Drug Drug InteractionPhase 4NCT04840862
Impact of Rifabutin on the Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor
A Phase 4 study testing Trikafta [orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg] and Rifabutin 300mg in people with Drug Drug Interaction, run by University of Southern California at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Drug Interaction
- What is being tested?
- Trikafta [orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg] and Rifabutin 300mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 9 May 2022to 30 May 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California
Los Angeles, California, 90033
About this study
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.
Read the 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.
- Conditions
- Drug Drug Interaction
- Being tested
- Trikafta [orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg], Rifabutin 300mg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 300mgDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| rifabutin | Experimental | Rifabutin PO [two 150mg capsules] ; Trikafta PO [one orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg] Receives: Drug: Trikafta [orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg]; Drug: Rifabutin 300mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 22 days
Secondary outcomes (1)
Maximum plasma concentration (Cmax) of ELX/TEZ/IVA in the absence and the presence of concomitant rifabutin
To assess the impact of rifabutin on the Cmax of ELX/TEZ/IVA
Measured: 22 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2021
- Study start9 May 2022
- Primary completion30 May 2024
- Study completion30 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug Drug InteractionStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paul Beringer, University of Southern California
- Investigators
- Adupa P Rao, M.D., Study director, Keck Medicine of USC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04840862
- Sponsor's protocol ID
- HS-21-00315
- Status last verified
- Aug 2024
- First submitted
- 7 Apr 2021
- Last updated
- 9 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40957819
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Rifabutin on the Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor
- ClinicalTrials.gov ID
- NCT04840862
- Acronym / sponsor ID
- HS-21-00315
- Conditions
- Drug Drug Interaction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- 9 May 2022 (actual)
- Primary completion
- 30 May 2024 (actual)
- Study completion
- 30 May 2024 (actual)
- First posted
- 12 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| rifabutin | Experimental | Drug: Trikafta [orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg], Drug: Rifabutin 300mgRifabutin PO [two 150mg capsules] ; Trikafta PO [one orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg] |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
| Rifabutin 300mgAfter washout period greater or equal to 2 days, subjects will receive 300 mg/d of rifabutin on days 1 through 17 of period 2. | Drug | rifabutin |
Primary outcome
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
1 secondary outcome
Maximum plasma concentration (Cmax) of ELX/TEZ/IVA in the absence and the presence of concomitant rifabutin
Time frame: 22 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Derived from this study: PubMed 40957819Sanders 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adupa P Rao, M.D. study director
Keck Medicine of USC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Trikafta [orange tablet containing ELX 100mg, TEZ 50mg, and IVA 75mg] and Rifabutin 300mg in people with Drug Drug Interaction, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04840862, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.