Single-Dose, Open-Label Pharmacokinetic Study of Bardoxolone Methyl in Subjects With Mild, Moderate, and Severe Hepatic Impairment and Normal Hepatic Function

NCT01563562 | Completed Phase 1

• 1 other identifier: 402-C-1002
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the pharmacokinetic profile of bardoxolone methyl following a single oral dose of 20 mg bardoxolone methyl in subjects with mild, moderate, and severe hepatic impairment, as compared to healthy volunteers.

Conditions

Hepatic Impairment; Healthy

Outcome Measures

Primary Outcomes (1)

• Area under the plasma concentration-time curve

  0, 0.5,1, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 264, 312, and 360 hours following dose administration

Secondary Outcomes (4)

• Time to maximum observed concentration

  0, 0.5,1, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 264, 312, and 360 hours following dose administration

• Oral clearance

  0, 0.5,1, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 264, 312, and 360 hours following dose administration

• Terminal half-life

  0, 0.5,1, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 264, 312, and 360 hours following dose administration

• Terminal rate constant

  0, 0.5,1, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 264, 312, and 360 hours following dose administration

Study Arms (1)

Bardoxolone Methyl 20 mg

EXPERIMENTAL

Drug: Bardoxolone Methyl

Interventions

Bardoxolone Methyl DRUG

Oral, Single dose

Bardoxolone Methyl 20 mg

Eligibility Criteria

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

You may qualify if:

• All subjects
• Male or female subjects between 18 and 70 years, inclusive; must meet all of the following criteria to be included in the study:
• Willing to practice method of birth control (both males who have partners of childbearing potential and females of childbearing potential) during screening, while taking study drug and for at least 30 days after the last dose of study drug is ingested;
• Female subjects of childbearing potential must be non-pregnant and non-lactating and have a negative serum pregnancy test result before enrollment into the study;
• Body mass index (BMI) between 18 and 37 kg/m2;
• Willing and able to give written informed consent for study participation;
• Willing and able to cooperate with all aspects of the protocol.
• Subjects with hepatic impairment
• Have documented evidence of hepatic cirrhosis by biopsy, nuclear scan, CT, MRI, ultrasound, or other clinically acceptable methods; must meet all of the following criteria to be included in the study:
• Be classified as Child-Pugh class A (mild), B (moderate), or C (severe). (See Appendix A for Child-Pugh system.)

You may not qualify if:

• All subjects
• Participated in another clinical trial of an investigational drug (or a medical device) within 30 days of Study Day -1, or are currently participating in another trial of an investigational drug (or a medical device); with any of the following conditions or characteristics must be excluded from the study:
• Known hypersensitivity to any component in the formulation of the study drug, bardoxolone methyl;
• Any medical or dental procedure, no matter how minor, that is planned or anticipated to occur during the conduct of the study;
• History of drug or alcohol abuse or dependence within the last year;
• Donation or receipt of blood or blood components within the 4 weeks prior to Study Day -1. The investigator should instruct subjects who participate in this study not to donate blood or blood components for 4 weeks after the completion of the study;
• Abnormal screening ECG which is interpreted by the investigator to be clinically significant;
• A positive test for drug(s) of abuse (ethanol, amphetamines, benzodiazepines, barbiturates, cocaine, opiates, or cannabinoids) at the screening or the Day -1 visit, unless the positive drug screen is for a subject with hepatic impairment for a prescription drug and is approved by the principal investigator;
• Female subjects who are planning a pregnancy or are pregnant or lactating;
• Deemed by the investigator to be inappropriate for this study, including subjects who are unable to communicate with the investigator due to language problems, poor mental development, or impaired cerebral function;
• Any concurrent clinical conditions that in the judgment of the investigator could either potentially pose a health risk to the subject while involved in the study or could potentially influence the study outcome;
• Positive test results for human immunodeficiency virus type 1 or 2 antibody at screening;
• Have an estimated creatinine clearance \< 60 mL/min on Study Day -1 using the Cockcroft-Gault equation (Appendix B);
• Any condition possibly affecting absorption, distribution, metabolism or excretion of drugs that may confound the analyses conducted in this study (for example: previous surgery on the gastrointestinal tract that includes removal of parts of stomach, bowel, liver, gall bladder, pancreas, venacaval shunts, or transjugular intrahepatic portosystemic shunts\]).
• Subjects with hepatic impairment

Sponsors & Collaborators

• Biogen: lead

Study Sites (2)

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

bardoxolone methyl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2012
• First Posted: March 27, 2012
• Study Start: April 30, 2012
• Primary Completion: November 30, 2012
• Study Completion: November 30, 2012
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (2)