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Trial record 31 of 31 for:    Bardoxolone methyl OR CDDO-Me OR RTA 402

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

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ClinicalTrials.gov Identifier: NCT01598363
Recruitment Status : Completed
First Posted : May 15, 2012
Last Update Posted : November 2, 2012
Sponsor:
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Digoxin Drug: Rosuvastatin Phase 1

Detailed Description:
Subjects in Cohort 1 will receive a single dose of digoxin (0.5 mg) on Study Day 1, an initial dose of bardoxolone methyl (60 mg) and a single dose of digoxin (0.5 mg) on Study Day 10, and once daily doses of bardoxolone methyl (20 mg) on Study Days 11 through 14. Subjects in Cohort 2 will receive a single dose of rosuvastatin (20 mg) on Study Day 1, an initial dose of bardoxolone methyl (60 mg) and a single dose of rosuvastatin (20 mg) on Study Day 10, and once daily doses of bardoxolone methyl (20 mg) on Study Days 11 through 14. All doses will be given in the morning under fasting conditions. Bardoxolone methyl and the probe substrates (digoxin, rosuvastatin) will be dosed at the same time. Confinement will begin on Study Day -1 (Study Day before the first dosing day) and end after the collection of the 216 hour blood samples and scheduled study procedures on Study Day 19.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Study Start Date : June 2012
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

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Arm Intervention/treatment
Experimental: Digoxin 0.5mg, Bardoxolone Methyl 20mg and 60mg Drug: Digoxin
Oral, Day 1 and Day 10

Experimental: Rosuvastatin 20mg, Bardoxolone Methyl 20mg and 60mg Drug: Rosuvastatin
Oral, Day 1 and Day 10




Primary Outcome Measures :
  1. Maximum observed concentration [ Time Frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose ]
    For Digoxin and Rosuvastatin


Secondary Outcome Measures :
  1. Time to maximum observed concentration [ Time Frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose ]
    For Digoxin and Rosuvastatin

  2. Area under the plasma-concentration time-curve [ Time Frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose ]
    For Digoxin and Rosuvastatin

  3. Oral clearance [ Time Frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose ]
    For Digoxin and Rosuvastatin

  4. Terminal rate constant [ Time Frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose ]
    For Digoxin and Rosuvastatin

  5. Terminal half-life [ Time Frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose ]
    For Digoxin and Rosuvastatin

  6. Amount excreted in Urine [ Time Frame: 0-24, 24-48, 484-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216 hours post-dose ]
    For Digoxin only

  7. Fraction of the dose excreted in Urine [ Time Frame: 0-24, 24-48, 484-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216 hours post-dose ]
    For Digoxin only

  8. Renal clearance [ Time Frame: 0-24, 24-48, 484-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216 hours post-dose ]
    For Digoxin only

  9. Number of patients with Adverse Events [ Time Frame: Approximately 1 year ]
  10. Determination of concentration for Bardoxolone Methyl [ Time Frame: 0 hours and 3 hours after dosing ]
    Sample will be taken at 0 hours and 3 hours after dosing only on Study Days 10, 12 and 14



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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;
  • Abnormal screening ECG (including a QTcF interval of >450 ms) which is interpreted by the investigator to be clinically significant, or any clinical evidence of Wolff-Parkinson-White syndrome, intermittent complete heart block, second degree heart block or prolonged PR interval of ≥ 200 msec on the 12-lead ECG;
  • Use of tobacco- or nicotine-containing products (that is, cigarettes, cigars, chewing tobacco, snuff, etc) or products for smoking cessation within 2 weeks before Study Day -1;
  • Consumed alcohol or xanthine-containing products (e.g., tea, coffee, chocolate, cola, etc.) within 72 hours before Study Day -1;
  • Treated with any investigational agent within 30 days before Study Day -1, 5 half-lives or twice the duration of biological effect of the previous investigational drug (whichever is longer);
  • A history of drug abuse or who test positive for drug(s) of abuse (ethanol, amphetamines, benzodiazepines, barbiturates, cocaine, opiates, or cannabinoids) or cotinine (indicating active current smoking) at the screening or Study Day -1;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01598363


Locations
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United States, Wisconsin
Spaulding Clinical Research, LLC
West Bend, Wisconsin, United States, 53095
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.

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Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01598363     History of Changes
Other Study ID Numbers: 402-C-1104
First Posted: May 15, 2012    Key Record Dates
Last Update Posted: November 2, 2012
Last Verified: November 2012

Additional relevant MeSH terms:
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Rosuvastatin Calcium
Digoxin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Anti-Arrhythmia Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs