Linezolid Pharmacokinetics (PK) in Multi-Drug Resistant (MDR)/Extensively-Drug Resistant (XDR) Tuberculosis (TB) (S30PK)

This study has been completed.
Sponsor:
Collaborators:
University of Texas
Columbia University
University of KwaZulu
University of Cape Town
Boston University
Pfizer
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00691392
First received: June 3, 2008
Last updated: August 15, 2012
Last verified: August 2012
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Linezolid Pharmacokinetics and Pharmacodynamics in the Treatment of Multi-Drug Resistant and Extensively-Drug Resistant Tuberculosis

Resource links provided by NLM:


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 ]

Enrollment: 26
Study Start Date: April 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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
Other Name: Zyvox
Placebo Comparator: 2
Over-encapsulated microcrystalline methylcellulose (Avicel) - an inert filler
Drug: Microcrystalline Methylcellulose - Placebo
The placebo will be over-encapsulated microcrystalline methylcellulose
Other Name: Avicel

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

Locations
South Africa
King George V Hospital
Durban, KwaZulu Natal, South Africa
Sponsors and Collaborators
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 San Antonio
  More Information

No publications provided

Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT00691392     History of Changes
Other Study ID Numbers: TBTC Study 30PK
Study First Received: June 3, 2008
Last Updated: August 15, 2012
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

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Multidrug-Resistant
Extensively Drug-Resistant Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Linezolid
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014