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

Condition(s) targeted: Multi-Drug Resistant Tuberculosis; Extensively Drug Resistant Tuberculosis

Intervention: Linezolid (Drug); Microcrystalline Methylcellulose - Placebo (Drug)

Phase: Phase 1/Phase 2

Status: Not yet recruiting

Sponsored by: Centers for Disease Control and Prevention

Official(s) and/or principal investigator(s):
Nesri Padayatchi, MBChB, Principal Investigator, Affiliation: University of KwaZulu
Marc Weiner, MD, Principal Investigator, Affiliation: University of Texas

Overall contact:
Nesri Padayatchi, MBChB, Phone: 27-31-260-4574, Email: padayatchin@ukzn.ac.za

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Pharmacokinetics/Dynamics Study

Primary outcome: Characterize linezolid pharmacokinetic parameters (AUC0-24 and linezolid time over MIC) in patients with MDR-TB and XDR-TB.

Secondary outcome:

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

characterize the pharmacokinetics of ofloxacin and potentially other second line anti-tuberculous drugs utilized in the treatment of patients with MDR TB.

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.

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).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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).

Nesri Padayatchi, MBChB, Phone: 27-31-260-4574, Email: padayatchin@ukzn.ac.za

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

Starting date: March 2009
Ending date: December 2010
Last updated: February 20, 2009