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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

September 10, 2005
August 22, 2008
September 2005
August 2008   (final data collection date for primary outcome measure)
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 ]
• Determine whether rifapentine exposure is equivalent in young children receiving weight-based dosing to adults receiving 900 mg.
Complete list of historical versions of study NCT00164450 on ClinicalTrials.gov Archive Site
  • 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 ]
  • • 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.
Not Provided
Not Provided
 
TBTC Study 26 PK: Rifapentine Pharmacokinetics in Children During Treatment of Latent TB Infection
TBTC Study 26 PK: Rifapentine Pharmacokinetics in Children Receiving Once Weekly Rifapentine and Isoniazid for the Treatment of Latent Tuberculosis Infection

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.

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
Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Tuberculosis
Drug: Rifapentine + isoniazid once weekly for 3 months
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
230
August 2008
August 2008   (final data collection date for primary outcome measure)

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
Both
2 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Brazil,   Canada,   Spain
 
NCT00164450
CDC-NCHSTP-4679
Yes
William R. Mac Kenzie, MD, Medical Officer, Tuberculosis Trials Consortiu, DTBE, CDC
Centers for Disease Control and Prevention
Department of Veterans Affairs
Study Chair: Marc Weiner, MD VAMC and University of Texas Health Science Center San Antonio
Centers for Disease Control and Prevention
August 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP