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

A Phase 1, Open-Label, 4-Part, Drug-Drug Interaction Study With Omaveloxolone in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Omaveloxolone; Drug: Midazolam oral solution; Drug: Repaglinide 1 MG; Drug: MetFORMIN 500 Mg Oral Tablet; Drug: Digoxin tablet; Drug: Gemfibrozil Tablets; Drug: Itraconazole capsule; Drug: Verapamil Pill

Detailed Description

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Clinical Research Unit (CRU) Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Rosuvastatin; 10 mg tablet; Drug: Omaveloxolone; 50 mg capsules; Other Names: 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: Digoxin tablet; 0.25 mg 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	Drug: Omaveloxolone; 50 mg capsules; Other Names: RTA 408; Drug: Gemfibrozil Tablets; 600 mg tablet
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.	Drug: Omaveloxolone; 50 mg capsules; Other Names: RTA 408; Drug: Itraconazole capsule; 100 mg 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.	Drug: Omaveloxolone; 50 mg capsules; Other Names: RTA 408; Drug: Verapamil Pill; 120 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Reata, a wholly owned subsidiary of Biogen
• Collaborators: Covance
• Investigators: Principal Investigator: Jennifer Zon, MD, Covance CRU Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2019
• Primary Completion (Actual): August 18, 2019
• Study Completion (Actual): August 28, 2019

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 2, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: RTA 408; omaveloxolone; DDI; RTA 408 capsules; omaveloxolone capsules
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Anti-Infective Agents; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antimetabolites; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Antifungal Agents; Steroid Synthesis Inhibitors; Calcium Channel Blockers; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C8 Inhibitors; Digoxin; Midazolam; Rosuvastatin Calcium; Metformin; Itraconazole; Verapamil; Gemfibrozil; Repaglinide
• Other Study ID Numbers: 408-C-1806

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No