• Part 1 - Maximum concentration (Cmax) of probe drugs co-administered with omaveloxolone (midazolam, repaglinide, metformin, rosuvastatin, and digoxin) [ Time Frame: 28 days ]
  Pharmacokinetics will be assessed by blood sampling for midazolam, repaglinide, metformin, rosuvastatin, and digoxin to determine maximum observed concentration (Cmax).
• Part 1 - Area under the plasma concentration-time curve of (AUC) for probe drugs co-administered with omaveloxolone (midazolam, repaglinide, metformin, rosuvastatin, and digoxin) [ Time Frame: 28 days ]
  Pharmacokinetics will be assessed by blood sampling for midazolam, repaglinide, metformin, rosuvastatin, and digoxin to determine area under the curve (AUC).
• Part 2 - Maximum concentration (Cmax) of omaveloxolone [ Time Frame: 23 days ]
  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).
• Part 2 - Area under the omaveloxolone concentration-time curve (AUC) [ Time Frame: 23 days ]
  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).
• Part 3 - Maximum concentration (Cmax) of omaveloxolone [ Time Frame: 23 days ]
  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).
• Part 3 - Area under the omaveloxolone concentration-time curve (AUC) [ Time Frame: 28 days ]
  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).
• Part 4 - Maximum concentration (Cmax) of omaveloxolone [ Time Frame: 23 days ]
  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).
• Part 4 - Area under the omaveloxolone concentration-time curve (AUC) [ Time Frame: 28 days ]
  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).

• Drug: Omaveloxolone
  50 mg capsules
  Other Name: RTA 408
• Drug: Midazolam oral solution
  2 mg/mL oral solution
• Drug: Repaglinide 1 MG
  1 mg tablet
• Drug: MetFORMIN 500 Mg Oral Tablet
  500 mg tablet
• Drug: Rosuvastatin
  10 mg tablet
• Drug: Digoxin tablet
  0.25 mg tablet
• Drug: Gemfibrozil Tablets
  600 mg tablet
• Drug: Itraconazole capsule
  100 mg capsule
• Drug: Verapamil Pill
  120 mg tablet

• Experimental: Omaveloxolone and Multiple Drugs (Part 1)
  Single oral doses of 2 mg midazolam, 1 mg repaglinide, 500 mg metformin, and a 10 mg rosuvastatin/0.25 mg digoxin cocktail on Days 1, 2, 3, and 5, respectively, and 18, 19, 20, and 22, respectively. Oral doses of 150 mg omaveloxolone on Days 12 to 27
  Interventions:

  • Drug: Omaveloxolone
  • Drug: Midazolam oral solution
  • Drug: Repaglinide 1 MG
  • Drug: MetFORMIN 500 Mg Oral Tablet
  • Drug: Rosuvastatin
  • Drug: Digoxin tablet
• Experimental: Omaveloxolone & Gemfibrozil (Part 2)
  Single oral doses of 150 mg omaveloxolone on Days 1 and 13. Oral doses of 600 mg gemfibrozil (twice daily) on Days 10 to 18
  Interventions:

  • Drug: Omaveloxolone
  • Drug: Gemfibrozil Tablets
• Experimental: Omaveloxolone and Itraconazole (Part 3)
  Single oral doses of 150 mg omaveloxolone on Days 1 and 13. Oral doses of 200 mg itraconazole on Days 10 to 18.
  Interventions:

  • Drug: Omaveloxolone
  • Drug: Itraconazole capsule
• Experimental: Omaveloxolone and Verapamil (Part 4)
  Single oral doses of 150 mg omaveloxolone on Days 1 and 13. Oral doses of 120 mg verapamil on Days 10 to 18.
  Interventions:

  • Drug: Omaveloxolone
  • Drug: Verapamil Pill

Inclusion Criteria:

Subjects must satisfy all of the following criteria at the Screening Visit unless otherwise stated:

• Males or females, of any race, between 18 and 55 years of age, inclusive.
• Body mass index between 18.0 and 32.0 kg/m2, inclusive, and a total body weight >50 kg.
• In good health.
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Exclusion Criteria:

Subjects will be excluded from the study if they satisfy any of the following criteria at the Screening visit, unless otherwise stated:

• Significant history or clinical manifestation of any major system disorder, as determined by the investigator (or designee).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (cholecystectomy will not be allowed; uncomplicated appendectomy and hernia repair will be allowed).
• History of alcoholism or drug/chemical abuse within 2 years prior to Check in (Day 1).
• Abnormal laboratory values considered clinically significant by the investigator
• Clinically significant abnormal 12 lead ECGs
• Personal history of unexplained syncopal events, or family history of long QT syndrome or sudden unexplained death in a young person.
• Pulse rate <50 bpm or systolic blood pressure <110 mmHg.
• Alcohol consumption of >21 units per week for males and >14 units for females.
• Positive urine drug screen or positive alcohol breath test result or positive urine drug screen.
• Positive hepatitis panel and/or positive human immunodeficiency virus test. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing or 5 half lives (if known), whichever is longer, prior to dosing.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing, unless deemed acceptable by the investigator (or designee).
• Have previously completed or withdrawn from this study or any other study investigating omaveloxolone, and have previously received the investigational product.
• Subjects who, in the opinion of the investigator (or designee), should not participate in this study.