| Eligibility |
Inclusion Criteria:
- Screening eGFR = 30.0 and < 60.0 mL/min/1.73 m2;
- A history of type 2 diabetes; diagnosis should have been made at = 30 years of age (if
diabetes developed at a younger age, a fasting C-peptide level must be = 0.1 ng/mL to
confirm type 2 diabetes);
- Male or female patients at least 18 years of age;
- 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 and during
screening. The dosage of ACE inhibitor and/or ARB must be stable for 2 weeks prior to
Screening Visit A and during screening (i.e., no change in dosage or medication).
Patients not taking an ACE inhibitor and/or ARB, or taking an ACE inhibitor and/or ARB
at levels below the goal dose set by K/DOQI guidelines (See Appendix 3) should have a
documented medical contraindication (e.g., hyperkalemia, dry cough, angioedema), which
the investigator must discuss with the appropriate medical monitor;
- Albumin/creatinine ratio (ACR) < 300 mg/g;
- Mean systolic blood pressure (SBP) must be = 160 mmHg and = 105 mmHg and mean
diastolic blood pressure (DBP) must be < 90 mmHg during screening; both mean SBP and
mean DBP (determined as the average of three readings) must be within the described
range;
- Willing to practice methods of birth control (both males who have partners of
childbearing potential and females of childbearing potential, [see Section 9.7])
during screening, while taking study drug and for at least 30 days after the last dose
of study drug is ingested;
- Willing and able to cooperate with all aspects of the protocol;
- 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 that describe events
captured in the endpoints.
Exclusion Criteria:
- Type 1 diabetes mellitus (juvenile onset). If a history of diabetic ketoacidosis
exists, a C-peptide level must confirm type 2 diabetes;
- Known non-diabetic renal disease (e.g., known polycystic kidney disease or family
history of a hereditary form of kidney disease) [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;
- History of a renal donation, transplant or a planned transplant from a living donor
during the study;
- Hemoglobin A1c level > 9.0% (75 mmol/mol) during screening;
- Acute dialysis or acute kidney injury within 12 weeks prior to screening or during
screening;
- Clinical signs and/or symptoms of uremia and expected need for renal replacement
therapy within 12 weeks following randomization, as assessed by the investigator;
- 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 4);
- Clinical diagnosis of severe obstructive valvular heart disease or severe obstructive
hypertrophic cardiomyopathy;
- Atrioventricular block, 2o or 3o, not successfully treated with a pacemaker;
- Diagnostic or interventional procedure that required a contrast agent within 30 days
prior to baseline mGFR visit 1 or planned during the study;
- Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks
prior to randomization or anticipated need for immunosuppression during the study;
- 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;
- Female patients who are pregnant, intend to become pregnant during the study, or are
nursing;
- BMI < 18.5 kg/m2;
- Known hypersensitivity to any component of the study drug;
- Current history of drug or alcohol abuse, as assessed by the investigator;
- Clinically significant infection requiring intravenous administration of antibiotics
or hospitalization within 6 weeks prior to Screening Visit or during screening;
- Diagnosis or treatment of a malignancy in the past 5 years, excluding non-melanoma
skin cancer and carcinoma in situ of the cervix;
- A clinical condition that, in the judgment of the investigator, could potentially pose
a health risk to the patient while involved in the study;
- Unable to communicate or cooperate with the investigator due to language problems,
poor mental development, or impaired cerebral function;
- 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.
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