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NCT Number: NCT02563327

Pharmacokinetic and Pharmacodynamic Study of High-Dose Rifapentine and Moxifloxacin for Treatment of Tuberculosis

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.

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Key information

Conditions

Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Mycobacterium Infections

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Joint Clinical Research Centre/ Makerere Univ Med Sch, Kampala, Uganda

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

rifapentine

Drug

A rifamycin with activity against Mycobacterium tuberculosis

Other names: Priftin

moxifloxacin

Drug

A fluoroquinolone

Rifampin

Drug

A rifamycin with activity against Mycobacterium tuberculosis

Isoniazid

Drug

An anti-tuberculosis agent

Pyrazinamide

Drug

An anti-tuberculosis agent

Ethambutol

Drug

An anti-tuberculosis agent

pyridoxine

Dietary Supplement

An essential vitamin

Other names: Vitamin B6

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

Sponsors and collaborators

Lead sponsor

Centers for Disease Control and Prevention

Fed

Collaborators

  • Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Registry information

Official study title

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

Acronym: S31PK/PD

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Sep 30, 2015
Registry last updated
Aug 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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