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

NCT ID: NCT00164463

Last Updated: 2011-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2007-08-31

Brief 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.

Conditions

Tuberculosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Moxifloxacin

Moxifloxacin 400 mg po qd given 5 of 7 days per week

Group Type: EXPERIMENTAL

Moxifloxacin

Intervention Type: DRUG

400 mg po qd 5/7 days per week

Isoniazid

Isoniazid 300 mg po qd given 5/7 days per week

Group Type: ACTIVE_COMPARATOR

Isoniazid

Intervention Type: DRUG

isoniazid 300 mg po qd 5/7 days per week

Interventions

Moxifloxacin

400 mg po qd 5/7 days per week

Intervention Type: DRUG

Isoniazid

isoniazid 300 mg po qd 5/7 days per week

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

US Department of Veterans Affairs

FED

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: lead

Responsible Party

Tuberculosis Trial Consortium

Principal Investigators

Marc Weiner, MD

Role: STUDY_CHAIR

VAMC and University of Texas Health Science Center San Antonio

William Burman, MD

Role: STUDY_CHAIR

Denver Public Health

Locations

University of Southern California Medical Center

Los Angeles, California, United States

Johns Hopkins University

Baltimore, Maryland, United States

Duke University Medical Center

Durham, North Carolina, United States

University of North Texas Health Science Center

Fort Worth, Texas, United States

Houston Veterans Administration Medical Center

Houston, Texas, United States

Audie L Murphy Memorial Veterans Administration Medical Center

San Antonio, Texas, United States

University of British Columbia

Vancouver, British Columbia, Canada

Makerere University Medical School

Kampala, , Uganda

Countries

United States; Canada; Uganda

References

Weiner M, Peloquin C, Burman W, Luo CC, Engle M, Prihoda TJ, Mac Kenzie WR, Bliven-Sizemore E, Johnson JL, Vernon A. Effects of tuberculosis, race, and human gene SLCO1B1 polymorphisms on rifampin concentrations. Antimicrob Agents Chemother. 2010 Oct;54(10):4192-200. doi: 10.1128/AAC.00353-10. Epub 2010 Jul 26.

Reference Type: RESULT

PMID: 20660695 (View on PubMed)

Weiner M, Burman W, Luo CC, Peloquin CA, Engle M, Goldberg S, Agarwal V, Vernon A. Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Antimicrob Agents Chemother. 2007 Aug;51(8):2861-6. doi: 10.1128/AAC.01621-06. Epub 2007 May 21.

Reference Type: RESULT

PMID: 17517835 (View on PubMed)

Weiner M, Gelfond J, Johnson-Pais TL, Engle M, Peloquin CA, Johnson JL, Sizemore EE, Mac Kenzie WR. Elevated Plasma Moxifloxacin Concentrations and SLCO1B1 g.-11187G>A Polymorphism in Adults with Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e01802-17. doi: 10.1128/AAC.01802-17. Print 2018 May.

Reference Type: DERIVED

PMID: 29463526 (View on PubMed)

Other Identifiers

CDC-NCHSTP-4222

Identifier Type: -

Identifier Source: org_study_id