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

Tuberculosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00164463
• Other study ID #: CDC-NCHSTP-4222
• Status: Completed
• Phase: Phase 2
• First received: September 10, 2005
• Last updated: June 7, 2011
• Start date: July 2004
• Est. completion date: August 2007

Study information

• Verified date: June 2011
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: August 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• Moxifloxacin
400 mg po qd 5/7 days per week
• Isoniazid
isoniazid 300 mg po qd 5/7 days per week

Locations

Country	Name	City	State
Canada	University of British Columbia	Vancouver	British Columbia
Uganda	Makerere University Medical School	Kampala
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	University of Southern California Medical Center	Los Angeles	California
United States	Audie L Murphy Memorial Veterans Administration Medical Center	San Antonio	Texas

Sponsors (4)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	Bayer, National Institutes of Health (NIH), VA Office of Research and Development

Countries where clinical trial is conducted

United States,  Canada,  Uganda, 

References & Publications (2)

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. Epub 2007 May 21. — View Citation

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(1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare in healthy volunteers the pharmacokinetics of moxifloxacin alone versus moxifloxacin administered with rifampin.		study period	No
Primary	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.		study period	No
Secondary	Determine variation of moxifloxacin pharmacokinetics (PK) among patients with pulmonary TB during treatment.		study period	No
Secondary	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.		study period	No
Secondary	Compare serum concentrations of rifampin, pyrazinamide and ethambutol among patients being treated with moxifloxacin versus patients being treated with isoniazid as the fourth drug		study period	No
Secondary	Determine the association between polymorphisms of MDR1 genotype (P-glycoprotein) and rifampin PK parameters.		study period	No
Secondary	Determine the effect of polymorphisms of MDR1 genotype and/or rifampin PK on isoniazid PK parameters adjusted for N-acetyltransferase genotype (NAT2).		study period	No
Secondary	Determine the effects of polymorphisms of MDR1 and UGT genotypes on moxifloxacin PK parameters.		study period	No
Secondary	Determine by multivariate regression analyses the associations between moxifloxacin or rifampin PK parameters and markers of disease severity.		study period	No