Pharmacokinetics of Linezolid in Children With Cystic Fibrosis

NCT ID: NCT00625703

Last Updated: 2020-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2011-05-31

Brief Summary

To determine the pharmacokinetic profile of IV (intravenous) and PO (oral) formulations of linezolid among children with cystic fibrosis and establish a dose regimen that will be safe and effective.

Detailed Description

Patients with cystic fibrosis who have pulmonary exacerbations associated with the isolation of Methicillin-resistant Staphylococcus aureus (MRSA) in their sputum will be identified by their primary physicians and by laboratory record review. If they meet the inclusion criteria, they will be invited to participate in the study. The primary outcome variables include pharmacokinetic and pharmacodynamic indices. The study end points include completion of the sputum and blood sampling for pharmacokinetic studies of both intravenous and oral formulations of linezolid and collection of microbiologic specimen (sputum and anterior nares cultures) one month after discharge. Additionally, pharmacokinetic data will be analyzed for effects of age and cystic fibrosis transmembrane conductance regulator (CFTR) mutation on clearance of linezolid and for relationship between levels of linezolid achieved in sputum and blood and clinical outcome

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

A

Group Type: EXPERIMENTAL

Linezolid

Intervention Type: DRUG

Pharmacokinetics

daily dose of linezolid at 15 mg/kg/dose Intravenously (IV) based on subject's weight at study entry, over half an hour period, every 8 hours for a minimum of 7 days to a maximum of 28 days total. The primary doctor may change the route of administration of linezolid from IV to oral (by mouth)after 72 hours on IV formulation and demonstrated clinical improvement based on the clinical evaluation by the primary doctor and comparison of cystic fibrosis exacerbation criteria scores before and after initiating treatment with linezolid.

Interventions

Linezolid

Pharmacokinetics

daily dose of linezolid at 15 mg/kg/dose Intravenously (IV) based on subject's weight at study entry, over half an hour period, every 8 hours for a minimum of 7 days to a maximum of 28 days total. The primary doctor may change the route of administration of linezolid from IV to oral (by mouth)after 72 hours on IV formulation and demonstrated clinical improvement based on the clinical evaluation by the primary doctor and comparison of cystic fibrosis exacerbation criteria scores before and after initiating treatment with linezolid.

Intervention Type: DRUG

Other Intervention Names

Zyvox

Eligibility Criteria

Inclusion Criteria

• Subjects < 18 years of age inclusive, with a confirmed diagnosis of cystic fibrosis being admitted to the hospital for acute pulmonary exacerbation with MRSA isolated from sputum culture.
• Female subject of childbearing potential must have a negative pregnancy test prior to the first dose of study drug, and if sexually active agrees to use an acceptable method of birth control per investigator judgment for the duration of the study.
• Subjects who are receiving medications with serotonergic (such as certain types of antidepressants) and adrenergic activity that can not be discontinued based on clinical judgment of the primary physician may be enrolled. These subjects will be monitored closely for serotonin- and sympathomimetic-associated toxicity.
• Subject (when able) and subject's parent /legal guardian agree to comply with the study requirements.
• Subject has sufficient venous access to permit administration of the study medication, collection of pharmacokinetic samples and monitoring of safety variables.
• Duration of linezolid therapy is expected to exceed 7 days.
• English and Spanish-speaking subjects.

Exclusion Criteria

• Subjects with clinical or laboratory evidence of severe hepatic (Child-Pugh class C) disease
• Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min)
• Subjects with a history of allergy to linezolid.
• Pregnant and breastfeeding subjects.

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jane Siegel, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Southwestern Medical Center at Dallas

Locations

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Countries

United States

Other Identifiers

IRB File # 112007-010

Identifier Type: -

Identifier Source: org_study_id