Pharmacokinetics of Linezolid in Children With Cystic Fibrosis

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00625703
• Collaborator: Cystic Fibrosis Foundation (Other)
• Enrollment: 45
• Location: 1
• Arm: 1
• Duration (Months): 5
• Patients Per Site Per Month: 9.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Linezolid	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Pharmacokinetics of Linezolid in Children With Cystic Fibrosis
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. To Determine the Pharmacokinetic Profile of IV (Intravenous) and PO (Oral) Formulations of Linezolid Among Children With Cystic Fibrosis [2 months]

   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.

Secondary Outcome Measures

1. Pulmonary Exacerbations With Methicillin Resistant Staphylococcus Aureus (MRSA) to Treatment With Linezolid [2 months]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00625703
• Other Study ID Numbers: IRB File # 112007-010
• First Posted: Feb 28, 2008
• Last Update Posted: Mar 27, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by University of Texas Southwestern Medical Center: Pharmacokinetic
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Linezolid

Study Results

Participant Flow

Pre-assignment Detail	No data available as PI is no longer at the institution. Several attempts were made to locate the PI or other study personnel associated with this study, but they were unsuccessful. Enrollment reflects the anticipated enrollment and actual enrollment is unknown due to PI is no longer at the institution.

Arm/Group Title	Linezolid: Pharmacokinetics
Arm/Group Description	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.
Period Title: Overall Study
STARTED	0
COMPLETED	0
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Linezolid: Pharmacokinetics
Arm/Group Description	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.
Overall Participants	0
Overall participants	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Sex: Female, Male () []
Female
Male

Outcome Measures

1. Primary Outcome

Title	To Determine the Pharmacokinetic Profile of IV (Intravenous) and PO (Oral) Formulations of Linezolid Among Children With Cystic Fibrosis
Description	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

Outcome Measure Data

Analysis Population Description

No data are available as PI is no longer at the institution. Several attempts were made to locate the PI or other study personnel associated with this study, but they were unsuccessful

Arm/Group Title	Linezolid: Pharmacokinetics
Arm/Group Description	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.
Measure Participants	0

2. Secondary Outcome

Title	Pulmonary Exacerbations With Methicillin Resistant Staphylococcus Aureus (MRSA) to Treatment With Linezolid
Description	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

Outcome Measure Data

Analysis Population Description

No data are available as PI is no longer at the institution. Several attempts were made to locate the PI or other study personnel associated with this study, but they were unsuccessful

Arm/Group Title	Linezolid: Pharmacokinetics
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	No data are available as PI is no longer at the institution. Several attempts were made to locate the PI or other study personnel associated with this study, but they were unsuccessful
Arm/Group Title	Linezolid: Pharmacokinetics
Arm/Group Description	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.
All Cause Mortality
	Linezolid: Pharmacokinetics
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Linezolid: Pharmacokinetics
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Investigations
Data not available	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Linezolid: Pharmacokinetics
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Investigations
No Data Available	0/0 (NaN)	0

Limitations/Caveats

No data are available as PI is no longer at the institution. Several attempts were made to locate the PI or other study personnel associated with this study, but they were unsuccessful.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.