HRZE Fasted/Fed in Newly Diagnosed TB

Study Overview
=================
Brief Summary
-----------------
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?

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

Official Title
-----------------
The Influence of Fasting and Food on the Pharmacokinetics of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol in Newly Diagnosed TB Patients

Conditions
-----------------
Tuberculosis

Intervention / Treatment
-----------------
* Drug: intravenous administration of 1st line TB drugs, day 1


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fasting-Fed<br>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). | Drug: intravenous administration of 1st line TB drugs, day 1<br>* TB drugs IV on day 1 for calculation of bioavailability while fasting or fed<br>|
| Active Comparator: Fed-Fasting<br>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 | Drug: intravenous administration of 1st line TB drugs, day 1<br>* TB drugs IV on day 1 for calculation of bioavailability while fasting or fed<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics | 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 | 3 days - week 1 and week 8 | 
| pharmacokinetics (AUC0-8, Cmax, and Tmax) of HRZE | PK curves from venous blood specimens sampled from indwelling venous catheter | 11 time points, 3 consecutive days - wk 1 & 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate adverse events of HRZE, week 1 and 8 - while taking food or not | tolerance - acceptance; vomiting, refusal | week 1 - week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TB, fed, bioavailability, HRZE, fasting