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

Sponsors and Collaborators:	Centers for Disease Control and Prevention University of Texas Columbia University University of KwaZulu University of Cape Town Boston University Pfizer
Information provided by:	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

MedlinePlus related topics: Tuberculosis

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Linezolid Pharmacokinetics and Pharmacodynamics in the Treatment of Multi-Drug Resistant and Extensively-Drug Resistant Tuberculosis

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 ]

Estimated Enrollment:	50
Study Start Date:	October 2008
Estimated Study Completion Date:	October 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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
2: Placebo Comparator Over-encapsulated microcrystalline methylcellulose (Avicel) - an inert filler	Drug: Microcrystalline Methylcellulose - Placebo The placebo will be over-encapsulated microcrystalline methylcellulose

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

Contacts

Contact: Nesri Padayatchi, MBChB	27-31-260-4574	padayatchin@ukzn.ac.za
Contact: Nelisiwe Mnguni, RN	27-83-465-8785	mngunin3@ukzn.ac.za

Locations

South Africa, KwaZulu Natal
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

Responsible Party:	Centers for Disease Control and Prevention ( William R. Mac Kenzie MD/Project Officer )
Study ID Numbers:	TBTC Study 30PK
Study First Received:	June 3, 2008
Last Updated:	June 4, 2008
ClinicalTrials.gov Identifier:	NCT00691392
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

Study placed in the following topic categories:

Bacterial Infections
Gram-Positive Bacterial Infections
Tuberculosis, Multidrug-Resistant
Mycobacterium Infections

Extensively Drug-Resistant Tuberculosis
Tuberculosis
Linezolid

Additional relevant MeSH terms:

Protein Synthesis Inhibitors
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Enzyme Inhibitors
Pharmacologic Actions
Actinomycetales Infections

ClinicalTrials.gov processed this record on January 15, 2009