| Eligibility |
Inclusion Criteria:
1. Patients must have a history of 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. Patients must be at least 18 years of age;
3. The average of 2 eGFR values collected during screening must be within 15 - 45 mL
/min/1.73m2 inclusive.
4. Patients must be receiving an angiotensin converting enzyme (ACE) inhibitor and/or an
angiotensin II receptor blocker (ARB) for at least 8 weeks prior to screening, where
the dose of the ACE inhibitor or the ARB is considered appropriate for that patient,
and the patient has been stable and maintained on that dose for at least 8 weeks prior
to randomization (Day 1). No change in ACE or ARB therapy should be anticipated or
planned for the period of the study.
5. Male and female patients must agree 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
6. Women of child-bearing potential must have a negative serum pregnancy test result at
screening and a confirmed negative urine pregnancy test result prior to administration
of the first dose of study medication;
7. Patient is willing and able to cooperate with all aspects of the protocol;
8. Patient is willing and able to give written informed consent for study participation
Exclusion Criteria:
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.
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