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Effect of Itraconazole on the Pharmacokinetics of Bardoxolone Methyl in Healthy Adults

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ClinicalTrials.gov Identifier: NCT03264079
Recruitment Status : Completed
First Posted : August 28, 2017
Last Update Posted : November 29, 2017
Sponsor:
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

Brief Summary:

This trial will study the impact of a strong CYP3A4 inhibitor (itraconazole) on the pharmacokinetics of bardoxolone methyl (RTA 402) in healthy adult subjects.

This is an open-label, fixed-sequence crossover pharmacokinetic (PK) study in healthy volunteers.

Subjects will complete a screening visit within 28 days of Study Day 1. Subjects must qualify for the study based on inclusion/exclusion criteria. For Period 1, all qualified subjects shall receive a single oral dose of bardoxolone methyl (10 mg) on Day 1. For Period 2, following a washout of 14 days, itraconazole (SPORANOX®) capsules (100 mg) will be administered as a 200-mg single daily dose on Study Days 15 through 27, with bardoxolone methyl (10 mg) administered on Day 18 (1 hour after itraconazole administration).

Bardoxolone methyl doses will be administered under fasted conditions. Itraconazole will be administered under fed conditions on Study Days 15-17, and Study Days 19-27.

On study Day 18, itraconazole will be administered under fasted conditions. Subjects will be confined beginning on Study Day -1 through the last blood sample collection on Study Day 9 during Period 1, and from Study Day 14 through the last PK blood draw on Study Day 28 during Period 2.


Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Bardoxolone methyl capsules 10 mg Drug: Itraconazole capsules 100 mg Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Intervention Model Description:

All participants are placed into a one group to receive two interventions: one intervention during Period 1 and a second intervention during Period 2.

For Period 1, all qualified subjects shall receive a single oral dose of bardoxolone methyl (10 mg) on Day 1.

For Period 2, following a washout of 14 days, itraconazole (SPORANOX®) capsules (100 mg) will be administered as a 200-mg single daily dose on Study Days 15 through 27, with bardoxolone methyl (10 mg) administered on Day 18 (1 hour after itraconazole administration)

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study of the Effect of a Strong CYP3A4 Inhibitor (Itraconazole) on the Pharmacokinetics of Bardoxolone Methyl in Healthy Volunteers
Actual Study Start Date : October 16, 2017
Actual Primary Completion Date : November 13, 2017
Actual Study Completion Date : November 13, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Bardoxolone methyl 10 mg and Itraconazole 200 mg
Period 1: Bardoxolone methyl capsules 10 mg Period 2: two Itraconazole capsules 100 mg
Drug: Bardoxolone methyl capsules 10 mg
One 10 mg capsule of bardoxolone methyl administered on Study Day 1 (Period 1) of the trial and one 10 mg capsule of bardoxolone methyl administered on Study Day 18 (Period 2) of the trial
Other Name: RTA 402

Drug: Itraconazole capsules 100 mg
Two 100 mg capsules of itraconazole administered once daily during Study Days 15 - 27 (Period 2) of the trial
Other Name: Sporanox




Primary Outcome Measures :
  1. Area under the plasma concentration-time curve of bardoxolone methyl from time 0 to the last measurable time point (AUC0-t). [ Time Frame: 28 days ]
  2. Area under the plasma concentration-time curve of bardoxolone methyl extrapolated to infinity (AUC0-inf) [ Time Frame: 28 days ]
  3. Maximum observed drug concentration (Cmax) in plasma of bardoxolone methyl [ Time Frame: 28 days ]


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

Inclusion Criteria:

  • Male or female and age is between 18 and 55 years, inclusive;
  • Female subjects of childbearing potential must not be planning a pregnancy, pregnant, or lactating, and must have a negative serum pregnancy test result before enrollment into the study, and must be willing to use contraception as specified or abstain from sexual activity for the duration of the study;
  • If male, subject must be surgically sterile or practicing an approved method of contraception, from initial study drug administration through 90 days after administration of the last dose of study drug;
  • If male, subject agrees to abstain from sperm donation through 90 days after administration of the last dose of study drug;
  • Body Mass Index (BMI) is ≥ 18 to ≤31 kg/m2, inclusive;
  • A condition of general good health, based upon the results of a medical history, physical examination, vital signs, laboratory profile, and a 12-lead electrocardiogram (ECG), as judged by the investigator;
  • Must voluntarily sign and date each informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

  • History of clinically significant drug allergies, including allergies to any of the components of the investigational product and/or clinically significant food allergies as determined by the investigator;
  • 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;
  • Known hypersensitivity to any component in the formulations of bardoxolone methyl, or SPORANOX®;
  • 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 30-day period prior to study drug administration or within 5 half-lives (if known), whichever is longer;
  • Recent (6-month) history of drug or alcohol abuse;
  • B-type natriuretic peptide (BNP) level >200 pg/mL at screening;
  • Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or HIV antibodies (HIV Ab) at screening;
  • Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt of a transfusion of any blood product within 8 weeks prior to study drug administration;
  • 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 prior to study drug administration;
  • Positive screen results for drugs of abuse, alcohol, or cotinine at screening or Day -1;
  • Consumption of alcohol within 72 hours prior to study drug administration;
  • Consumption of grapefruit, grapefruit products, star fruit, star fruit products, or Seville oranges within the 72-hour period prior to 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;
  • Screening laboratory analyses that show any of the following abnormal laboratory results:

    1. Alanine transaminase (ALT) or aspartate aminotransferase (AST) levels above the upper limit of normal (ULN);
    2. Clinically significant abnormal ECG; ECG with QTc using Fridericia's correction formula (QTcF) > 450 msec is exclusionary;
    3. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive either bardoxolone methyl or itraconazole.

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): NCT03264079


Locations
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United States, Ohio
Medpace Clinical Pharmacology Unit
Cincinnati, Ohio, United States, 45227
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.

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Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03264079     History of Changes
Other Study ID Numbers: 402-C-1701
First Posted: August 28, 2017    Key Record Dates
Last Update Posted: November 29, 2017
Last Verified: November 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Reata Pharmaceuticals, Inc.:
RTA 402
Bardoxolone methyl
Itraconazole
Sporanox
CYP3A4
Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors