A Pharmacokinetic Study of Omaveloxolone in Subjects With Hepatic Impairment and Normal Hepatic Function

NCT03902002 | Completed Phase 1 FDA Drug

• 1 other identifier: 408-C-1804
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

This study will examine the pharmacokinetics (PK) of omaveloxolone following a single oral dose of omaveloxolone in subjects with mild, moderate, or severe hepatic impairment compared to healthy subjects with normal hepatic function.

Conditions

Hepatic Impairment

Keywords

RTA 408; RTA 408 capsules; Omaveloxolone; Omaveloxolone capsules; Hepatic impairment

Outcome Measures

Primary Outcomes (2)

• Maximum concentration (Cmax) of omaveloxolone in plasma

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

  15 days

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

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

  15 days

Secondary Outcomes (1)

• Count of reported adverse events

  15 days

Study Arms (4)

Group 1: matched healthy subjects

EXPERIMENTAL

On the morning of Day 1, following an overnight fast of at least 10 hours, a single oral dose of 150 mg omaveloxolone (3 × 50 mg capsules) will be administered with 240 mL of water. No food will be allowed for 4 hours post dose. Pharmacokinetic samples will be obtained from pre dose until 336 hours post dose.

Drug: Omaveloxolone 50 mg capsules

Group 2: subjects with mild hepatic impairment

EXPERIMENTAL

On the morning of Day 1, following an overnight fast of at least 10 hours, a single oral dose of 150 mg omaveloxolone (3 × 50 mg capsules) will be administered with 240 mL of water. No food will be allowed for 4 hours post dose. Pharmacokinetic samples will be obtained from pre dose until 336 hours post dose.

Drug: Omaveloxolone 50 mg capsules

Group 3: subjects with moderate hepatic impairment

EXPERIMENTAL

On the morning of Day 1, following an overnight fast of at least 10 hours, a single oral dose of 150 mg omaveloxolone (3 × 50 mg capsules) will be administered with 240 mL of water. No food will be allowed for 4 hours post dose. Pharmacokinetic samples will be obtained from pre dose until 336 hours post dose.

Drug: Omaveloxolone 50 mg capsules

Group 4: subjects with severe hepatic impairment

EXPERIMENTAL

On the morning of Day 1, following an overnight fast of at least 10 hours, a single oral dose of 150 mg omaveloxolone (3 × 50 mg capsules) will be administered with 240 mL of water. No food will be allowed for 4 hours post dose. Pharmacokinetic samples will be obtained from pre dose until 336 hours post dose.

Drug: Omaveloxolone 50 mg capsules

Interventions

Omaveloxolone 50 mg capsules DRUG

Capsules containing 50 mg of omaveloxolone

Also known as: RTA 408

Group 1: matched healthy subjects; Group 2: subjects with mild hepatic impairment; Group 3: subjects with moderate hepatic impairment; Group 4: subjects with severe hepatic impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, of any race, between 18 and 70 years of age, inclusive.
• BMI between 18.0 and 38.0 kg/m2, inclusive, and body weight ≥ 50 kg.
• Females will not be pregnant (or planning to get pregnant) or lactating at Screening or Check in (Day 1), and females of childbearing potential and males will agree to use contraception .
• Male subjects must not donate sperm and female subjects must not donate ova from Check in (Day 1) until 90 days after their dose of study drug.
• Subjects with Normal Hepatic Function Only
• Matched to subjects with mild, moderate, or severe hepatic impairment in sex, age (± 10 years), and BMI (± 20%).
• In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital non hemolytic hyperbilirubinemia \[e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at Screening and Check in as assessed by the investigator (or designee).
• Subjects with Hepatic Impairment Only
• Documented chronic stable liver disease (Child Pugh Class A \[mild\], B \[moderate\], or C \[severe\] at Screening); diagnosis of cirrhosis due to parenchymal liver disease. This will exclude biliary liver cirrhosis or other causes of hepatic impairment not related to parenchymal disorder:
• 'Documented' is defined by at least one of the following: medical history, physical examination, hepatic ultrasound, computed axial tomography scan, magnetic resonance imaging, and/or liver biopsy.
• 'Chronic stable' is defined as no clinically significant change in disease status within the last 30 days, as documented by the subject's recent medical history (e.g., no worsening of clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin time \[PT\] by more than 50%).
• Subjects with mild, moderate, or severe hepatic impairment may have medical findings consistent with their hepatic dysfunction, as determined by medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations at Screening and Check in (Day 1). Subjects with abnormal findings considered not clinically significant by the investigator will be eligible.

You may not qualify if:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric 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).
• Presence of any other condition (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines.
• Ventricular dysfunction or history of risk factors for Torsade de Pointes (TdP; e.g., unexplained syncope, known long QT syndrome, heart failure, and cardiomyopathy). Subjects will be excluded if there is a family history of long QT syndrome.
• Evidence of hepatorenal syndrome and estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 or abnormal sodium and potassium levels, as determined by the investigator (or designee), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation at Screening or Check in (Day 1).
• Clinically significant physical examination abnormality, as determined by the investigator (or designee).
• 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).
• Use of any sensitive substrates for cytochrome P450 (CYP)2C8, moderate or strong inhibitors or inducers of CYP3A4/5, or substrates for p glycoprotein (P gp) within 30 days prior to study drug administration.
• Consumption of grapefruit, grapefruit products, star fruit, star fruit products, or Seville oranges within 72 hours prior to study drug administration (Day 1) and throughout the study (until after the Follow up Visit).
• History of alcoholism or drug/chemical abuse within 6 months prior to Check in (Day 1).
• Alcohol consumption of \> 21 units per week for males and \> 14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine within the 6 months prior to Check in (Day 1).
• Positive urine drug screen or positive alcohol breath or urine test result at Screening and Check in (Day 1), that is not otherwise explained by permitted concomitant medications. A positive alcohol test may be repeated once at Screening. A positive alcohol test may not be repeated at Check in (Day 1).
• Positive human immunodeficiency virus test (Appendix 2).
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 10 half lives (if known), whichever is longer, prior to dosing.

Sponsors & Collaborators

• Biogen: lead

Study Sites (3)

Orange County Research Center

Tustin, California, 92780, United States

Location

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

omaveloxolone

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: March 26, 2019
• First Posted: April 3, 2019
• Study Start: July 19, 2019
• Primary Completion: January 27, 2020
• Study Completion: January 27, 2020
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (3)