Clinical trial NCT01043575: High Dose Rifapentine Pharmacokinetics, Tolerability and Safety Dosage Rifapentine for Treatment of Tuberculosis
Official title: Pharmacokinetic and Pharmacodynamic Studies of Efficacy, Tolerability and Safety of Higher Dosage Rifapentine for Treatment of Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smear Positive, Pan-sensitive, Pulmonary Tuberculosis
Keywords: rifapentine, pharmacokinetics, pharmacodynamics, tuberculosis
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
First posted: 2010-01-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to characterize rifapentine drug levels in patients with TB in relationship to its effectiveness in treating TB and any adverse effects experienced by participants.

Detailed description: This is a one-period, non-blinded, multi-center pharmacokinetic substudy of rifapentine and rifampin in patients with tuberculosis enrolled in Tuberculosis Trials Consortium (TBTC) Study 29. This PK substudy will use a convenience sample, i.e. be restricted to TBTC sites having logistical capacity for intensive pharmacokinetic sampling. These sites will have non-random selection of patients. In addition to the intensive sampling of 60 patients in this PK study, all patients receiving rifapentine in Study 29 will be eligible for sparse PK sampling as part of the parent treatment protocol.

Eligibility criteria: Inclusion Criteria:

* Any patient enrolled in TBTC Study 29.
* Provision of informed consent for the study.
* Willingness to be sampled in an out-patient clinic or be admitted to a General Clinical Research Center (GCRC) or hospital on one occasion

Exclusion Criteria:

• Severe anemia as defined by a hematocrit less than 25% (most recent value, measured within 30 days of the PK study).

Primary outcomes:
measure: The primary objective of this study is to characterize rifapentine pharmacokinetic parameters (AUC0-24 and peak concentration) in patients with TB.
timeFrame: on or after the 10th day from the start of Study 29 therapy
Secondary outcomes:
measure: • To assess the pharmacodynamic effects of higher dose, daily rifapentine AUC0-24 on tolerability and safety during two months of treatment of tuberculosis.
timeFrame: on or after the 10th day of study therapy
measure: • To assess the pharmacodynamic effect of rifapentine pharmacokinetic parameters (AUC0-24) on biomarkers of treatment activity in patients with tuberculosis.
timeFrame: on or after the 10th day of study therapy
measure: • To assess in multivariate analyses the pharmacodynamic effect on biomarkers of treatment activity of the independent variables of rifapentine AUC0-24, HIV infection, isoniazid exposure (AUC0-12) and study site (African vs. non-African).
timeFrame: on or after the 10th day of study therapy
measure: To determine if free (non-protein bound) rifapentine and free rifampin exposures are directly associated with anti-mycobacterial activity.
timeFrame: on or after the 10th day of study therapy
measure: • To determine the effects of polymorphisms of transporter genes on rifampin and rifapentine pharmacokinetic parameters.
timeFrame: on or after the 10th day of therapy
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Public Health
state: Colorado
city: Denton
country: United States
facility: University of North Texas
state: Texas
city: Harlingen
country: United States
facility: TBTC site 40 / South Texas
state: Texas
city: San Antonio
country: United States
facility: Audie L. Murphy VA Medical Center
state: Texas
city: Durban
country: South Africa
facility: University of KwaZulu Natal
city: Kampala
country: Uganda
facility: Uganda / Case Western Reserve Research Collaboration
Study officials:
affiliation: University of Texas Health Sciences Campus, San Antonio
name: Marc Weiner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gewitz AD, Solans BP, Mac Kenzie WR, Heilig C, Whitworth WC, Johnson JL, Nsubuga P, Dorman S, Weiner M, Savic RM; Tuberculosis Trials Consortium of the Centers for Disease Control and Prevention. Longitudinal Model-Based Biomarker Analysis of Exposure-Response Relationships in Adults with Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0179420. doi: 10.1128/AAC.01794-20. Epub 2021 Jul 12.
citation: Weiner M, Gelfond J, Johnson-Pais TL, Engle M, Johnson JL, Whitworth WC, Bliven-Sizemore E, Nsubuga P, Dorman SE, Savic R; Pharmacokinetics/Pharmacodynamics Group of Tuberculosis Trials Consortium. Decreased plasma rifapentine concentrations associated with AADAC single nucleotide polymorphism in adults with tuberculosis. J Antimicrob Chemother. 2021 Feb 11;76(3):582-586. doi: 10.1093/jac/dkaa490.