Pharmacokinetic and Pharmacodynamic Study of High-Dose Rifapentine and Moxifloxacin for Treatment of Tuberculosis (S31PK/PD)

August 5, 2026 updated by: Centers for Disease Control and Prevention

TBTC Study 31 PK/PD: Population Pharmacokinetic and Pharmacodynamic Study of Efficacy and Safety of High-Dose Rifapentine and Moxifloxacin for Treatment of Tuberculosis in the Study 31 Treatment Trial: Intensive PK Sampling

The Tuberculosis Trials Consortium (TBTC) Study 31 is a phase 3 trial evaluating rifapentine-containing regimens for treatment-shortening of drug-susceptible pulmonary tuberculosis. This pharmacokinetic/pharmacodynamic (PK/PD) substudy evaluates rifapentine and moxifloxacin exposure-response relationships for efficacy and safety outcomes. Intensive and sparse PK sampling are performed among participants receiving rifapentine-containing regimens. PK and clinical outcomes data are used to characterize population pharmacokinetics and assess relationships between drug exposure, culture conversion, treatment failure or relapse, and adverse events.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This pharmacokinetic/pharmacodynamic (PK/PD) substudy is conducted within TBTC Study 31, a phase 3 randomized trial evaluating rifapentine-containing regimens for treatment-shortening of drug-susceptible pulmonary tuberculosis.

The substudy evaluates population pharmacokinetics and exposure-response relationships for rifapentine and moxifloxacin administered in rifapentine-containing multidrug regimens. Rifapentine is administered at a daily dose of 1200 mg with food, with or without moxifloxacin.

Participants undergo intensive and sparse pharmacokinetic sampling between Weeks 2 and 8 of treatment. Intensive PK sampling includes serial plasma collections over approximately 24 hours in a subset of participants, with additional later sampling performed after at least 14 days. Sparse PK sampling is performed in the remaining Study 31 participants.

Population PK models are developed using nonlinear mixed-effects methods to estimate individual exposure parameters including area under the concentration-time curve (AUC0-24) and maximum concentration (Cmax). PK/PD analyses evaluate relationships between drug exposure and efficacy outcomes, including culture conversion and treatment failure or relapse, as well as safety outcomes including grade 3 or higher adverse events.

The study also evaluates the effect of covariates including demographic and clinical factors on rifapentine and moxifloxacin pharmacokinetics.

Study Type

Interventional

Enrollment (Actual)

2516

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Uganda
      • Kampala, Uganda
        • Joint Clinical Research Centre/ Makerere Univ Med Sch
  • United States
    • Texas
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at
  • Vietnam
      • Hanoi, Vietnam
        • National TB Program

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 years or greater
  • Enrolled in TBTC Study 31
  • Randomized to receive one of the rifapentine treatment regimens.
  • Willingness to be sampled 6 times during 1 PK sampling session and 2 - 3 times during another PK sampling session at an outpatient clinic, a clinical research center, or a hospital.
  • Written informed consent given for the Study 31 PK/PD study

Exclusion Criteria:

  • Hematocrit < 25% most recent value, measured within 30 days before PK/PD study enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard Therapy

Eight weeks of daily treatment with rifampin, isoniazid, pyrazinamide, and ethambutol, followed by Eighteen weeks of daily treatment with rifampin and isoniazid. All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose.

Study drug doses: rifampin, 600 mg; isoniazid, 300 mg; pyrazinamide, < 55kg 1000 mg, >= 55-75 kg 1500 mg, >75 kg 2000 mg; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg.
Drug: Rifampin
A rifamycin with activity against Mycobacterium tuberculosis
Drug: Isoniazid
An anti-tuberculosis agent
Drug: Pyrazinamide
An anti-tuberculosis agent
Drug: Ethambutol
An anti-tuberculosis agent
Dietary supplement: Pyridoxine
An essential vitamin
Other Names:
  • Vitamin B6
Experimental: Rifapentine-containing Regimen

Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and ethambutol, followed by Nine weeks of daily treatment with rifapentine and isoniazid. All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose.

Study drug doses: rifapentine 1200 mg; isoniazid, 300 mg; pyrazinamide, < 55kg 1000 mg, >= 55-75 kg 1500 mg, >75 kg 2000 mg; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg.
Drug: Isoniazid
An anti-tuberculosis agent
Drug: Pyrazinamide
An anti-tuberculosis agent
Drug: Ethambutol
An anti-tuberculosis agent
Dietary supplement: Pyridoxine
An essential vitamin
Other Names:
  • Vitamin B6
Drug: Rifapentine
A rifamycin with activity against Mycobacterium tuberculosis
Other Names:
  • Priftin
Experimental: Rifapentine- and Moxifloxacin-containing Regimen

Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and moxifloxacin, followed by Nine weeks of daily treatment with rifapentine, isoniazid, and moxifloxacin. All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose.

Study drug doses: rifapentine 1200 mg; isoniazid, 300 mg; pyrazinamide, < 55kg 1000 mg, >= 55-75 kg 1500 mg, >75 kg 2000 mg; moxifloxacin, 400 mg.
Drug: Isoniazid
An anti-tuberculosis agent
Drug: Pyrazinamide
An anti-tuberculosis agent
Dietary supplement: Pyridoxine
An essential vitamin
Other Names:
  • Vitamin B6
Drug: Rifapentine
A rifamycin with activity against Mycobacterium tuberculosis
Other Names:
  • Priftin
Drug: Moxifloxacin
A fluoroquinolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rifapentine Area Under the Concentration-Time Curve From 0 to 24 Hours (AUC0-24)
Time Frame: Plasma concentrations measured at approximately 0.5, 3, 5, 9, 12, and 24 hours after the pharmacokinetic reference dose during Weeks 2-8 after treatment initiation.
To characterize rifapentine exposure (AUC0-24) using population pharmacokinetics.
Plasma concentrations measured at approximately 0.5, 3, 5, 9, 12, and 24 hours after the pharmacokinetic reference dose during Weeks 2-8 after treatment initiation.
Rifapentine Maximum Plasma Concentration (Cmax)
Time Frame: Plasma concentrations measured during 0-24 hours following the pharmacokinetic reference dose; PK sampling performed during Weeks 2-8 after treatment initiation.
To characterize rifapentine peak concentration using population pharmacokinetic modeling.
Plasma concentrations measured during 0-24 hours following the pharmacokinetic reference dose; PK sampling performed during Weeks 2-8 after treatment initiation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With TB-Related Unfavorable Outcomes in the Rifapentine-Moxifloxacin Regimen
Time Frame: Efficacy assessed through 12 months after treatment initiation; pharmacokinetics assessed during Weeks 2-8.
Number of microbiologically eligible participants with TB-related unfavorable outcomes in the rifapentine-moxifloxacin regimen through 12 months after treatment initiation. Associations with rifapentine and moxifloxacin exposures are reported in separate Statistical Analyses.
Efficacy assessed through 12 months after treatment initiation; pharmacokinetics assessed during Weeks 2-8.
Number of Participants With Grade 3 or Higher Adverse Events
Time Frame: Pharmacokinetics assessed Weeks 2-8; Safety assessed from randomization through treatment period, up to 14 days after last dose.
Number of participants with grade 3 or higher adverse events during the treatment period in each rifapentine-containing treatment arm. Associations with rifapentine and moxifloxacin exposures are reported in separate Statistical Analyses.
Pharmacokinetics assessed Weeks 2-8; Safety assessed from randomization through treatment period, up to 14 days after last dose.
Moxifloxacin Area Under the Concentration-Time Curve at Steady State
Time Frame: Weeks 2 through 8 after treatment initiation.
To characterize moxifloxacin pharmacokinetics when moxifloxacin was administered 400 mg daily with rifapentine 1200 mg daily.
Weeks 2 through 8 after treatment initiation.
Number of Participants With Grade 3 or Higher Adverse Events in the Rifapentine-Moxifloxacin Regimen
Time Frame: Pharmacokinetics assessed Weeks 2-8; Safety assessed from randomization through treatment period, up to 14 days after last dose.
Number of participants with grade 3 or higher adverse events in the rifapentine-moxifloxacin regimen during the treatment period. The association between moxifloxacin exposure and safety outcomes was evaluated using multivariable logistic regression and is reported in the Statistical Analysis section.
Pharmacokinetics assessed Weeks 2-8; Safety assessed from randomization through treatment period, up to 14 days after last dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centers for Disease Control and Prevention

Collaborators

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Investigators

  • Study Chair: Rada Savic, PhD, University of San Francisco School of Pharmacy, San Francisco, CA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 25, 2016

Primary Completion (Actual)

August 30, 2021

Study Completion (Actual)

August 30, 2021

Study Registration Dates

First Submitted

September 15, 2015

First Submitted That Met QC Criteria

September 29, 2015

First Posted (Estimated)

September 30, 2015

Study Record Updates

Last Update Posted (Actual)

August 27, 2026

Last Update Submitted That Met QC Criteria

August 5, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDC-NCHHSTP-6719

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified participant data underlying published results may be made available through an approved data sharing platform following publication and sponsor approval.

IPD Sharing Time Frame

Following publication.

IPD Sharing Access Criteria

Access may be provided to qualified researchers upon request and approval by the study sponsor and data access committee.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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