Background: Tezacaftor/ivacaftor is a new treatment option in many regions for patients aged ≥12 years who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function (F/RF) mutation. This Phase 3, 2-part, open-label study evaluated the pharmacokinetics (PK), safety, tolerability, and efficacy of tezacaftor/ivacaftor in children aged 6 through 11 years with these mutations. Methods: Part A informed weight-based tezacaftor/ivacaftor dosages for part B. The primary objective of part B was to evaluate the safety and tolerability of tezacaftor/ivacaftor through 24 weeks; the secondary objective was to evaluate efficacy based on changes from baseline in percentage predicted forced expiratory volume in 1 s (ppFEV 1 ), growth parameters, sweat chloride, and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. Results: After PK analysis in part A, 70 children received ≥1 dose of tezacaftor/ivacaftor in part B; 67 children completed treatment. Exposures in children aged 6 through 11 years were within the target range for those observed in patients aged ≥12 years. The safety profile of tezacaftor/ivacaftor was generally similar to prior studies in patients aged ≥12 years. One child discontinued treatment for a serious adverse event of constipation. Tezacaftor/ ivacaftor treatment improved sweat chloride levels and CFQ-R respiratory domain scores, mean ppFEV 1 remained stable in the normal range, and growth parameters remained stable over 24 weeks. Conclusions: Tezacaftor/ivacaftor was generally safe and well tolerated, and improved CFTR function in children aged 6 through 11 years with CF with F/F and F/RF genotypes, supporting tezacaftor/ivacaftor use in this age group. NCT02953314.

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People with cystic fibrosis (CF) are highly susceptible to bacterial infections of the airways. By adulthood, chronic Pseudomonas aeruginosa ( Pa) is the most prevalent infective organism and is difficult to eradicate owing to its adaptation to the CF lung microenvironment. Long-term suppressive treatment with inhaled antimicrobials is the standard care for reducing exacerbation frequency, improving quality of life and increasing measures of lung function. Levofloxacin (a fluoroquinolone antimicrobial) has been approved as an inhaled solution in Europe and Canada, for the treatment of adults with CF with chronic P. aeruginosa pulmonary infections. Here, we review the clinical principles relating to the use of inhaled antimicrobials and inhaled levofloxacin for the management of P. aeruginosa infections in patients with CF.

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