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

Phase 1

Completed

• Conditions: Multi-Drug Resistant Tuberculosis; Extensively Drug Resistant Tuberculosis
• Interventions: Drug: Microcrystalline Methylcellulose - Placebo; Drug: Linezolid

• Registration Number: NCT00691392
• Lead Sponsor: Centers for Disease Control and Prevention

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2008-06-03
• Study First Submitted QC: 2008-06-04
• Study First Posted: 2008-06-05
• Study Start: 2009-04
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Status Verified: 2012-08
• Last Update Submitted: 2012-08-15
• Last Update Posted: 2012-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Microcrystalline Methylcellulose - Placebo	Over-encapsulated microcrystalline methylcellulose (Avicel) - an inert filler
1	Linezolid	Linezolid 600 mg po daily for 16 weeks (112 doses) given in addition to optimized background therapy for MDR TB

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

King George V Hospital; 🇿🇦 Durban, KwaZulu Natal, South Africa