Impact of Rifabutin on the Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor

August 8, 2024 updated by: Paul Beringer, University of Southern California
This is a prospective, single-center, fixed-sequence, nonrandomized, open-label study in healthy adults to investigate the impact of rifabutin on the pharmacokinetics of trikafta.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Trikafta (Elexacaftor [ELX], Tezacaftor [TEZ], Ivacaftor[IVA]) is contraindicated with concomitant use of strong inducers as co-administration of rifampin decreased the area-under-the concentration time curve (AUC) of IVA by 89%, creating a therapeutic challenge to the treatment of non-tuberculosis mycobacteria (NTM) infection in people with cystic fibrosis (CF). While rifabutin also induces CYP3A4 activity, its effects appear to be more moderate when compared with rifampin. Therefore, we hypothesize that rifabutin can be co-administered with an adjusted dose of ELX/TEZ/IVA in patients being treated for NTM pulmonary disease.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Paul M. Beringer, PharmD
  • Phone Number: 323-442-1402
  • Email: beringer@usc.edu

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Able and willing to sign informed consent prior to any study-related activities.
  • Male or female participants between 18 and 65 years of age inclusive.
  • Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination findings, and clinical laboratory test results
  • Body mass index (BMI) of 17.5 to 30.5 kg/m2, inclusive; and a total body weight >50kg (110 lbs).
  • Willing to stop using any herbal or natural health products for 2 weeks prior to and during the study including: Grapefruit, grapefruit juice, St. John's Wort.
  • Participant must use a reliable method of birth control while they are participating in the study; for instance an intrauterine device (IUD), condom with spermicidal gel or foam, diaphragm with spermicidal gel or foam, vasectomy, tubal ligation, hysterectomy or abstinence or female must be post-menopausal for at least one year.

Exclusion Criteria:

  • Female subjects of childbearing potential with positive urine pregnancy test at screening.
  • Female subjects who are breastfeeding.
  • Use of CYP3A modulators (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin, azole drugs, telithromycin, clarithromycin, erythromycin)
  • Any significant acute or chronic medical illness that might confound the results of the study or pose an additional risk in administrating study drugs to the subject, as determined by the investigator.
  • Any condition that could affect drug absorption (eg, gastrectomy, pancreatitis).
  • Any major surgery within 4 weeks of study drug administration.
  • Blood donation of approximately 1 pint (500 mL) within 56 days before study drug administration.
  • Known hypersensitivity to rifamycins
  • Patients with hepatic impairment (Child-Pugh Class B or C) and/or with history of hepatobiliary disease or liver function test elevations.
  • Renal insufficiency (eGFR < 60 mL/min)
  • History of uveitis and/or current eye or vision problems with the exception of corrective lenses.
  • Contact lens use during study drug administration.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: rifabutin
Rifabutin PO [two 150mg capsules] ; Trikafta PO [one orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg]
Drug: Trikafta [orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg]
Subjects will receive a single dose of trikafta (orange tablet) on day 1 of period 1 and on day 15 of period 2.
Drug: Rifabutin 300mg
After washout period greater or equal to 2 days, subjects will receive 300 mg/d of rifabutin on days 1 through 17 of period 2.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
24h area-under the plasma concentration time curve (AUC) of ELX/TEZ/IVA in the absence and the presence of concomitant rifabutin
Time Frame: 22 days
To assess the impact of rifabutin on the AUC of ELX/TEZ/IVA
22 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration (Cmax) of ELX/TEZ/IVA in the absence and the presence of concomitant rifabutin
Time Frame: 22 days
To assess the impact of rifabutin on the Cmax of ELX/TEZ/IVA
22 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Southern California

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Adupa P Rao, M.D., Keck Medicine of USC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 9, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 30, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 12, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 8, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HS-21-00315

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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