ischemic attack within 3 months of study randomization;
Cerebrovascular accident within 3 months of study randomization; Obstructive valvular
heart disease or hypertrophic cardiomyopathy; Diagnosis of Class III or IV congestive
heart failure at any time
5. Systolic blood pressure (BP) >160 mmHg and diastolic blood pressure > 90 determined by
the average of three seated readings taken at least 5 minutes apart, at each of two
time-points at least 5 days apart during the screening period
6. QTc Fredericia interval > 450 milliseconds determined by the average of values
reported by a central reader from three ECGs taken at the Screening A visit. Each of
the three ECGs will be obtained using only equipment provided by the Sponsor, and the
ECGs shall be obtained at least ten minutes apart.
7. Second or third degree atrioventricular block not successfully treated with a
pacemaker
8. Need for chronic (>2 weeks) immunosuppressive therapy, or need for corticosteroids
(excluding intraarticular injections,inhaled or nasal steroids) within 3 months of
study randomization
9. Evidence of hepatic or biliary dysfunction including total bilirubin >1.0 mg/dL (>17
micromol/L), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >
upper limit of normal (ULN), or alkaline phosphatase >2.0 ULN on ANY screening lab
10. If female, patient is pregnant, nursing or planning a pregnancy
11. Patient 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
12. Patient has known hypersensitivity to any component of the study drug
13. Patient has undergone a diagnostic or interventional procedure requiring a contrast
agent within 30 days prior to randomization
14. Change or dose adjustment in any of the following medications within 8 weeks prior to
randomization into the study or anticipated change in dose within 30 days following
randomization into the study: ACE inhibitors, angiotensin II receptor blockers.
15. Change or dose adjustment of any other anti-hypertensive, and other anti-diabetic
medications within 8 weeks prior to randomization or anticipated change in dose within
30 days following randomization into the study
16. Patient has a current history of drug or alcohol abuse as per the investigator's
assessment
17. Patient has participated in another investigational study within 30 days prior to
randomization into the study or would concomitantly participate in such a study, or
has previously participated in a trial involving bardoxolone methyl.
18. Patient is unable to communicate or cooperate with the investigator due to language
problems, poor mental development or impaired cerebral function
19. Patient is unable or unwilling to utilize the daily phone diary to track the date and
time they take their study medication
20. Patients on any of the following known hepatotoxic agents: Antioxidant
N-acetly-cysteine (Mucomyst, Acetadote, Fluimucil, Parvolex), Niacin (nicotinic acid),
Dantrium (dantrolene), Naizide (isoniazid), Normodyne (labetalol), Cylert (pemoline),
Felbatol (felbamate), Zyflo (zileuton), Tasmar (tolcapone), or Trovan (trovafloxacin).
Patients must have been off the aforementioned medications for a minimum of two weeks
prior to randomization
21. Patients who are unable or unwilling to discontinue fenofibrate (Antara, Fenoglide,
Lipofen, Lofibra, TriCor, Triglide) during the first three months of study treatment.
Patients must have been off fenofibrate for a minimum of two weeks prior to
randomization
22. Patients who require more than occasional (once or twice weekly) use of non-steroidal
anti-inflammatory agents (NSAIDS)
23. Patients with a history of neoplastic disease (except basal or squamous cell carcinoma
of the skin) within 5 years prior to the randomization visit;
24. Patients who have had prior dialysis within three months of randomization and/or have
not maintained a stable level of kidney function within three months of randomization
per Investigator assessment
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