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

Tuberculosis Clinical Trial

Official title:

TBTC Study 26 PK: Rifapentine Pharmacokinetics in Children Receiving Once Weekly Rifapentine and Isoniazid for the Treatment of Latent Tuberculosis Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00164450
• Other study ID #: CDC-NCHSTP-4679
• Status: Completed
• Phase: N/A
• First received: September 10, 2005
• Last updated: August 22, 2008
• Start date: September 2005
• Est. completion date: August 2008

Study information

• Verified date: August 2008
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

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:

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• Rifapentine + isoniazid once weekly for 3 months

Locations

Country	Name	City	State
Brazil	Hopital Universitario Clementino Fraga Filho	Rio de Janeiro
Canada	Montreal Chest Institute	Montreal	Quebec
Canada	University of British Columbia	Vancouver	British Columbia
Canada	University of Manitoba	Winnepeg	Manitoba
Spain	Agencia de Salut Publica	Barcelona
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Boston University Medical Center	Boston	Massachusetts
United States	Northwestern University School of Medicine	Chicago	Illinois
United States	Denver Public Health Department	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	University of North Texas Health Science Center	Fort Worth	Texas
United States	Hines Veterans Administration Medical Center	Hines	Illinois
United States	Houston Veterans Administration Medical Center	Houston	Texas
United States	Central Arkansas Veterans Health System	Little Rock	Arkansas
United States	University of Southern California Medical Center	Los Angeles	California
United States	Veterans Administration Tennessee Valley Health Care System	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	New Jersey School of Medicine	Newark	New Jersey
United States	Audie L. Murphy VA Hospital	San Antonio	Texas
United States	University of California at San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	Seattle-King County Health Department	Seattle	Washington
United States	Washington DC Veterans Administration Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	VA Office of Research and Development

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine whether rifapentine exposure (level 24 hours after drug ingestion) is equivalent in young children receiving weight-based dosing to adults receiving 900 mg.		24 hours after drug ingestion	No
Secondary	Correlate estimated rifapentine exposure with toxicity in young children receiving rifapentine and isoniazid for latent tuberculosis infection.		During the three months of taking rifapentine	Yes
Secondary	Validate the accuracy of estimated rifapentine exposure with pediatric rifapentine dose based on weight.		24 hours after drug ingestion	No
Secondary	Determine estimated drug bioavailability in pediatric subjects (ages 2 to < 12 years) given higher mg/kg doses of rifapentine.		24 hours after drug ingestion	No
Secondary	Determine the association in adults between polymorphisms of MDR1 genotype (P-glycoprotein) and rifapentine estimated exposure.		at the time of blood draw	No
Secondary	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.		at the time of blood draw	No