Effect of Itraconazole on the Pharmacokinetics of Bardoxolone Methyl in Healthy Adults

Inclusion Criteria:

- Male or female and age is between 18 and 55 years, inclusive;

- Female subjects of childbearing potential must not be planning a pregnancy, pregnant,
or lactating, and must have a negative serum pregnancy test result before enrollment
into the study, and must be willing to use contraception as specified or abstain from
sexual activity for the duration of the study;

- If male, subject must be surgically sterile or practicing an approved method of
contraception, from initial study drug administration through 90 days after
administration of the last dose of study drug;

- If male, subject agrees to abstain from sperm donation through 90 days after
administration of the last dose of study drug;

- Body Mass Index (BMI) is ≥ 18 to ≤31 kg/m2, inclusive;

- A condition of general good health, based upon the results of a medical history,
physical examination, vital signs, laboratory profile, and a 12-lead electrocardiogram
(ECG), as judged by the investigator;

- Must voluntarily sign and date each informed consent, approved by an Institutional
Review Board (IRB), prior to the initiation of any screening or study-specific
procedures.

Exclusion Criteria:

- History of clinically significant drug allergies, including allergies to any of the
components of the investigational product and/or clinically significant food allergies
as determined by the investigator;

- Presence or history of any significant cardiovascular, gastrointestinal, hepatic,
renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, or
psychiatric disease, as determined by the investigator;

- Presence of any other condition (including surgery) known to interfere with the
absorption, distribution, metabolism, or excretion of medicines;

- Known hypersensitivity to any component in the formulations of bardoxolone methyl, or
SPORANOX®;

- Requirement for any over-the-counter and/or prescription medication, vitamins, and/or
herbal supplements on a regular basis;

- Use of any medications (over-the-counter and/or prescription medication), vitamins,
and/or herbal supplements, within the 30-day period prior to study drug administration
or within 5 half-lives (if known), whichever is longer;

- Recent (6-month) history of drug or alcohol abuse;

- B-type natriuretic peptide (BNP) level >200 pg/mL at screening;

- Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus
antibody (HCV Ab), or HIV antibodies (HIV Ab) at screening;

- Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt
of a transfusion of any blood product within 8 weeks prior to study drug
administration;

- Receipt of any investigational product within a time period equal to 10 half-lives of
the product, if known, or a minimum of 30 days prior to study drug administration;

- Positive screen results for drugs of abuse, alcohol, or cotinine at screening or Day
-1;

- Consumption of alcohol within 72 hours prior to study drug administration;

- Consumption of grapefruit, grapefruit products, star fruit, star fruit products, or
Seville oranges within the 72-hour period prior to study drug administration;

- Use of tobacco or nicotine-containing products within the 6-month period preceding
study drug administration;

- Current enrollment in another clinical study;

- Screening laboratory analyses that show any of the following abnormal laboratory
results:

1. Alanine transaminase (ALT) or aspartate aminotransferase (AST) levels above the
upper limit of normal (ULN);

2. Clinically significant abnormal ECG; ECG with QTc using Fridericia's correction
formula (QTcF) > 450 msec is exclusionary;

3. Consideration by the investigator, for any reason, that the subject is an
unsuitable candidate to receive either bardoxolone methyl or itraconazole.