A Clinical Drug-Drug Interaction (DDI) Study With Omaveloxolone

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

Primary outcomes

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

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

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.

• Jennifer Zon, MD, Principal investigator, Covance CRU Inc.