High Dose Rifapentine Pharmacokinetics, Tolerability and Safety Dosage Rifapentine for Treatment of Tuberculosis

Phase 2

Completed

• Conditions: Smear Positive, Pan-sensitive, Pulmonary Tuberculosis
• Interventions: Drug: Rifapentine; Drug: Rifampin

• Registration Number: NCT01043575
• Lead Sponsor: Centers for Disease Control and Prevention

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.

Study Timeline

• Study Start: 2009-04
• Study First Submitted: 2010-01-06
• Study First Submitted QC: 2010-01-06
• Study First Posted: 2010-01-07
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Status Verified: 2012-08
• Last Update Submitted: 2012-08-15
• Last Update Posted: 2012-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Rifapentine	Rifapentine
2	Rifampin	Rifampin

Primary Outcome Measures

Name	Time	Method
The primary objective of this study is to characterize rifapentine pharmacokinetic parameters (AUC0-24 and peak concentration) in patients with TB.	on or after the 10th day from the start of Study 29 therapy

Secondary Outcome Measures

Name	Time	Method
• To assess the pharmacodynamic effects of higher dose, daily rifapentine AUC0-24 on tolerability and safety during two months of treatment of tuberculosis.	on or after the 10th day of study therapy
• To assess the pharmacodynamic effect of rifapentine pharmacokinetic parameters (AUC0-24) on biomarkers of treatment activity in patients with tuberculosis.	on or after the 10th day of study therapy
• 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).	on or after the 10th day of study therapy
To determine if free (non-protein bound) rifapentine and free rifampin exposures are directly associated with anti-mycobacterial activity.	on or after the 10th day of study therapy
• To determine the effects of polymorphisms of transporter genes on rifampin and rifapentine pharmacokinetic parameters.	on or after the 10th day of therapy

Trial Locations

Locations (6)

Uganda / Case Western Reserve Research Collaboration; 🇺🇬 Kampala, Uganda

Audie L. Murphy VA Medical Center; 🇺🇸 San Antonio, Texas, United States

Denver Public Health; 🇺🇸 Denver, Colorado, United States

TBTC site 40 / South Texas; 🇺🇸 Harlingen, Texas, United States

University of North Texas; 🇺🇸 Denton, Texas, United States

University of KwaZulu Natal; 🇿🇦 Durban, South Africa