Clinical trial NCT00691392: Linezolid Pharmacokinetics (PK) in Multi-Drug Resistant (MDR)/Extensively-Drug Resistant (XDR) Tuberculosis (TB)
Official title: Linezolid Pharmacokinetics and Pharmacodynamics in the Treatment of Multi-Drug Resistant and Extensively-Drug Resistant Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multi-Drug Resistant Tuberculosis
Extensively Drug Resistant Tuberculosis
Keywords: Multi-Drug Resistant Tuberculosis
Extensively Drug Resistant Tuberculosis
MDR TB
XDR TB
MDR
XDR
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: University of Texas
name: Columbia University
name: University of KwaZulu
name: University of Cape Town
name: Boston University
name: Pfizer
First posted: 2008-06-05
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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).

Primary outcomes:
measure: Characterize linezolid pharmacokinetic parameters (AUC0-24 and linezolid time over MIC) in patients with MDR-TB and XDR-TB.
timeFrame: 1 month after the start of study therapy
Secondary outcomes:
measure: 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
timeFrame: 20 weeks after starting study therapy
measure: characterize the pharmacokinetics of ofloxacin and potentially other second line anti-tuberculous drugs utilized in the treatment of patients with MDR TB.
timeFrame: one month after starting study therapy
measure: 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.
timeFrame: 16 weeks after starting study therapy
Other outcomes:
Locations:
city: Durban
country: South Africa
facility: King George V Hospital
state: KwaZulu Natal
Study officials:
affiliation: University of KwaZulu
name: Nesri Padayatchi, MBChB
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas at San Antonio
name: Marc Weiner, MD
role: PRINCIPAL_INVESTIGATOR
References: