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

Tuberculosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02700347
• Other study ID #: PZA_WBA
• Status: Completed
• Phase: Phase 1
• First received: February 24, 2016
• Last updated: April 12, 2017
• Start date: February 2016
• Est. completion date: April 2016

Study information

• Verified date: April 2017
• Source: National University Hospital, Singapore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Mycobacterium Infections
• Tuberculosis

Intervention

Drug:
• Pyrazinamide

• Allopurinol

Locations

Country	Name	City	State
Singapore	National University Hospital, Singapore	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National University Hospital, Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative whole blood bactericidal activity (WBA)	Cumulative bactericidal activity calculated as log change CFU.day	48 hours
Secondary	Plasma concentrations of study drugs to determine the Area Under the Curve (AUC)		48 hours
Secondary	Plasma concentrations of study drugs to determine the Maximum Plasma Concentration (Cmax)		48 hours
Secondary	Plasma concentrations of study drugs to determine the drug half-life (t1/2)		48 hours