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

NCT04840862 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: HS-21-00315
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Drug Interaction

Outcome Measures

Primary Outcomes (1)

• 24h area-under the plasma concentration time curve (AUC) of ELX/TEZ/IVA in the absence and the presence of concomitant rifabutin

  To assess the impact of rifabutin on the AUC of ELX/TEZ/IVA

  22 days

Secondary Outcomes (1)

• Maximum plasma concentration (Cmax) of ELX/TEZ/IVA in the absence and the presence of concomitant rifabutin

  22 days

Study Arms (1)

rifabutin

EXPERIMENTAL

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]; Drug: Rifabutin 300mg

Interventions

Trikafta [orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg] DRUG

Subjects will receive a single dose of trikafta (orange tablet) on day 1 of period 1 and on day 15 of period 2.

rifabutin

Rifabutin 300mg DRUG

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.

rifabutin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

University of Southern California

Los Angeles, California, 90033, United States

Location

Related Publications (1)

• Sanders M, Hong E, Chung PS, Rao AP, Cohn W, Beringer P. Evaluation of the drug interaction between rifabutin and elexacaftor/tezacaftor/ivacaftor (ETI). J Cyst Fibros. 2026 Jan;25(1):151-157. doi: 10.1016/j.jcf.2025.09.002. Epub 2025 Sep 16.

  PMID: 40957819 DERIVED

MeSH Terms

Interventions

elexacaftor, ivacaftor, tezacaftor drug combination; Rifabutin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Adupa P Rao, M.D.

  Keck Medicine of USC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Pharmacy

Model Details: A single group of subjects will receive a single dose of trikafta (orange tablet) in period 1. After washout period greater or equal to 2 days, subjects will receive 300 mg/d of rifabutin on day 1 through 17 and a single dose of trikafta (orange tablet) on day 15 in period 2.

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 12, 2021
• Study Start: May 9, 2022
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: August 9, 2024

Record last verified: 2024-08

Locations

US (1)