NCT02700347

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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Feb 2016

Shorter than P25 for phase_1

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

February 1, 2016

Completed
23 days until next milestone

First Submitted

Initial submission to the registry

February 24, 2016

Completed
12 days until next milestone

First Posted

Study publicly available on registry

March 7, 2016

Completed
25 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

April 13, 2017

Status Verified

April 1, 2017

Enrollment Period

2 months

First QC Date

February 24, 2016

Last Update Submit

April 12, 2017

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

  • Cumulative whole blood bactericidal activity (WBA)

    Cumulative bactericidal activity calculated as log change CFU.day

    48 hours

Secondary Outcomes (3)

  • 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

Study Arms (3)

Low dose pyrazinamide

EXPERIMENTAL

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: PyrazinamideDrug: Allopurinol

Standard dose pyrazinamide

EXPERIMENTAL

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: PyrazinamideDrug: Allopurinol

High dose pyrazinamide

EXPERIMENTAL

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: PyrazinamideDrug: Allopurinol

Interventions

PyrazinamideDRUG
High dose pyrazinamideLow dose pyrazinamideStandard dose pyrazinamide
AllopurinolDRUG
High dose pyrazinamideLow dose pyrazinamideStandard dose pyrazinamide

Eligibility Criteria

Age21 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National University Hospital, Singapore

Singapore, Singapore

Location

Related Publications (1)

  • 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.

    PMID: 28739782DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

PyrazinamideAllopurinol

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Intervention Hierarchy (Ancestors)

PyrazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Nicholas Paton

    National University Hospital, Singapore

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 24, 2016

First Posted

March 7, 2016

Study Start

February 1, 2016

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

April 13, 2017

Record last verified: 2017-04

Locations

SG(1)