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TBTC Study 27/28 PK: Moxifloxacin Pharmacokinetics During TB Treatment

Information source: Centers for Disease Control and Prevention
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Tuberculosis

Intervention: moxifloxacin (with isoniazid or ethambutol, rifampin and pyrazinamide) (Drug)

Phase: N/A

Status: Completed

Sponsored by: Centers for Disease Control and Prevention

Official(s) and/or principal investigator(s):
Marc Weiner, MD, Study Chair, Affiliation: VAMC and University of Texas Health Science Center San Antonio
William Burman, MD, Study Chair, Affiliation: Denver Public Health

Summary

This substudy of TBTC Studies 27 and 28 compares 1) the pharmacokinetics of moxifloxacin alone versus moxifloxacin administered with rifampin in healthy volunteers and 2) the pharmacokinetics of moxifloxacin among patients with tuberculosis being treated with multidrug therapy (isoniazid or ethambutol, rifampin, and pyrazinamide) to those of healthy volunteers receiving moxifloxacin plus rifampin. It also evaluates the association between polymorphisms of MDR1 genotype (P-glycoprotein) and rifampin pharmacokinetic parameters, the effect of polymorphisms of MDR1 genotype and/or rifampin pharmacokinetics on isoniazid pharmacokinetic parameters adjusted for N-acetyltransferase genotype (NAT2), and determines by multivariate regression analyses the associations between moxifloxacin or rifampin pharmacokinetic parameters and markers of tuberculosis disease severity including the covariates of two-month culture positivity, cavitary lung disease, Body Mass Index, weight, duration of study treatment prior to PK, co-morbidities and C-reactive protein. Healthy volunteers and TB patients receive frequent scheduled blood draws during a 24 hour period after ingesting a dose of TB drugs.

Clinical Details

Official title: TBTC Study 27/28 PK: Pharmacokinetic Issues in the Use of Moxifloxacin for Treatment of Tuberculosis

Study design: Treatment, Non-Randomized, Double-Blind, Active Control, Parallel Assignment, Pharmacokinetics Study

Primary outcome:

Compare in healthy volunteers the pharmacokinetics of moxifloxacin alone versus moxifloxacin administered with rifampin.

Compare the pharmacokinetics of moxifloxacin among patients with tuberculosis being treated with multidrug therapy (isoniazid or ethambutol, rifampin, and pyrazinamide) to those of healthy volunteers receiving moxifloxacin plus rifampin.

Secondary outcome:

Determine variation of moxifloxacin pharmacokinetics (PK) among patients with pulmonary TB during treatment.

Compare serum concentrations of isoniazid rifampin and pyrazinamide among patients being treated with moxifloxacin versus patients being treated with ethambutol as the fourth drug in multidrug treatment.

Compare serum concentrations of rifampin, pyrazinamide and ethambutol among patients being treated with moxifloxacin versus patients being treated with isoniazid as the fourth drug

Determine the association between polymorphisms of MDR1 genotype (P-glycoprotein) and rifampin PK parameters.

Determine the effect of polymorphisms of MDR1 genotype and/or rifampin PK on isoniazid PK parameters adjusted for N-acetyltransferase genotype (NAT2).

Determine the effects of polymorphisms of MDR1 and UGT genotypes on moxifloxacin PK parameters.

Determine by multivariate regression analyses the associations between moxifloxacin or rifampin PK parameters and markers of disease severity.

Eligibility

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

Criteria:

Inclusion Criteria:

For Healthy Volunteers:

- Provision of informed consent for the study.

- Age > 18 years.

- Willingness to be available for 2 weeks of DOT.

- Willingness to be admitted to a GCRC or hospital on two occasions.

- Women of child-bearing potential must agree to practice an adequate method of birth

control. Barrier methods of contraception or abstinence from sexual activity are satisfactory methods.

- Willingness to have HIV testing done if documented results are not available. (A

prior negative result must be obtained within one year and consists of a negative HIV ELISA. A positive result must be both a positive HIV ELISA and Western Blot, or a plasma HIV PCR RNA level greater than 5000 copies/ml).

- Laboratory screening (if not already available) within 30 days of the first PK

admission:

- Serum potassium within normal limits

- Hematocrit > 35%

- Absolute neutrophil count > 1000 /mm3

- AST < 3 times the upper limit of normal

- Bilirubin < 2 times the upper limit of normal

- Creatinine < 2 times the upper limit of normal

- Eligible and enrolled for medical health care sponsored by the United States federal

government (such as the Veterans Administration enrollment Priority 1 through 7, VHA Directive 2003-003).

For Patients with Tuberculosis Enrolled in TBTC Study 27 or Study 28:

- Any patient enrolled in TBTC Study 27 or Study 28 receiving a daily (5-7 days per

week) regimen.

- Provision of informed consent for the study.

- Willingness to be admitted to a GCRC or hospital on one occasion.

Exclusion Criteria:

For Healthy Volunteers:

- Karnofsky score less than 90

- Pregnancy or breast-feeding. (A negative pregnancy test is required for women of

childbearing potential within 14 days before the first dose of moxifloxacin.)

- Known allergy to any fluoroquinolone or rifamycin antibiotic

- Current or planned therapy during the study with drugs having unacceptable

interactions with rifampin

- History of prolonged QT syndrome or current or planned therapy with quinidine,

procainamide, amiodarone, sotalol, or ziprasidone during period of administration of moxifloxacin and for one week after treatment

For Patients with Tuberculosis Enrolled in TBTC Study 27 or Study 28:

- Severe anemia as defined by a hematocrit less than 25% (most recent value, measured

within 30 days of the PK study).

- History of severe liver disease classified as Child Pugh Class C.

Locations and Contacts

Makerere University Medical School, Kampala, Uganda

University of British Columbia, Vancouver, British Columbia V5Z 1L8, Canada

University of Southern California Medical Center, Los Angeles, California 90033, United States

Johns Hopkins University, Baltimore, Maryland 21231, United States

Duke University Medical Center, Durham, North Carolina 27710, United States

University of North Texas Health Science Center, Fort Worth, Texas 76104, United States

Houston Veterans Administration Medical Center, Houston, Texas 77030, United States

Audie L Murphy Memorial Veterans Administration Medical Center, San Antonio, Texas 78284, United States

Additional Information

Starting date: July 2004
Ending date: August 2007
Last updated: April 18, 2008

Page last updated: June 20, 2008

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