Pharmacokinetics of Linezolid in Children With Cystic Fibrosis - Full Text View

Sponsor:	University of Texas Southwestern Medical Center
Collaborator:	Cystic Fibrosis Foundation
Information provided by:	University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00625703

Purpose

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.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: Linezolid	Phase II

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics Study
Official Title:	Pharmacokinetics of Linezolid in Children With Cystic Fibrosis

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Linezolid

U.S. FDA Resources

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:

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. [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	14
Study Start Date:	May 2008
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental	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.

Arms

Assigned Interventions

A: Experimental

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.

Detailed Description:

Patients with cystic fibrosis who have pulmonary exacerbations associated with the isolation of 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 CFTR mutation on clearance of linezolid and for relationship between levels of linezolid achieved in sputum and blood and clinical outcome

Eligibility

Ages Eligible for Study:	up to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625703

Contacts

Contact: Jane Siegel, MD.	214-648-3720	jane.siegel@utsouthwestern.edu
Contact: Chonnamet Techasaensiri, MD	214-648-3720	chonnamet.techasaensiri@utsouthwestern.edu

Locations

United States, Texas
University of Texas Southwestern Medical Center at Dallas	Recruiting
Dallas, Texas, United States, 75390
Contact: Jane Siegel, MD 214-648-3720 jane.siegel@utsouthwestern.edu
Contact: Chonnamet Techasaensiri, MD 214-648-3720 chonnamet.techasensiri@utsouthwestern.edu
Sub-Investigator: Roberto Santos, MD
Sub-Investigator: Claude Prestidge, MD
Sub-Investigator: Michael E Brown, MD
Sub-Investigator: Chonnamet Techasaensiri, MD
Sub-Investigator: Pablo J. Sanchez, MD
Sub-Investigator: Steven Copenhaver, MD
Sub-Investigator: Andrew Gelfand, MD

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Cystic Fibrosis Foundation

Investigators

Principal Investigator:

Jane Siegel, MD

University of Texas Southwestern Medical Center at Dallas

More Information

No publications provided

Responsible Party:	University of Texas Southwestern Medical Center at Dallas ( Jane Siegel, MD )
Study ID Numbers:	IRB File # 112007-010
Study First Received:	February 19, 2008
Last Updated:	January 21, 2009
ClinicalTrials.gov Identifier:	NCT00625703 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:

Pharmacokinetic

Additional relevant MeSH terms:

Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Fibrosis
Enzyme Inhibitors
Pharmacologic Actions
Protein Synthesis Inhibitors
Digestive System Diseases
Pathologic Processes

Cystic Fibrosis
Respiratory Tract Diseases
Genetic Diseases, Inborn
Lung Diseases
Therapeutic Uses
Pancreatic Diseases
Infant, Newborn, Diseases
Linezolid

ClinicalTrials.gov processed this record on February 08, 2010