Linezolid Pharmacokinetics (PK) in Multi-Drug Resistant (MDR)/Extensively-Drug Resistant (XDR) Tuberculosis (TB) - Full Text View

Sponsor:	Centers for Disease Control and Prevention
Collaborators:	University of Texas Columbia University University of KwaZulu University of Cape Town Boston University Pfizer
Information provided by (Responsible Party):	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00691392

Purpose

This is a one-period, double-blind, single-center pharmacokinetic study of linezolid in patients with MDR or XDR tuberculosis treated with linezolid and an Optimized Background Therapy (defined as treatment with > 4 drugs with activity against tuberculosis to which the patient's isolate is believed to be sensitive by history or based on drug sensitivity testing).

Condition	Intervention	Phase
Multi-Drug Resistant Tuberculosis Extensively Drug Resistant Tuberculosis	Drug: Linezolid Drug: Microcrystalline Methylcellulose - Placebo	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Linezolid Pharmacokinetics and Pharmacodynamics in the Treatment of Multi-Drug Resistant and Extensively-Drug Resistant Tuberculosis

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Drug Information available for: Cellulose sodium phosphate Linezolid Cellulose Methylcellulose Phosphocellulose

U.S. FDA Resources

Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:

Characterize linezolid pharmacokinetic parameters (AUC0-24 and linezolid time over MIC) in patients with MDR-TB and XDR-TB. [ Time Frame: 1 month after the start of study therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assess the pharmacodynamic effects of linezolid AUC0-24 on tolerability (bone marrow toxicity, peripheral and ocular neuropathies) and safety during four months of treatment of tuberculosis [ Time Frame: 20 weeks after starting study therapy ] [ Designated as safety issue: Yes ]
characterize the pharmacokinetics of ofloxacin and potentially other second line anti-tuberculous drugs utilized in the treatment of patients with MDR TB. [ Time Frame: one month after starting study therapy ] [ Designated as safety issue: No ]
Assess the pharmacodynamic effect of linezolid pharmacokinetic parameters ( on biomarkers of treatment activity. Biomarkers to be evaluated are time to detection in liquid culture, sputum culture conversion at two and four months of study treatment. [ Time Frame: 16 weeks after starting study therapy ] [ Designated as safety issue: No ]

Enrollment:	26
Study Start Date:	April 2009
Study Completion Date:	May 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Linezolid 600 mg po daily for 16 weeks (112 doses) given in addition to optimized background therapy for MDR TB	Drug: Linezolid Linezolid 600 mg po daily for 16 weeks (112 doses) - over-encapsulated Other Name: Zyvox
Placebo Comparator: 2 Over-encapsulated microcrystalline methylcellulose (Avicel) - an inert filler	Drug: Microcrystalline Methylcellulose - Placebo The placebo will be over-encapsulated microcrystalline methylcellulose Other Name: Avicel

Detailed Description:

This is a one-period, double-blind, single-center pharmacokinetic study of linezolid in patients with MDR or XDR tuberculosis treated with linezolid and an Optimized Background Therapy (defined as treatment with > 4 drugs with activity against tuberculosis to which the patient's isolate is believed to be sensitive by history or based on drug sensitivity testing).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Enrolled in the TBTC Study 30
Provision of informed consent for the study

Exclusion Criteria:

Severe anemia as defined by a hematocrit less than 25% (most recent value, measured within 30 days of the PK study).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00691392

Locations

South Africa
King George V Hospital
Durban, KwaZulu Natal, South Africa

Sponsors and Collaborators

Centers for Disease Control and Prevention

University of Texas

Columbia University

University of KwaZulu

University of Cape Town

Boston University

Pfizer

Investigators

Principal Investigator:	Nesri Padayatchi, MBChB	University of KwaZulu
Principal Investigator:	Marc Weiner, MD	University of Texas

More Information

No publications provided

Responsible Party:	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00691392 History of Changes
Other Study ID Numbers:	TBTC Study 30PK
Study First Received:	June 3, 2008
Last Updated:	October 7, 2011
Health Authority:	United States: Food and Drug Administration; South Africa: Medicines Control Council

Keywords provided by Centers for Disease Control and Prevention:

Multi-Drug Resistant Tuberculosis
Extensively Drug Resistant Tuberculosis
MDR TB

XDR TB
MDR
XDR

Additional relevant MeSH terms:

Tuberculosis
Tuberculosis, Multidrug-Resistant
Extensively Drug-Resistant Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

Linezolid
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012