HRZE Fasted/Fed in Newly Diagnosed TB

Overview

WHO recommends to take TB drugs while fasting: if TB drugs are taken with food, perhaps drug concentrations are too low; on the other hand: if this is not tolerated, drugs could also be taken with food. Do lower drug concentrations – with improved adherence to therapy – outweigh the disadvantage of lower drug blood concentrations over time? How exactly do the drug concentrations over time (pharmacokinetics) compare between fasting and fed conditions, especially in the early stage of TB treatment when patients are relatively sick, and relatively poorly tolerate TB drugs?

Full Title of Study: “The Influence of Fasting and Food on the Pharmacokinetics of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol in Newly Diagnosed TB Patients”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2014

Detailed Description

To evaluate the influence of concomitant food ingestion on the pharmacokinetics of HRZE in newly diagnosed TB patients To evaluate the influence of early disease on the PK parameters of HRZE in TB patients To compare the pharmacokinetics of HRZE in the early stage of disease with the pharmacokinetics of HRZE in more stable condition in newly diagnosed TB patients To evaluate adverse events of HRZE in TB patients

Interventions

  • Drug: intravenous administration of 1st line TB drugs, day 1
    • TB drugs IV on day 1 for calculation of bioavailability while fasting or fed

Arms, Groups and Cohorts

  • Active Comparator: Fasting-Fed
    • blood sampling on 3 consecutive days; by randomization, drug treatment as follows: day 1, HRZE as iv therapy; on day 2, HRZE as oral therapy in fasting condition (2 hours before meals); and on day 3 HRZE as oral therapy in fed condition (after meals).
  • Active Comparator: Fed-Fasting
    • blood sampling on 3 consecutive days; by randomization, drug treatment as follows: day 1, HRZE therapy as iv therapy; day 2, HRZE as oral therapy in fed condition, and on day 3, HRZE as oral therapy in fasting condition

Clinical Trial Outcome Measures

Primary Measures

  • pharmacokinetics
    • Time Frame: 3 days – week 1 and week 8
    • pharmacokinetics (AUC0-8, Cmax, and Tmax); comparison between TB patients who take HRZE concomitant with food and TB patients who take HRZE concomitant without food, weeks 1 and 8 of treatment
  • pharmacokinetics (AUC0-8, Cmax, and Tmax) of HRZE
    • Time Frame: 11 time points, 3 consecutive days – wk 1 & 8
    • PK curves from venous blood specimens sampled from indwelling venous catheter

Secondary Measures

  • To evaluate adverse events of HRZE, week 1 and 8 – while taking food or not
    • Time Frame: week 1 – week 8
    • tolerance – acceptance; vomiting, refusal

Participating in This Clinical Trial

Inclusion Criteria

  • Patients with TB who are starting with HRZE therapy – Age > 18 years old – Written informed consent Exclusion Criteria:

  • Use of antacids, which cannot be discontinued for study days – Active, unstable hepatic disease (with jaundice, HRZ)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Medical Center Groningen
  • Collaborator
    • University of Groningen
  • Provider of Information About this Clinical Study
    • Principal Investigator: Tjip van der Werf, Professor, Infectious Diseases & Tuberculosis – University Medical Center Groningen

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