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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: Isoniazid; Drug: Rifapentine

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

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Daily Isoniazid for 9 months; Participants received isoniazid daily for 9 months for treatment of latent tuberculosis infection.	Drug: Isoniazid; Isoniazid daily, oral, nine months; Other Names: INH
Experimental: weekly Rifapentine plus Isoniazid for 12 weeks; Participants received once-weekly rifapentine plus isoniazid for 12 weeks under direct observation for treatment of latent tuberculosis infection.	Drug: Rifapentine; Rifapentine plus Isoniazid taken orally, weekly, by direct observation for 12 weeks; Other Names: Priftin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rifapentine Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity, AUC0-inf	Rifapentine exposure was estimated in children and adults receiving once-weekly rifapentine plus isoniazid. A sparse sampling design used a plasma sample collected 24 hours after administration of study drugs.	24 hours after study-drug administration; AUC0-inf estimated using a nonlinear mixed-effects pharmacokinetic model incorporating the 24-hour rifapentine concentration, C24.
Correlation Between Rifapentine C24 and AUC0-inf	Value represents the coefficient of determination (R-squared) for the relationship between rifapentine C24 and AUC0-inf.	24 hours after study-drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rifapentine AUC0-inf by Tablet Administration Method in Children	Comparison of rifapentine AUC0-inf between participants receiving crushed and whole rifapentine tablets.	24 hours after study-drug administration

Collaborators and Investigators

• Sponsor: Centers for Disease Control and Prevention
• Collaborators: US Department of Veterans Affairs
• Investigators: Study Chair: Marc Weiner, MD, VAMC and University of Texas Health Science Center San Antonio

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: September 10, 2005
• First Submitted That Met QC Criteria: September 10, 2005
• First Posted (Estimated): September 14, 2005

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: children; pharmacokinetics; TB; tuberculosis
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Isoniazid; rifapentine
• Other Study ID Numbers: CDC-NCHHSTP-4679