Pharmacokinetics of Linezolid in Children With Cystic Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Linezolid

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

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center at Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: A

Drug: 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.; Other Names: Zyvox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine the Pharmacokinetic Profile of IV (Intravenous) and PO (Oral) Formulations of Linezolid Among Children With Cystic Fibrosis	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.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Exacerbations With Methicillin Resistant Staphylococcus Aureus (MRSA) to Treatment With Linezolid	to characterize the clinical response of children with pulmonary exacerbations (increase in the severity of the patient's lung symptoms) associated with methicillin resistant Staphylococcus aureus (MRSA) to treatment with linezolid	2 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Jane Siegel, MD, University of Texas, Southwestern Medical Center at Dallas

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: February 19, 2008
• First Submitted That Met QC Criteria: February 27, 2008
• First Posted (ESTIMATE): February 28, 2008

Study Record Updates

• Last Update Posted (ACTUAL): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 13, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetic
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid
• Other Study ID Numbers: IRB File # 112007-010