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:

• Alanine transaminase (ALT) or aspartate aminotransferase (AST) levels above the upper limit of normal (ULN);
• Clinically significant abnormal ECG; ECG with QTc using Fridericia's correction formula (QTcF) > 450 msec is exclusionary;
• Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive either bardoxolone methyl or itraconazole.