| Eligibility |
Inclusion Criteria:
1. Screening eGFR = 15.0 and < 30.0 mL/min/1.73 m2; screening eGFR will be the average of
the eGFR values collected during screening;
2. A history of type 2 diabetes mellitus; diagnosis must have been made at = 30 years of
age;
3. Male or female patients at least 30 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 Screening Visit A and during
screening. The dosage of ACE inhibitor and/or ARB must be at KDOQI goal dose (Appendix
13.4) and stable for 2 weeks prior to Screening Visit A and during screening (i.e., no
change in dosage or medication);
5. Mean systolic blood pressure (SBP) must be = 160 mmHg and = 105 mmHg and mean
diastolic blood pressure (DBP) must be < 90 mmHg during screening visits A and B;
6. Willing to practice methods of birth control (both males who have partners of
childbearing potential and females of childbearing potential) during screening, while
taking study drug and for at least 30 days after the last dose of study drug is
ingested;
7. Serum magnesium level must be greater than or equal to 1.3 mEq/L at Screening Visit B
or during a subsequent unscheduled visit during screening (serum magnesium level may
be re-evaluated once during an unscheduled visit);
8. Willing and able to give written informed consent for study participation and
cooperate with all aspects of the protocol including tolerating being in a closed MRI.
Exclusion Criteria:
Type 1 diabetes mellitus. If a history of diabetic ketoacidosis exists, a fasting 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]; Ongoing clinical investigation with evidence (e.g.,
unexplained hematuria or red blood cell or white blood cell casts) 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. Urine albumin/creatinine ratio (UACR)
at Screening Visit B greater than 3500 mg/g; 6. Hemoglobin A1c level > 11.0% 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:
- Unstable angina pectoris within 12 weeks before study randomization;
- Myocardial infarction, coronary artery bypass graft surgery, or percutaneous
transluminal coronary angioplasty/stent within 12 weeks before study randomization;
- Cerebrovascular accident, including transient ischemic attack, within 12 weeks before
study randomization;
- Current diagnosis of Class III or IV NYHA congestive heart failure (Appendix 13.3);
10. Clinical diagnosis of severe obstructive valvular heart disease or severe
obstructive hypertrophic cardiomyopathy; 11. Atrioventricular block, 20 or 30; 12.
Implanted medical device that would prevent obtaining a MRI; 13. Administration of a
contrast agent that may induce nephropathy within 30 days prior to study randomization
or planned during the study; 14. Systemic immunosuppression for more than 2 weeks,
cumulatively, within the 12 weeks prior to randomization or anticipated need for
immunosuppression during the study; 15. Total bilirubin, aspartate transaminase (AST),
or alanine transaminase (ALT) level greater than the upper limit of normal (ULN) or
alkaline phosphatase level greater than two times the ULN on ANY screening laboratory
test result; 16. Female patients who are pregnant, intend to become pregnant during
the study, or are nursing; 17. BMI < 18.5 kg/m2; 18. Weight = 300 pounds; 19. Height >
6'3"; 20. Partial or total amputation of a lower extremity prior to randomization; 21.
Known hypersensitivity to any component of the study drug; 22. Current history of drug
or alcohol abuse, as assessed by the investigator; 23. Clinically significant
infection requiring intravenous administration of antibiotics or hospitalization
within 6 weeks prior to Screening Visit A or during screening; 24. Hepatitis B surface
antigen positive; 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 a malignancy during the course of the study; 26.
History of bariatric surgery or planned bariatric surgery during the course of the
study; 27. A clinical condition that, in the judgment of the investigator, could
potentially pose a health risk to the patient while involved in the study; 28.
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; 29. Unable to communicate or
cooperate with the investigator due to language problems, poor mental development, or
impaired cerebral function.
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