Pharmacokinetic Issues of Moxifloxacin Plus Rifapentine

December 5, 2017 updated by: Johns Hopkins University

Pharmacokinetic Issues in the Use of Moxifloxacin Plus Rifapentine

The purpose of this study is to determine the pharmacokinetics (how a drug is absorbed, distributed, and eliminated by the body) of moxifloxacin alone versus moxifloxacin given with rifapentine. Researchers believe that understanding how these tuberculosis drugs interact when given together may help to determine the best drug treatment plan for use in future studies. Volunteers will take moxifloxacin daily by mouth for the first part of the study and then moxifloxacin in combination with rifapentine during the second part of the study. Sixteen healthy men and women will be recruited from Johns Hopkins University School of Medicine to volunteer for this study. They will be required to stay in the inpatient unit twice, each time for 84 hours. Study procedures will include having a tube placed in a vein to draw several blood samples over time. Volunteers will participate in the study for a maximum of 48 days, including screening and follow-up visits.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

New drugs are urgently needed to shorten the duration of tuberculosis (TB) treatment and to facilitate the delivery of directly observed therapy. Preliminary data indicates that a TB treatment regimen that includes moxifloxacin plus rifapentine may have excellent antituberculosis activity that could allow for shortening of total TB treatment duration. However, little is known about possible pharmacokinetic interactions between the two drugs in humans. More specifically, moxifloxacin is metabolized via glucuronide and sulfate conjugation to inactive metabolites. Given that rifapentine induces the activity of phase II enzymes including glucuronosyltransferase and sulphotransferase, it is possible that rifapentine may alter the pharmacokinetics of moxifloxacin. This study will be a prospective, phase I, single center pharmacokinetic study in healthy subjects. The trial will compare the pharmacokinetics of moxifloxacin alone versus moxifloxacin administered with thrice-weekly rifapentine, each administered orally. There will be two parts to the trial: Part I (Days 1-4) during which moxifloxacin is administered alone; and Part II (Days 5-19) during which moxifloxacin is co-administered with thrice-weekly rifapentine. A 24-hour pharmacokinetic profile of moxifloxacin will be obtained following dose administration of moxifloxacin on Day 4 to obtain baseline steady state data at a dose of 400 mg daily. On Day 5, rifapentine will be added to the regimen at a dose of 900 mg thrice weekly, and a 48-hour pharmacokinetic profile for rifapentine and its metabolite, 25-desacetyl-rifapentine will be obtained after the first dose. On Day 19, 72-hour pharmacokinetic profiles for moxifloxacin, rifapentine, and 25-desacetyl-rifapentine will be performed. Safety and tolerability assessments will be performed at designated intervals throughout the study. Beginning on Day 1, subjects will receive moxifloxacin 400 mg daily for 19 days (Days 1-19). Beginning on Day 5, subjects will also receive rifapentine 900 mg thrice weekly (to be administered on Days 5, 7, 9, 12, 14, 16 and 19). Study participants will be 16 healthy adults, ages 18-65, recruited through Johns Hopkins University School of Medicine. The primary study objectives are to: compare, in healthy volunteers, the pharmacokinetics of moxifloxacin alone versus moxifloxacin co-administered with thrice-weekly rifapentine and describe the safety and tolerability of moxifloxacin co-administered with rifapentine. The secondary study objective is to evaluate for rifapentine autoinduction of metabolism in healthy volunteers receiving thrice-weekly rifapentine. The primary safety outcome will be the proportion of subjects with any Grade 3 or 4 toxicity associated with study medications or any serious adverse event. The secondary safety outcomes will be the proportion of subjects with any Grade 1 or 2 toxicity associated with study medications, and the proportion of subjects discontinuing study medications for any reason.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

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

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ability and willingness to provide written informed consent.
  • Age greater than or equal to 18 years, and less than or equal to 65 years.
  • Within 14 or fewer days prior to enrollment, a complete blood count, comprehensive serum chemistry profile, and HIV antibody test will be performed, with the following laboratory values:
  • Serum amino aspartate transferase (AST) at or within the normal limits for the laboratory
  • Total bilirubin level at, below, or within the normal limits for the laboratory
  • Creatinine level at, below, or within the normal limits for the laboratory
  • Uric acid at, below, or within the normal limits for the laboratory
  • Hemoglobin greater than 12.0 for men, greater than 11.0 for women
  • Platelet count greater than or equal to 125,000/cu mm
  • Absolute neutrophil count greater than or equal to 1250/cu mm
  • Potassium level of at least 3.5 mEq/L
  • Serum albumin at or within normal limits for the laboratory
  • HIV antibody test negative
  • For women of childbearing potential, a negative serum beta-Human Chorionic Gonadatropin (bHCG) pregnancy test, performed at screening and on Day 0.
  • During the study and for 14 days after the last dose of study medication, women of childbearing potential must agree to practice a double-barrier method of birth control (e.g., condom plus spermicidal foam, condom plus diaphragm, etc) or to abstain from heterosexual vaginal intercourse since hormonal contraceptives will be prohibited during the study. Female subjects must plan on not getting pregnant during the study and for 14 days after the last dose of study medication.
  • Access to a telephone for the duration of the study.
  • Within 14 days or fewer prior to enrollment, an electrocardiogram with corrected QT interval (QTc) less than or equal to 0.44 seconds.

Exclusion Criteria:

  • Breastfeeding
  • Known intolerance to either of the study drugs or to fluoroquinolone antibiotics
  • Use of rifamycin or fluoroquinolone antibiotics in the 30 days prior to enrollment
  • Inability to take oral medications
  • History of any renal, hepatic, cardiac (except benign heart murmur), or endocrine disorder; or malignancy; or immunocompromised
  • History of any acute or chronic illness that requires current medical therapy
  • Prior gastrointestinal surgery involving stomach, biliary system, pancreas, or small intestine
  • Any medical condition that, in the opinion of the investigator, would interfere with the subject's ability to participate in the protocol
  • Any illicit drug use within the preceding 2 months. Subjects must agree to abstain from alcohol, tobacco, and illicit drug use during the study
  • Current use of any prescription medication(s)
  • Planned use, during the study from Day 0 through the last PK blood draw, of any of the following: prescription medication(s), herbal supplement(s), vitamin(s), mineral supplement(s), or over-the-counter medication(s) with the exception of acetaminophen
  • History of prolonged QT syndrome
  • Participation in any other investigational drug study within 21 days prior to study entry and during the study
  • Inability to participate in pharmacokinetic visits

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Moxifloxacin and Rifapentine
Drug: Moxifloxacin
Drug: Rifapentine

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2007

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 24, 2008

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 24, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 12, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2007

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 16, 2007

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 7, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NA_00007322

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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