A food effect study and dose proportionality study to assess the pharmacokinetics and safety of bardoxolone methyl in healthy volunteers

• Published in: Clinical pharmacology in drug development 2014-07, Vol.3 (4), p.314-320
• Main Authors: Teuscher, Nathan S., Kelley, Richard J., Dumas, Emily O., Klein, Cheri Enders, Awni, Walid M., Meyer, Colin J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - blood; Anti-Inflammatory Agents - pharmacokinetics; Antioxidants - administration & dosage; Antioxidants - adverse effects; Antioxidants - pharmacokinetics; bardoxolone methyl; Drug Monitoring; Fasting - blood; Female; food effect; Food-Drug Interactions; Healthy Volunteers; Humans; Male; Middle Aged; Models, Biological; Oleanolic Acid - administration & dosage; Oleanolic Acid - adverse effects; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - blood; Oleanolic Acid - pharmacokinetics; pharmacokinetics; Postprandial Period; Risk Assessment; Wisconsin; Young Adult
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.74

This study investigated the effect of food on the plasma pharmacokinetics of bardoxolone methyl, an antioxidant inflammation modulator, at a 20 mg dose, and the dose proportionality of bardoxolone methyl pharmacokinetics from 20 to 80 mg. It was a single‐dose study conducted at a single center in 32 healthy volunteers aged 18–45 years using an amorphous spray‐dried dispersion formulation of bardoxolone methyl. In Part A, 16 subjects received single 20 mg doses of bardoxolone methyl under fasting and non‐fasting conditions. In Part B, 16 subjects received a single 60 or 80 mg dose of bardoxolone methyl and a matching placebo dose under fasting conditions. Blood samples for pharmacokinetic analysis were taken over 120 hours following dose administration. Single dose administration of 20, 60, and 80 mg bardoxolone methyl was safe and well‐tolerated in healthy volunteers. Total bardoxolone methyl exposure was unchanged in the presence of food. However, doses of bardoxolone methyl above 20 mg appear to have a saturated dissolution or absorption process and are associated with less than proportional increases in drug exposure.