An Open-Label Study of the Effect of Bardoxolone Methyl on the Single Dose Pharmacokinetics of Digoxin and Rosuvastatin in Healthy Volunteers

NCT01598363 | Completed Phase 1

• 1 other identifier: 402-C-1104
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the potential effect of bardoxolone methyl on the pharmacokinetics of digoxin and rosuvastatin and to assess the safety of the concomitant administration of bardoxolone methyl with digoxin or rosuvastatin.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Maximum observed concentration

  For Digoxin and Rosuvastatin

  0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Secondary Outcomes (10)

• Time to maximum observed concentration

  0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

• Area under the plasma-concentration time-curve

  0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

• Oral clearance

  0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

• Terminal rate constant

  0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

• Terminal half-life

  0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Study Arms (2)

Digoxin 0.5mg, Bardoxolone Methyl 20mg and 60mg

EXPERIMENTAL

Drug: Digoxin

Rosuvastatin 20mg, Bardoxolone Methyl 20mg and 60mg

EXPERIMENTAL

Drug: Rosuvastatin

Interventions

Digoxin DRUG

Oral, Day 1 and Day 10

Digoxin 0.5mg, Bardoxolone Methyl 20mg and 60mg

Rosuvastatin DRUG

Oral, Day 1 and Day 10

Rosuvastatin 20mg, Bardoxolone Methyl 20mg and 60mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects between 18 and 45 years, inclusive;
• Willing to practice a 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;
• Body mass index (BMI) between 19 and 31 kg/m2, inclusive;
• Willing and able to give written informed consent for study participation;
• Willing and able to cooperate with all aspects of the protocol.

You may not qualify if:

• Participated in another clinical trial of an investigational drug (or medical device) within 30 days before Study Day -1, or are currently participating in another trial of an investigational drug (or medical device);
• 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);
• Known hypersensitivity to any component in the formulation of bardoxolone methyl, LANOXIN®, or CRESTOR®;
• Evidence or history of or concurrent clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of dose administration), hematological, endocrine, immunological, renal, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease that in the judgment of the investigator could potentially either pose a health risk to the subject during the study or influence the study outcome;
• Evidence of hepatic or biliary dysfunction including elevation of total bilirubin, direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), or alkaline phosphatase levels to greater than the upper limit of normal (ULN);
• Positive test results for human immunodeficiency virus type 1 or 2 antibody, hepatitis B surface antigen, or hepatitis C virus antibody at screening;
• Any medical or dental procedure, no matter how minor, that is planned or anticipated to occur during the conduct of the study;
• History of alcohol abuse or dependence within the last year;
• Any vaccination within 30 days before start of this study and throughout the study;
• Use of aspirin, non-steroidal anti-inflammatory agents, or acetaminophen within 5 days before Study Day 1; use of aspirin or non-steroidal anti-inflammatory agents (but not acetaminophen) will be allowed for isolated episodes of pain at the discretion of the investigator;
• Use of or need for any systemic drug(s) including vitamins or herbal preparations other than drugs used for contraception, within 30 days before entry into the study or during the study;
• Donation or receipt of blood or blood components within the 4 weeks before 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;
• Any diagnostic or intervention procedure requiring a contrast agent within the 30 days before study participation;
• Systolic blood pressure \> 140mmHg or \< 100mmHg or a diastolic blood pressure \>95 mmHg at screening measured after 5 minutes in a sitting position;
• A pulse rate at rest in a sitting position of \< 50 bpm or \> 100 bpm;

Sponsors & Collaborators

• Biogen: lead

Study Sites (1)

Spaulding Clinical Research, LLC

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Interventions

Digoxin; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: May 11, 2012
• First Posted: May 15, 2012
• Study Start: June 30, 2012
• Primary Completion: July 31, 2012
• Study Completion: July 31, 2012
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)