NCT02121314

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?

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2013

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2013

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

January 25, 2014

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
22 days until next milestone

First Posted

Study publicly available on registry

April 23, 2014

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2014

Completed
Last Updated

April 8, 2015

Status Verified

April 1, 2015

Enrollment Period

9 months

First QC Date

January 25, 2014

Last Update Submit

April 7, 2015

Conditions

Tuberculosis

Keywords

TBbioavailabilityHRZEfastingfed

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (1)

  • To evaluate adverse events of HRZE, week 1 and 8 - while taking food or not

    week 1 - week 8

Other Outcomes (1)

  • confounding factors for primary and secondary outcomes

    weeks 1 and 8

Study Arms (2)

Fasting-Fed

ACTIVE COMPARATOR

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

Fed-Fasting

ACTIVE COMPARATOR

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

Interventions

intravenous administration of 1st line TB drugs, day 1DRUG

TB drugs IV on day 1 for calculation of bioavailability while fasting or fed

Fasting-FedFed-Fasting

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with TB who are starting with HRZE therapy
  • Age \> 18 years old
  • Written informed consent

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sardjito Central Hospital

Yogyakarta, Indonesia

Location

Related Publications (2)

  • Saktiawati AMI, Harkema M, Setyawan A, Subronto YW, Sumardi, Stienstra Y, Aarnoutse RE, Magis-Escurra C, Kosterink JGW, van der Werf TS, Alffenaar JC, Sturkenboom MGG. Optimal Sampling Strategies for Therapeutic Drug Monitoring of First-Line Tuberculosis Drugs in Patients with Tuberculosis. Clin Pharmacokinet. 2019 Nov;58(11):1445-1454. doi: 10.1007/s40262-019-00763-3.

    PMID: 30997650DERIVED

  • Saktiawati AM, Sturkenboom MG, Stienstra Y, Subronto YW, Sumardi, Kosterink JG, van der Werf TS, Alffenaar JW. Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment-naive TB patients: a randomized cross-over trial. J Antimicrob Chemother. 2016 Mar;71(3):703-10. doi: 10.1093/jac/dkv394. Epub 2015 Dec 11.

    PMID: 26661397DERIVED

MeSH Terms

Conditions

TuberculosisFastingLecithin Cholesterol Acyltransferase Deficiency

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsFeeding BehaviorBehaviorHypoalphalipoproteinemiasHypolipoproteinemiasLipid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Infectious Diseases & Tuberculosis

Study Record Dates

First Submitted

January 25, 2014

First Posted

April 23, 2014

Study Start

July 1, 2013

Primary Completion

April 1, 2014

Study Completion

June 1, 2014

Last Updated

April 8, 2015

Record last verified: 2015-04

Locations

ID(1)