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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pharmacokinetic and Pharmacodynamic Studies of Efficacy, Tolerability and Safety of Higher Dosage Rifapentine for Treatment of Tuberculosis

Conditions
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Smear Positive, Pan-sensitive, Pulmonary Tuberculosis

Intervention / Treatment
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* Drug: Rifapentine
* Drug: Rifampin


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Rifapentine | Drug: Rifapentine<br>* During the first 8 weeks of therapy for TB participants > 45 kg will receive rifapentine 600 mg orally given 5 per week and for participants < 45 kg participants will receive 450 mg orally given 5 days per week<br>* Other names: Priftin;|
| Active Comparator: 2<br>Rifampin | Drug: Rifampin<br>* During the first 8 weeks of therapy participants will receive rifampin at standard doses (e.g. 600 mg) 5 days per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rifapentine, pharmacokinetics, pharmacodynamics, tuberculosis