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

NCT ID: NCT02700347

Last Updated: 2017-04-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-29

Study Completion Date

2016-04-30

Brief Summary

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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

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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.

Conditions

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Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Pyrazinamide

Intervention Type DRUG

Allopurinol

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Pyrazinamide

Intervention Type DRUG

Allopurinol

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Pyrazinamide

Intervention Type DRUG

Allopurinol

Intervention Type DRUG

Interventions

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Pyrazinamide

Intervention Type DRUG

Allopurinol

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National University Hospital, Singapore

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nicholas Paton

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

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National University Hospital, Singapore

Singapore, , Singapore

Site Status

Countries

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Singapore

References

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Naftalin CM, Verma R, Gurumurthy M, Lu Q, Zimmerman M, Yeo BCM, Tan KH, Lin W, Yu B, Dartois V, Paton NI. Coadministration of Allopurinol To Increase Antimycobacterial Efficacy of Pyrazinamide as Evaluated in a Whole-Blood Bactericidal Activity Model. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00482-17. doi: 10.1128/AAC.00482-17. Print 2017 Oct.

Reference Type DERIVED
PMID: 28739782 (View on PubMed)

Other Identifiers

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PZA_WBA

Identifier Type: -

Identifier Source: org_study_id

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