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

NCT04008186 | Completed Phase 1 FDA Drug

• 1 other identifier: 408-C-1806
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the potential for clinical drug-drug interactions between omaveloxolone and a number of substrates and inhibitors of metabolic enzymes and drug transporters.

Conditions

Healthy Adult Subjects

Keywords

RTA 408; RTA 408 capsules; omaveloxolone; omaveloxolone capsules; DDI

Outcome Measures

Primary Outcomes (8)

• Part 1 - Maximum concentration (Cmax) of probe drugs co-administered with omaveloxolone (midazolam, repaglinide, metformin, rosuvastatin, and digoxin)

  Pharmacokinetics will be assessed by blood sampling for midazolam, repaglinide, metformin, rosuvastatin, and digoxin to determine maximum observed concentration (Cmax).

  28 days

• Part 1 - Area under the plasma concentration-time curve of (AUC) for probe drugs co-administered with omaveloxolone (midazolam, repaglinide, metformin, rosuvastatin, and digoxin)

  Pharmacokinetics will be assessed by blood sampling for midazolam, repaglinide, metformin, rosuvastatin, and digoxin to determine area under the curve (AUC).

  28 days

• Part 2 - Maximum concentration (Cmax) of omaveloxolone

  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).

  23 days

• Part 2 - Area under the omaveloxolone concentration-time curve (AUC)

  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).

  23 days

• Part 3 - Maximum concentration (Cmax) of omaveloxolone

  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).

  23 days

• Part 3 - Area under the omaveloxolone concentration-time curve (AUC)

  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).

  28 days

• Part 4 - Maximum concentration (Cmax) of omaveloxolone

  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine maximum observed concentration (Cmax).

  23 days

• Part 4 - Area under the omaveloxolone concentration-time curve (AUC)

  Pharmacokinetics will be assessed by blood sampling for omaveloxolone to determine area under the curve (AUC).

  28 days

Study Arms (4)

Omaveloxolone and Multiple Drugs (Part 1)

EXPERIMENTAL

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

Drug: Omaveloxolone; Drug: Midazolam oral solution; Drug: Repaglinide 1 MG; Drug: MetFORMIN 500 Mg Oral Tablet; Drug: Rosuvastatin; Drug: Digoxin tablet

Omaveloxolone & Gemfibrozil (Part 2)

EXPERIMENTAL

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

Drug: Omaveloxolone; Drug: Gemfibrozil Tablets

Omaveloxolone and Itraconazole (Part 3)

EXPERIMENTAL

Single oral doses of 150 mg omaveloxolone on Days 1 and 13. Oral doses of 200 mg itraconazole on Days 10 to 18.

Drug: Omaveloxolone; Drug: Itraconazole capsule

Omaveloxolone and Verapamil (Part 4)

EXPERIMENTAL

Single oral doses of 150 mg omaveloxolone on Days 1 and 13. Oral doses of 120 mg verapamil on Days 10 to 18.

Drug: Omaveloxolone; Drug: Verapamil Pill

Interventions

Omaveloxolone DRUG

50 mg capsules

Also known as: RTA 408

Omaveloxolone & Gemfibrozil (Part 2); Omaveloxolone and Itraconazole (Part 3); Omaveloxolone and Multiple Drugs (Part 1); Omaveloxolone and Verapamil (Part 4)

Midazolam oral solution DRUG

2 mg/mL oral solution

Omaveloxolone and Multiple Drugs (Part 1)

Repaglinide 1 MG DRUG

1 mg tablet

Omaveloxolone and Multiple Drugs (Part 1)

MetFORMIN 500 Mg Oral Tablet DRUG

500 mg tablet

Omaveloxolone and Multiple Drugs (Part 1)

Rosuvastatin DRUG

10 mg tablet

Omaveloxolone and Multiple Drugs (Part 1)

Digoxin tablet DRUG

0.25 mg tablet

Omaveloxolone and Multiple Drugs (Part 1)

Gemfibrozil Tablets DRUG

600 mg tablet

Omaveloxolone & Gemfibrozil (Part 2)

Itraconazole capsule DRUG

100 mg capsule

Omaveloxolone and Itraconazole (Part 3)

Verapamil Pill DRUG

120 mg tablet

Omaveloxolone and Verapamil (Part 4)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead
• Covance: collaborator

Study Sites (1)

Covance Clinical Research Unit (CRU) Inc.

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

omaveloxolone; Midazolam; repaglinide; Metformin; Tablets; Rosuvastatin Calcium; Digoxin; Gemfibrozil; Itraconazole; Verapamil

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Pentanoic Acids; Valerates; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Fatty Acids, Volatile; Fatty Acids; Lipids; Triazoles; Azoles; Piperazines; Phenethylamines; Ethylamines; Amines

Study Officials

• Jennifer Zon, MD

  Covance CRU Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 5, 2019
• Study Start: June 14, 2019
• Primary Completion: August 18, 2019
• Study Completion: August 28, 2019
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)