TBTC Study 26 PK: Rifapentine Pharmacokinetics in Children During Treatment of Latent TB Infection - Full Text View

Sponsors and Collaborators:	Centers for Disease Control and Prevention Department of Veterans Affairs
Information provided by:	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00164450

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:	Treatment, Non-Randomized, Open Label, Dose Comparison, Parallel Assignment, Pharmacokinetics Study
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:

MedlinePlus related topics: Tuberculosis

Drug Information available for: Isoniazid Rifapentine Ftivazide

U.S. FDA Resources

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:

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.
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00164450

Show 24 Study Locations

Sponsors and Collaborators

Centers for Disease Control and Prevention

Department of Veterans Affairs

Investigators

Study Chair:

Marc Weiner, MD

VAMC and University of Texas Health Science Center San Antonio

More Information

No publications provided

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

Keywords provided by Centers for Disease Control and Prevention:

tuberculosis
TB
pharmacokinetics
children

Study placed in the following topic categories:

Antimetabolites
Bacterial Infections
Anti-Bacterial Agents
Gram-Positive Bacterial Infections
Antilipemic Agents

Rifapentine
Mycobacterium Infections
Tuberculosis
Antitubercular Agents
Isoniazid

Additional relevant MeSH terms:

Bacterial Infections
Antimetabolites
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Rifapentine
Actinomycetales Infections
Pharmacologic Actions
Antibiotics, Antitubercular

Anti-Bacterial Agents
Gram-Positive Bacterial Infections
Therapeutic Uses
Mycobacterium Infections
Tuberculosis
Antitubercular Agents
Fatty Acid Synthesis Inhibitors
Leprostatic Agents
Isoniazid

ClinicalTrials.gov processed this record on July 06, 2009