Pharmacokinetics of Antibiotics in Patients With Cystic Fibrosis Trated With Elexacaftor/Tezacaftor/Ivacaftor (ETI) (PKCF)

Cystic fibrosis (CF) is associated with major pharmacokinetic and pharmacodynamic alterations affecting antibiotic exposure, including changes in absorption, distribution, metabolism, and elimination. Historically, these alterations justified the use of higher antibiotic doses in CF patients in order to achieve therapeutic concentrations and improve pulmonary outcomes.

The advent of highly effective CFTR modulators, particularly the triple combination elexacaftor/tezacaftor/ivacaftor (ETI), has substantially improved pulmonary function, nutritional status, inflammatory burden, and quality of life in patients with CF. ETI therapy also appears to modify respiratory microbiology and reduce the frequency of pulmonary exacerbations.

These clinical and physiological improvements may alter antibiotic pharmacokinetics and pharmacodynamics in patients with CF, potentially making current high-dose antibiotic recommendations less appropriate for some patients. Since repeated exposure to high-dose antibiotics is associated with cumulative toxicities, particularly aminoglycoside-related ototoxicity and nephrotoxicity, reassessment of antibiotic dosing strategies is warranted.

The PKCF study is a multicenter, prospective, observational, non-interventional study designed to characterize the pharmacokinetic profiles of intravenous antibiotics administered during pulmonary exacerbations in adolescents and adults with cystic fibrosis receiving ETI therapy.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis (CF); Respiratory Infection Bacterial; Pulmonary Exacerbation
• Intervention / Treatment: Other: No intervention assigned

Detailed Description

Patients with cystic fibrosis experience substantial physiological changes that affect the pharmacokinetics of medications, including antibiotics. Altered gastrointestinal absorption, increased volume of distribution, enhanced renal clearance, chronic systemic inflammation, and modified protein binding have historically led to recommendations for increased antibiotic dosing in CF patients.

Additionally, thick airway mucus, biofilm formation, high bacterial inoculum, and chronic airway infection contribute to altered antibiotic pharmacodynamics and reduced antibiotic efficacy.

Highly effective CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), have profoundly changed the clinical course of cystic fibrosis by improving lung function, reducing pulmonary exacerbations, improving nutritional status, and modifying airway microbiology. These changes may normalize or partially normalize antibiotic pharmacokinetics and pharmacodynamics.

However, evidence regarding the impact of ETI therapy on antibiotic pharmacokinetics remains extremely limited. To date, only one retrospective pediatric study has evaluated the effect of CFTR modulators on intravenous tobramycin pharmacokinetics during pulmonary exacerbations.

The PKCF study aims to prospectively evaluate plasma antibiotic concentrations and pharmacokinetic parameters in CF patients receiving ETI during pulmonary exacerbations requiring antibiotic therapy. Antibiotic concentrations will be compared with established PK/PD targets according to current national recommendations.

The study may contribute to future optimization of antibiotic dosing strategies in patients with CF treated with ETI, while minimizing toxicity and supporting antimicrobial stewardship.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Matthieu Pichelin; Email: matthieu.pichelin@ildys.org
• Study Contact Backup: Name: Marion Buyse, PharmD, PhD; Phone Number: +33298293447; Email: marion.buyse@ildys.org

Study Locations

• France
  • Roscoff, France, 29680
    • Recruiting
    • Fondation ILDYS
    • Contact: Marion Buyse, PharmD; PhD; Phone Number: 0298293447; Email: marion.buyse@ildys.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

CF patients

Description

Inclusion Criteria:

• Diagnosis of cystic fibrosis confirmed by sweat test and/or genetic testing
• Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least 3 months
• Age 12 years or older
• Patient informed and not objecting to participation; for minors, parents/legal guardians informed and not objecting to participation
• Clinical indication for antibiotic therapy for pulmonary exacerbation or respiratory infection according to treating physician
• Affiliation to a social security system

Exclusion Criteria:

• Lung transplantation or heart-lung transplantation
• Patients under guardianship or curatorship
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy; Patients with cystic fibrosis treated with ETI receiving antibiotic therapy for pulmonary exacerbation	Other: No intervention assigned; Routine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment	Plasma antibiotic concentrations will be measured at Day 3 of treatment to determine pharmacokinetic parameters including: Cmax (maximum plasma concentration); Cmin (minimum plasma concentration) Pharmacokinetic/pharmacodynamic ratios will be evaluated according to bacterial minimum inhibitory concentrations (MICs): Cmin/MIC ratio for time-dependent antibiotics; Cmax/MIC ratio for concentration-dependent antibiotics Antibiotic exposure will be compared with PK/PD targets validated by national expert recommendations.	Day 3 of antibiotic therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical efficacy: body weight evolution	the Clinical parameters body weight in kilograms	Baseline, Day 3, Day 7-10, and end of antibiotic treatment
Clinical efficacy: temperature evolution	the Clinical parameters temperature in celsius degree	Baseline, Day 3, Day 7-10, and end of antibiotic treatment
Clinical efficacy: appetite evolution	the Clinical parameters "appetite" will be score on a scale from 0 to 10 with higher score mean worse outcome	Baseline, Day 3, Day 7-10, and end of antibiotic treatment
Clinical efficacy: fatigue evolution	the Clinical parameters "fatigue" will be score on a scale from 0 to 10 with higher score mean worse outcome	Baseline, Day 3, Day 7-10, and end of antibiotic treatment
Clinical efficacy: dyspnea evolution	the Clinical parameters "dyspnea" will be score on a scale from 0 to 10 with higher score mean worse outcome	Baseline, Day 3, Day 7-10, and end of antibiotic treatment
Clinical efficacy: sputum volume	the Clinical parameters "sputum volume" will be score on a scale from 0 to 10 with higher score mean worse outcome	Baseline, Day 3, Day 7-10, and end of antibiotic treatment
Clinical efficacy: sputum purulence	the Clinical parameters "sputum purulence" will be score on a scale from 0 to 10 with higher score mean worse outcome	Baseline, Day 3, Day 7-10, and end of antibiotic treatment
biological evolution: Renal function evolution	renal function will be evaluated by measuring plasma creatinine and calculated glomerular filtration rate	Baseline, Day 3, and end of antibiotic treatment
biological evolution: inflammatory markers	inflammation will be evaluated by measuring plasma c protein reactive and plasma leukocytes concentration	Baseline, Day 3, and end of antibiotic treatment
Treatment adherence	Treatment adherence will be evaluated by the ratio of antibiotic doses administered to doses prescribed	through study completion, an average 14 days
number of participants with treatment-related adverse events	Adverse events related to antibiotic therapy will be collected and graded according to NCI CTCAE version 6.0	through study completion, an average 14 days

Collaborators and Investigators

• Sponsor: Fondation Ildys

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: May 15, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Antibiotics; Cystic Fibrosis; Pulmonary Exacerbation; Therapeutic drug monitoring; CFTR modulators; Elexacaftor/Tezacaftor/Ivacaftor
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis
• Other Study ID Numbers: RI2025-016; 2025-A02333-46 (Other Identifier: IDRCB Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No