Investigation of Short Course, High Dose Primaquine Treatment for Liver Stages of Plasmodium Vivax Infection

Summary

This study specifically seeks to provide data on the safety, tolerability and pilot efficacy of short course, high dose primaquine treatment in Papua New Guinean children aged 5-10 years, in a cross-sectional study design. Community screened asymptomatic cases and/or cases of clinically diagnosed malaria admitted to the out-patient units of the health center, will be screened for Glucose-6-phosphate dehydrogenase deficiency (G6PD) and malaria illness by rapid diagnostic test and P. vivax infection confirmed by light microscopy. Following treatment with artemether-lumefantrine (Coartem), G6PD normal children will be enrolled into the study and followed for 2 months. Primaquine treatment will be allocated to study participants in a step-wise design; firstly receiving the current 14 day treatment regimen of 0.5 mg/kg total dose (n=40); secondly, a 7 day treatment regimen receiving a total dose of 1.0 mg/kg/day; then thirdly, receive 1.0 mg/kg twice daily dose (bd) for a total of 3.5 days, should the 7 day treatment prove to be safe and well tolerated. In addition to this dose-escalation study, the pharmacokinetic profiles of single doses of 0.5 mg/kg and 1.0 mg/kg will be determined using an intensive sampling protocol, in children aged 5-10 years. The pharmacokinetic profiles obtained by this sub-study will be essential for modeling the population pharmacokinetic data obtained from the dose-escalation study. As there is currently no data on the safety, tolerability and efficacy of primaquine in children, the present study will validate previous observation and contribute to the knowledge of primaquine as a treatment for liver stages of Plasmodium vivax infection.

Conditions

• Plasmodium Vivax

Interventions

DRUG

Primaquine

Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40)

Sponsors & Collaborators

• Walter and Eliza Hall Institute of Medical Research

  collaborator OTHER

• The University of Western Australia

  collaborator OTHER

• University of Oxford

  collaborator OTHER

• Curtin University

  collaborator OTHER

• Papua New Guinea Institute of Medical Research

  lead OTHER_GOV

Principal Investigators

• Inoni Betuela, MD, PhD · PNG Institute of Medical Research

• Ivo Mueller, PhD · Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)

• J Kevin Baird, PhD · Eijkman-Oxford Clinical Research Unit, Oxford University

• Timothy ME Davis, FRAC, PhD · The University of Western Australia

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

5 Years

Max Age

10 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-06-30

Primary Completion

2016-06-30

Completion

2016-12-31

Countries

• Papua New Guinea

Study Locations