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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 The University of Texas at 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 July 24, 2014