Whole Blood Bactericidal Activity Against Mycobacterium Tuberculosis of Pyrazinamide Plus Allopurinol in Healthy Volunteers

April 12, 2017 updated by: National University Hospital, Singapore

Evaluating Pharmacokinetics and Whole Blood Bactericidal Activity Against Mycobacterium Tuberculosis of Pyrazinamide Boosted With Allopurinol in Healthy Volunteers

The purpose of this study is to evaluate the bactericidal activity against Mycobacterium tuberculosis of pyrazinamide in combination with allopurinol. Pharmacokinetics (PK) and whole blood bactericidal activity (WBA) will be measured in healthy volunteers following administration of pyrazinamide alone and in combination with allopurinol.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The whole blood bactericidal activity (WBA) assay is an ex vivo model for measuring the combined effects of administered drugs, host factors and strain factors on mycobacterial sterilisation. If performed in parallel with PK measurements, the method can be used to evaluate the effect of drugs throughout the dosing cycle. The aim of this trial is to assess the WBA activity and PK data of pyrazinamide and its metabolites boosted with allopurinol in healthy volunteers.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • 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

  • Singapore
      • Singapore, Singapore
        • National University Hospital, Singapore

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

Ages Eligible for Study

21 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Aged between 21 and 70 years old
  2. Male or female willing to comply with the study visits and procedures
  3. Willing and able to provide written informed consent

Exclusion Criteria:

  1. Women who are currently pregnant or breastfeeding
  2. Body weight 50kg or below
  3. HLA-B*5801 allele positive
  4. Clinical evidence (symptoms and/or signs) suggestive of active TB
  5. Previous hypersensitivity, intolerance or allergy to pyrazinamide or allopurinol
  6. Current use of any drugs or medication known to have an interaction with pyrazinamide or allopurinol, or known to have anti-TB activity
  7. Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations
  8. Known hepatic disease (including chronic hepatitis), recent hepatitis (within last 6 months) or alcohol abuse
  9. Known hyperuricaemia or evidence of hyperuricaemia at screening
  10. History or current episode of gout
  11. Any other significant condition that would, in the opinion of the investigator, compromise the volunteer's safety or outcome in the trial
  12. Current participation in other clinical intervention trial or research protocol

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low dose pyrazinamide
Day 0: Pyrazinamide 10mg/kg, Day 5: Allopurinol 100mg single dose, Day 6: Allopurinol 100mg single dose, Day 7: Pyrazinamide 10mg/kg plus allopurinol 100mg single dose, Day 8: Allopurinol 100mg single dose.
Drug: Allopurinol
Drug: Pyrazinamide
Experimental: Standard dose pyrazinamide
Day 0: Pyrazinamide 25mg/kg single dose, Day 5: Allopurinol 100mg single dose, Day 6: Allopurinol 100mg single dose, Day 7: Pyrazinamide 25mg/kg plus allopurinol 100mg single dose, Day 8: Allopurinol 100mg single dose.
Drug: Allopurinol
Drug: Pyrazinamide
Experimental: High dose pyrazinamide
Day 0: Pyrazinamide 35mg/kg single dose, Day 5: Allopurinol 100mg single dose, Day 6: Allopurinol 100mg single dose, Day 7: Pyrazinamide 35mg/kg plus allopurinol 100mg single dose, Day 8: Allopurinol 100mg single dose.
Drug: Allopurinol
Drug: Pyrazinamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative whole blood bactericidal activity (WBA)
Time Frame: 48 hours
Cumulative bactericidal activity calculated as log change CFU.day
48 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Plasma concentrations of study drugs to determine the Area Under the Curve (AUC)
Time Frame: 48 hours
48 hours
Plasma concentrations of study drugs to determine the Maximum Plasma Concentration (Cmax)
Time Frame: 48 hours
48 hours
Plasma concentrations of study drugs to determine the drug half-life (t1/2)
Time Frame: 48 hours
48 hours

Collaborators and Investigators

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

Sponsor

National University Hospital, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

February 1, 2016

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

February 24, 2016

First Submitted That Met QC Criteria

March 1, 2016

First Posted (Estimate)

March 7, 2016

Study Record Updates

Last Update Posted (Actual)

April 13, 2017

Last Update Submitted That Met QC Criteria

April 12, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PZA_WBA

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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