Tuberculosis
Conditions
Brief 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.
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.
Interventions
DRUGPyrazinamide
DRUGAllopurinol
Sponsors
National University Hospital, Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative whole blood bactericidal activity (WBA) | 48 hours | Cumulative bactericidal activity calculated as log change CFU.day |
Secondary
| Measure | Time frame |
|---|---|
| Plasma concentrations of study drugs to determine the Area Under the Curve (AUC) | 48 hours |
| Plasma concentrations of study drugs to determine the Maximum Plasma Concentration (Cmax) | 48 hours |
| Plasma concentrations of study drugs to determine the drug half-life (t1/2) | 48 hours |
Countries
Singapore
Outcome results
None listed