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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00164450
First received: September 10, 2005
Last updated: August 22, 2008
Last verified: August 2008
  Purpose

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.


Condition Intervention
Tuberculosis
Drug: Rifapentine + isoniazid once weekly for 3 months

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: TBTC Study 26 PK: Rifapentine Pharmacokinetics in Children Receiving Once Weekly Rifapentine and Isoniazid for the Treatment of Latent Tuberculosis Infection

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Determine whether rifapentine exposure (level 24 hours after drug ingestion) is equivalent in young children receiving weight-based dosing to adults receiving 900 mg. [ Time Frame: 24 hours after drug ingestion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlate estimated rifapentine exposure with toxicity in young children receiving rifapentine and isoniazid for latent tuberculosis infection. [ Time Frame: During the three months of taking rifapentine ] [ Designated as safety issue: Yes ]
  • Validate the accuracy of estimated rifapentine exposure with pediatric rifapentine dose based on weight. [ Time Frame: 24 hours after drug ingestion ] [ Designated as safety issue: No ]
  • Determine estimated drug bioavailability in pediatric subjects (ages 2 to < 12 years) given higher mg/kg doses of rifapentine. [ Time Frame: 24 hours after drug ingestion ] [ Designated as safety issue: No ]
  • Determine the association in adults between polymorphisms of MDR1 genotype (P-glycoprotein) and rifapentine estimated exposure. [ Time Frame: at the time of blood draw ] [ Designated as safety issue: No ]
  • Determine the frequency of lower antitubercular drug concentrations in adults with acetylator status determined by N-acetyltransferase genotypes and of rifapentine by C24 and by MDR1 genotypes. [ Time Frame: at the time of blood draw ] [ Designated as safety issue: No ]

Estimated Enrollment: 230
Study Start Date: September 2005
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
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
  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00164450

  Hide Study Locations
Locations
United States, Arkansas
Central Arkansas Veterans Health System
Little Rock, Arkansas, United States, 72205
United States, California
University of Southern California Medical Center
Los Angeles, California, United States, 90033
University of California at San Diego
San Diego, California, United States, 92103
University of California, San Francisco
San Francisco, California, United States, 94110
United States, Colorado
Denver Public Health Department
Denver, Colorado, United States, 80204
United States, District of Columbia
Washington DC Veterans Administration Medical Center
Washington, District of Columbia, United States, 20422
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30303
United States, Illinois
Northwestern University School of Medicine
Chicago, Illinois, United States, 21231
Hines Veterans Administration Medical Center
Hines, Illinois, United States, 60141
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
United States, New Jersey
New Jersey School of Medicine
Newark, New Jersey, United States, 07103
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Tennessee
Veterans Administration Tennessee Valley Health Care System
Nashville, Tennessee, United States, 37232
United States, Texas
University of North Texas Health Science Center
Fort Worth, Texas, United States, 76104
Houston Veterans Administration Medical Center
Houston, Texas, United States, 77030
Audie L. Murphy VA Hospital
San Antonio, Texas, United States, 78284
United States, Washington
Seattle-King County Health Department
Seattle, Washington, United States, 98104
Brazil
Hopital Universitario Clementino Fraga Filho
Rio de Janeiro, Brazil, 2194.590
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V5Z 4R4
Canada, Manitoba
University of Manitoba
Winnepeg, Manitoba, Canada, R3A 1R8
Canada, Quebec
Montreal Chest Institute
Montreal, Quebec, Canada, H2X 2P4
Spain
Agencia de Salut Publica
Barcelona, Spain, 080023
Sponsors and Collaborators
Investigators
Study Chair: Marc Weiner, MD VAMC and University of Texas Health Science Center San Antonio
  More Information

No publications provided

Responsible Party: William R. Mac Kenzie, MD, Medical Officer, Tuberculosis Trials Consortiu, DTBE, CDC
ClinicalTrials.gov Identifier: NCT00164450     History of Changes
Other Study ID Numbers: CDC-NCHSTP-4679
Study First Received: September 10, 2005
Last Updated: August 22, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Centers for Disease Control and Prevention:
tuberculosis
TB
pharmacokinetics
children

Additional relevant MeSH terms:
Latent Tuberculosis
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Isoniazid
Rifapentine
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antitubercular
Antimetabolites
Antitubercular Agents
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Leprostatic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014