- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04840862
Impact of Rifabutin on the Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor
February 20, 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
Recruiting
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Estimated)
24
Phase
- 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
- Name: Paul M. Beringer, PharmD
- Phone Number: 323-442-1402
- Email: beringer@usc.edu
Study Locations
-
-
California
-
Los Angeles, California, United States, 90033
- Recruiting
- University of Southern California
-
Contact:
- Paul M. Beringer, PharmD
- Phone Number: 323-442-1402
- Email: beringer@usc.edu
-
-
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
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 |
Intervention / Treatment |
---|---|
Experimental: rifabutin
Rifabutin PO [two 150mg capsules] ; Trikafta PO [one 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.
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
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
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.
Investigators
- 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)
May 9, 2022
Primary Completion (Estimated)
May 1, 2024
Study Completion (Estimated)
May 1, 2024
Study Registration Dates
First Submitted
April 7, 2021
First Submitted That Met QC Criteria
April 7, 2021
First Posted (Actual)
April 12, 2021
Study Record Updates
Last Update Posted (Actual)
February 22, 2024
Last Update Submitted That Met QC Criteria
February 20, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID 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.
Clinical Trials on Drug Drug Interaction
-
Hutchison Medipharma LimitedCompletedFood-drug Interaction | Drug InteractionUnited States
-
Daewoong Pharmaceutical Co. LTD.Active, not recruitingDrug Drug InteractionKorea, Republic of
-
Daewoong Pharmaceutical Co. LTD.Enrolling by invitationDrug-drug InteractionKorea, Republic of
-
Daewoong Pharmaceutical Co. LTD.CompletedDrug Drug InteractionKorea, Republic of
-
ItalfarmacoCompletedDrug-Drug InteractionPortugal
-
Aurinia Pharmaceuticals Inc.CompletedDrug-drug InteractionUnited States
-
Blade TherapeuticsCompletedDrug Drug InteractionUnited States
-
Daewoong Pharmaceutical Co. LTD.CompletedDrug-drug InteractionAustralia
-
Nanjing Yoko Biomedical Co., Ltd.CompletedDrug-drug InteractionChina
-
Repros Therapeutics Inc.CompletedDrug-drug InteractionUnited States