A TQTc Study for Omaveloxolone

• ClinicalTrials.gov Identifier: NCT05927649
• Recruitment Status: Completed
• First Posted: July 3, 2023
• Last Update Posted: February 2, 2024
• Sponsor: Reata, a wholly owned subsidiary of Biogen
• Collaborators: Celerion; Q2 Solutions
• Information provided by (Responsible Party): Biogen ( Reata, a wholly owned subsidiary of Biogen )

Study Description

Brief Summary:

This is a randomized, double blind, placebo and active (moxifloxacin open label) controlled study in healthy subjects to assess the effect of the supratherapeutic exposure of omaveloxolone on QTc interval. Moxifloxacin will be used as an active control and will be administered as open label. Omaveloxolone and placebo will be administered in a blinded fashion. All treatments will be administered after an FDA high-fat meal. Concentration-QTc (C-QTc) analysis is the primary analysis for the study.

Condition or disease	Intervention/treatment	Phase
Health Adult Subjects	Drug: Omaveloxolone; Drug: Moxifloxacin	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Double-Blind, Placebo- and Active-Controlled, 3-Way Crossover Study in Healthy Subjects to Determine the Effect of Omaveloxolone on QTc Interval
• Actual Study Start Date: July 11, 2023
• Actual Primary Completion Date: September 1, 2023
• Actual Study Completion Date: September 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sequence ABC; Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment A (Period 1 from Day 1 - 15), Treatment B (Period 2 from Day 15 - 29), and Treatment C(Period 3 from Day 29 -32)	Drug: Omaveloxolone; Omaveloxolone capsules; Other Name: RTA 408; Drug: Moxifloxacin; Moxifloxacin capsules
Experimental: Sequence BAC; Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment B (Period 1 from Day 1-15), Treatment A (Period 2 from Day 15 - 29, and Treatment C (Period 3 from Day 29 to 32)	Drug: Omaveloxolone; Omaveloxolone capsules; Other Name: RTA 408; Drug: Moxifloxacin; Moxifloxacin capsules
Experimental: Sequence ACB; Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo 450 mg and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment A (Period 1 from Day 1-15), Treatment C (Period 2 from Day 15 -18), and Treatment B (Period 3from Day 18 - 32)	Drug: Omaveloxolone; Omaveloxolone capsules; Other Name: RTA 408; Drug: Moxifloxacin; Moxifloxacin capsules
Experimental: Sequence BCA; Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment B (Period 1 from Day 1 - 15), Treatment C (Period 2 from Day 15 to 18), and Treatment A (Period 3 from Day 18 - 32)	Drug: Omaveloxolone; Omaveloxolone capsules; Other Name: RTA 408; Drug: Moxifloxacin; Moxifloxacin capsules
Experimental: Sequence CAB; Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment C (Period 1 from Day 1 - 4), Treatment A (Period 2 from Day 4 - 18), and Treatment B (Period 3 from Day 18 - 32)	Drug: Omaveloxolone; Omaveloxolone capsules; Other Name: RTA 408; Drug: Moxifloxacin; Moxifloxacin capsules
Experimental: Sequence CBA; Subjects receive three treatments (A: omaveloxolone 450 mg, B: omaveloxolone matching placebo and C: moxifloxacin 400 mg) administered in a single dose with the standard FDA high-fat meal in three periods. Treatment C (Period 1 from Day 1 - 4), Treatment B (Period 2 from Day 4 - 18), and Treatment A (Period 3 from Day 18 - 32)	Drug: Omaveloxolone; Omaveloxolone capsules; Other Name: RTA 408; Drug: Moxifloxacin; Moxifloxacin capsules

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in placebo-corrected QTcF (∆∆QTcF) [ Time Frame: At Day 1 of each period, which is 14 days for both Treatment A and Treatment B and 4 days for Treatment C ]
   The relationship between ∆QTcF and omaveloxolone and its metabolites, M17 and M22 plasma concentrations will be investigated by a linear mixed effects modeling approach with ∆ QTcF as the dependent variable, time-matched concentration of omaveloxolone and its metabolites as a continuous covariate (ie, 0 for placebo), and centered baseline QTcF as an additional covariate, treatment (active = 1; or placebo = 0) and time as categorical factors, and a random intercept and slope per subject.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy adult males and/or females, 18 to 55 years of age (inclusive) at the time of screening.
• BMI at screening between 18.0 and 32.0 kg/m2 (inclusive)
• 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:

• History of clinically significant drug allergies, including allergies to any of the components of the study drugs (omaveloxolone and moxifloxacin) and/or clinically significant food allergies as determined by the investigator.
• Subject has an ECG abnormality, including corrected QT interval (QTc)> 450 msec for males, and > 460 msec for females, HR < 45 bpm or > 100 bpm after 5 minutes in supine position, PR interval > 220 msec, or QRS interval > 110 msec.
• Subject has allergy to band aids, adhesive dressing, or medical tape.
• Subject has hypotension (systolic blood pressure blood pressure [BP] ≤ 90 mmHg, diastolic BP ≤ 50 mmHg), or hypertension (systolic BP ≥ 140 mmHg, diastolic BP ≥ 90 mmHg) at screening.
• Subject has history of prolonged QTc, cardiac arrhythmia, or first-degree relatives with congenital Long QT syndrome or unexplained sudden death in young age.
• Subject has a history of unstable angina, syncope, coronary artery disease, myocardial infarction, congestive heart failure (CHF), transient ischemic attack (TIA), or neurological disorder.
• Presence or history of any significant cardiovascular, gastrointestinal, hepatic, renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease, as determined by the investigator.
• Presence of any other condition (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines.
• Requirement for any over the counter and/or prescription medication, vitamins, and/or herbal supplements on a regular basis
• Use of any medications (over the counter and/or prescription medication), vitamins, and/or herbal supplements, within the 14-days prior to study drug administration or within 5 halflives (if known), whichever is longer
• History of drug or alcohol abuse in the last 6 months as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition.
• Positive test result for drugs of abuse, alcohol, or cotinine at screening or Day -1.
• Positive test result for hepatitis B surface antigen, hepatitis C virus antibodies, or HIV antibodies at screening.
• Positive test result for COVID-19 at Day -1.
• Blood donation (excluding plasma donation) of approximately 500 mL within 56 days before screening or plasma donation within 7 days before screening.
• Receipt of any investigational product within a time period equal to 10 half-lives of the product, if known, or a minimum of 30 days before study drug administration.
• Consumption of alcohol within 72 hours before study drug administration.
• Consumption of grapefruit, grapefruit products, star fruit, star fruit products, Seville oranges, or Seville orange products within the 72-hour period before study drug administration.
• Use of tobacco or nicotine-containing products within the 6-month period preceding study drug administration.
• Current enrollment in another clinical study.
• Previous enrollment in any clinical study involving omaveloxolone.

Contacts and Locations

Locations

United States, Arizona

Celerion, Inc.

Tempe, Arizona, United States, 85283

Sponsors and Collaborators

Reata, a wholly owned subsidiary of Biogen

Celerion

Q2 Solutions

Investigators

• Principal Investigator: Michelle Valentine, DO; Celerion

More Information

• Responsible Party: Reata, a wholly owned subsidiary of Biogen
• ClinicalTrials.gov Identifier: NCT05927649
• Other Study ID Numbers: 408-C-2201
• First Posted: July 3, 2023
• Last Update Posted: February 2, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Biogen ( Reata, a wholly owned subsidiary of Biogen ):

C-QTc; omaveloxolone; TWTc; moxifloxacin

Additional relevant MeSH terms:

Moxifloxacin; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents