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

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

Official Title
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Linezolid Pharmacokinetics and Pharmacodynamics in the Treatment of Multi-Drug Resistant and Extensively-Drug Resistant Tuberculosis

Conditions
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Multi-Drug Resistant Tuberculosis, Extensively Drug Resistant Tuberculosis

Intervention / Treatment
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* Drug: Linezolid
* Drug: Microcrystalline Methylcellulose - Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Linezolid 600 mg po daily for 16 weeks (112 doses) given in addition to optimized background therapy for MDR TB | Drug: Linezolid<br>* Linezolid 600 mg po daily for 16 weeks (112 doses) - over-encapsulated<br>* Other names: Zyvox;|
| Placebo Comparator: 2<br>Over-encapsulated microcrystalline methylcellulose (Avicel) - an inert filler | Drug: Microcrystalline Methylcellulose - Placebo<br>* The placebo will be over-encapsulated microcrystalline methylcellulose<br>* Other names: Avicel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize linezolid pharmacokinetic parameters (AUC0-24 and linezolid time over MIC) in patients with MDR-TB and XDR-TB. |  | 1 month after the start of study therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 20 weeks after starting study therapy | 
| characterize the pharmacokinetics of ofloxacin and potentially other second line anti-tuberculous drugs utilized in the treatment of patients with MDR TB. |  | one month after starting study therapy | 
| 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. |  | 16 weeks after starting study therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDR, Multi-Drug Resistant Tuberculosis, Extensively Drug Resistant Tuberculosis, MDR TB, XDR TB, XDR