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

Further Study Details: 

Primary Outcomes: • Determine whether rifapentine exposure is equivalent in young children receiving weight-based dosing to adults receiving 900 mg.
Secondary Outcomes: • Correlate estimated rifapentine exposure with toxicity in young children receiving rifapentine and isoniazid for latent tuberculosis infection.; • Validate the accuracy of estimated rifapentine exposure with pediatric rifapentine dose based on weight.; • Determine estimated drug bioavailability in pediatric subjects (ages 2 to < 12 years) given higher mg/kg doses of rifapentine.; • Determine the association in adults between polymorphisms of MDR1 genotype (P-glycoprotein) and rifapentine estimated exposure.; • 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.
Expected Total Enrollment:  230

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:

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

Ages Eligible for Study:  2 Years and above,  Genders Eligible for Study:  Both

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

Please refer to this study by ClinicalTrials.gov identifier  NCT00164450

TB Trials Consortium, Division of TB Elimination, CDC      404 639-8123    tbtc@cdc.gov

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

Study chairs or principal investigators

Marc Weiner, MD,  Study Chair,  VAMC and University of Texas Health Science Center San Antonio   

Study ID Numbers:  CDC-NCHSTP-4679
Last Updated:  September 13, 2005
Record first received:  September 10, 2005
ClinicalTrials.gov Identifier:  NCT00164450
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-20