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.
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
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
6
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.
University of Southern California
Los Angeles, California, United States
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
Time frame: 22 days
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
Time frame: 22 days
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