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

Phase 1 Completed 12 enrolled National University Hospital, Singapore

RandomizedParallel-groupOpen-labelTreatment

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.

Timeline

Start: 2016-02
Primary completion: 2016-04
Completion: 2016-04

Outcome

Missed primary endpoint

paper mean cumulative WBA (0.01 ± 0.02 ΔlogCFU versus 0.00 ± 0.02 ΔlogCFU for PZA alone versus PZA plus allopurinol) (P = 0.49). PMID 28739782 ↗

Publications

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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Allopurinol	Small molecule	100 mg	—
Subject	Pyrazinamide	Small molecule	10 mg/kg	—
Subject	Pyrazinamide	Small molecule	25 mg/kg	—
Subject	Pyrazinamide	Small molecule	35 mg/kg	—