Single-Dose, Open-Label Pharmacokinetic Study of Bardoxolone Methyl in Subjects With Mild, Moderate, and Severe Hepatic Impairment and Normal Hepatic Function

Inclusion Criteria:

- All subjects

1. Male or female subjects between 18 and 70 years, inclusive; must meet all of the
following criteria to be included in the study:

2. Willing to practice method 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;

3. Female subjects of childbearing potential must be non-pregnant and non-lactating
and have a negative serum pregnancy test result before enrollment into the
study;

4. Body mass index (BMI) between 18 and 37 kg/m2;

5. Willing and able to give written informed consent for study participation;

6. Willing and able to cooperate with all aspects of the protocol.

Subjects with hepatic impairment

7. Have documented evidence of hepatic cirrhosis by biopsy, nuclear scan, CT, MRI,
ultrasound, or other clinically acceptable methods; must meet all of the
following criteria to be included in the study:

8. Be classified as Child-Pugh class A (mild), B (moderate), or C (severe). (See
Appendix A for Child-Pugh system.)

Exclusion Criteria:

- All subjects

1. Participated in another clinical trial of an investigational drug (or a medical
device) within 30 days of Study Day -1, or are currently participating in
another trial of an investigational drug (or a medical device); with any of the
following conditions or characteristics must be excluded from the study:

2. Known hypersensitivity to any component in the formulation of the study drug,
bardoxolone methyl;

3. Any medical or dental procedure, no matter how minor, that is planned or
anticipated to occur during the conduct of the study;

4. History of drug or alcohol abuse or dependence within the last year;

5. Donation or receipt of blood or blood components within the 4 weeks prior to
Study Day -1. The investigator should instruct subjects who participate in this
study not to donate blood or blood components for 4 weeks after the completion
of the study;

6. Abnormal screening ECG which is interpreted by the investigator to be clinically
significant;

7. A positive test for drug(s) of abuse (ethanol, amphetamines, benzodiazepines,
barbiturates, cocaine, opiates, or cannabinoids) at the screening or the Day -1
visit, unless the positive drug screen is for a subject with hepatic impairment
for a prescription drug and is approved by the principal investigator;

8. Female subjects who are planning a pregnancy or are pregnant or lactating;

9. Deemed by the investigator to be inappropriate for this study, including
subjects who are unable to communicate with the investigator due to language
problems, poor mental development, or impaired cerebral function;

10. Any concurrent clinical conditions that in the judgment of the investigator
could either potentially pose a health risk to the subject while involved in the
study or could potentially influence the study outcome;

11. Positive test results for human immunodeficiency virus type 1 or 2 antibody at
screening;

12. Have an estimated creatinine clearance < 60 mL/min on Study Day -1 using the
Cockcroft-Gault equation (Appendix B);

13. Any condition possibly affecting absorption, distribution, metabolism or
excretion of drugs that may confound the analyses conducted in this study (for
example: previous surgery on the gastrointestinal tract that includes removal of
parts of stomach, bowel, liver, gall bladder, pancreas, venacaval shunts, or
transjugular intrahepatic portosystemic shunts]).

Subjects with hepatic impairment

14. Sustained systolic blood pressure > 160 mmHg or < 100 mmHg or a diastolic blood
pressure > 100 mmHg at screening or baseline measured after 5 minutes in a
sitting position; who have any of the following conditions or characteristics
must be excluded from the study:

15. A pulse rate at rest in a sitting position of < 45 bpm or > 105 bpm;

16. Documented evidence of primary biliary cirrhosis;

17. Evidence of recent (two months or less) or current gastrointestinal bleeding;

18. Platelet counts <50,000 or >450,000.

Subjects with normal hepatic function

19. Sustained systolic blood pressure > 150 mmHg or < 100 mmHg or a diastolic blood
pressure > 95 mmHg at screening measured after 5 minutes in a sitting position;
who have any of the following conditions or characteristics must be excluded
from the study:

20. A pulse rate at rest in a sitting position of < 45 bpm or > 100 bpm;

21. Evidence or history of or concurrent clinically significant allergic (except for
untreated, asymptomatic, seasonal allergies at time of dose administration),
hematological, endocrine, immunological, renal, pulmonary, gastrointestinal,
cardiovascular, hepatic, psychiatric, or neurological disease that in the
judgment of the investigator could potentially either pose a health risk to the
subject during the study or influence the study outcome;

22. Evidence of hepatic or biliary dysfunction including elevation of total
bilirubin, direct bilirubin, aspartate aminotransferase (AST), alanine
aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), lactate
dehydrogenase (LDH), or alkaline phosphatase levels to greater than the upper
limit of normal (ULN);

23. Positive test results for hepatitis B virus antibody, or hepatitis C virus
antibody at screening;

24. Use of or need for any systemic drug(s) including vitamins or herbal
preparations other than drugs used for contraception, within 10 days before
Study Day -1 or during the study;

25. Use of aspirin, non-steroidal anti-inflammatory agents, or acetaminophen within
5 days prior to the ingestion of the study drug; use of aspirin or non-steroidal
anti inflammatory agents (but not acetaminophen) will be allowed for isolated
episodes of pain at the discretion of the investigator.