A MULTIPLE-DOSE, OPEN-LABEL PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF BARDOXOLONE METHYL IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND TYPE 2 DIABETES
This study is a multiple-dose, open-label pharmacokinetic (PK) and pharmacodynamic (PD) study in patients with CKD and type 2 diabetes. Patients will complete a screening visit prior to Study Day -1. Patients that qualify for the study based on inclusion/exclusion criteria will receive 20 mg bardoxolone methyl once daily under fasting conditions from Study Day 1 through Day 56. Patients will be present at the clinical unit for intensive PK/PD sampling on Study Day -1 through Study Day 2 and Study Day 56 through Study Day 60. Patients will return to the clinic on Days 28 and 42 to provide trough PK samples. Patients will be monitored after study drug discontinuation with a study visit on Day 84.
1.Screening eGFR ≥15.0 and < 45.0 mL/min/1.73 m2.
2.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 confirm type 2 diabetes);
3.Male or female patients at least 18 years of age;
4.Body mass index (BMI) between 18.5 and 45 kg/m2;
5.Treatment with an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) for at least 6 weeks prior to Study Day -1. The dosage of ACE inhibitor and/or ARB must be stable for 2 weeks prior to 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 A) must have a documented medical contraindication (e.g., hyperkalemia, hypotension), which the investigator must provide and discuss with a medical monitor prior to Study Day -1. Patients not taking an ACE inhibitor and/or ARB because of a medical contraindication must have discontinued treatment at least 8 weeks prior to Screening;
6.Mean systolic blood pressure (SBP) must be ≤ 160 mmHg and ≥ 105 mmHg and mean diastolic blood pressure (DBP) must be ≤ 90 mmHg during screening;
7.Willing to practice methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) from screening through Study Day 84;
8.Female patients of childbearing potential must be non-pregnant and non-lactating and have a negative serum pregnancy test result prior to enrollment in the study;
9.Willing and able to give written informed consent for study participation;
10.Willing and able to cooperate with all aspects of the protocol;