TBTC Study 26 PK: Rifapentine Pharmacokinetics in Children During Treatment of Latent TB Infection

NCT ID: NCT00164450

Last Updated: 2008-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2008-08-31

Brief Summary

Compared to adults, children appear to require higher weight-based doses of rifapentine to acheive comparable drug levels. TBTC Study 26, a study of the effectiveness and tolerability of weekly rifapentine/isoniazid for three months versus daily isoniazid for nine months for the treatment of latent tuberculosis infection, has been amended to include children ages 2-11 based on an initial single-dose study and pharmacokinetic modeling. Study 26PK evaluates the adequacy of the doses chosen for young children enrolled in Study 26 with a single blood draw, 24 hours after the third or subsequent weekly Study 26 dose of rifapentine and isoniazid. An adult control is enrolled for each child enrolled.

Detailed Description

The pharmacokinetics of rifapentine have been studied in adults, adolescents (ages 12-15 years), and patients with hepatic dysfunction and HIV infection. However, there are no published data on the efficacy, safety or pharmacokinetics of rifapentine in children. This lack of data has precluded till now enrollment of children less than 12 years old in TBTC Study 26, a study of the effectiveness and tolerability of weekly rifapentine/isoniazid for three months versus daily isoniazid for nine months for the treatment of latent tuberculosis infection, a phase 3 treatment trial that will enroll 8000 persons with latent tuberculosis infection. A recently completed initial evaluation of rifapentine pharmacokinetics among children receiving a single dose of rifapentine demonstrated significantly lower exposures of rifapentine among children compared to adults, when children were given weight-based doses chosen to be comparable to a 600 mg oral dose in adults. This reduced exposure suggested that children require higher weight-based doses than adults and a model was constructed to estimate rifapentine doses in children that would result in exposures similar to the 900 mg dose used for adults in Study 26. Study 26 has been amended to include children ages 2-11 based on the initial single-dose study and pharmacokinetic modeling. The purpose of Study 26PK is to evaluate the adequacy of the doses chosen for young children who enrolled in Study 26.

Briefly, this study aims to:

• determine whether rifapentine exposure is equivalent in young children receiving weight-based dosing to adults receiving 900 mg.
• correlate rifapentine exposure with toxicity in young children
• validate accuracy of weight-based dosing in children
• determine rifapentine bioavailability in children
• determine association in adults between polymorphisms of MDR1 genotype and rifapentine exposure
• correlate isoniazid concentrations in adults with acetylator status

Conditions

Tuberculosis

Keywords

tuberculosis; TB; pharmacokinetics; children

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Rifapentine + isoniazid once weekly for 3 months

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Enrolled in TBTC Study 26 randomized to treatment with once weekly isoniazid and rifapentine:

• Child between the ages of 2 to less than 12 years for whom informed consent by a guardian and of assent (if applicable) have been obtained.
• Adult greater than age 18 for whom informed consent has been obtained.

2. Willingness to undergo a blood phlebotomy 24 hours following dosing of isoniazid and rifapentine after receiving at least three once-weekly doses of rifapentine plus isoniazid.

If as a result of a contact investigation, both a parent and child are enrolled in Study 26, both may be co-enrolled into the pharmacokinetic substudy with the adult serving as the control for the child. Preference will be given to a biologic parent of the same gender. If no eligible biologic parent is available for study, the next adult of the same gender and at the same TBTC site, who is substudy eligible, will serve as the adult control.

Exclusion Criteria

• None

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

US Department of Veterans Affairs

FED

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: lead

Responsible Party

Tuberculosis Trials Consortiu, DTBE, CDC

Principal Investigators

Marc Weiner, MD

Role: STUDY_CHAIR

VAMC and University of Texas Health Science Center San Antonio

Locations

Central Arkansas Veterans Health System

Little Rock, Arkansas, United States

University of Southern California Medical Center

Los Angeles, California, United States

University of California at San Diego

San Diego, California, United States

University of California, San Francisco

San Francisco, California, United States

Denver Public Health Department

Denver, Colorado, United States

Washington DC Veterans Administration Medical Center

Washington D.C., District of Columbia, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Northwestern University School of Medicine

Chicago, Illinois, United States

Hines Veterans Administration Medical Center

Hines, Illinois, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Boston University Medical Center

Boston, Massachusetts, United States

New Jersey School of Medicine

Newark, New Jersey, United States

Columbia University

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Veterans Administration Tennessee Valley Health Care System

Nashville, Tennessee, 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 VA Hospital

San Antonio, Texas, United States

Seattle-King County Health Department

Seattle, Washington, United States

Hopital Universitario Clementino Fraga Filho

Rio de Janeiro, Rio de Janeiro, Brazil

University of British Columbia

Vancouver, British Columbia, Canada

University of Manitoba

Winnepeg, Manitoba, Canada

Montreal Chest Institute

Montreal, Quebec, Canada

Agencia de Salut Publica

Barcelona, , Spain

Countries

United States; Brazil; Canada; Spain

Other Identifiers

CDC-NCHSTP-4679

Identifier Type: -

Identifier Source: org_study_id