Investigating the Pharmacokinetics of Tafenoquine in Healthy Papua New Guinean Children

Summary

Plasmodium vivax is the most geographically widespread malaria species and the second largest contributor to symptomatic malaria worldwide. It accounts for half of all malaria cases outside Africa, with an estimated 14.3 million clinical vivax malaria cases reported annually, contributing to an annual cost of US$359 million. Children are most vulnerable to infection, with P. vivax prevalence peaking between 2 to 6 years of age. In Papua New Guinea (PNG), there are \>1.5 million suspected P. vivax cases annually, and while P. falciparum infections are the most prevalent, P. vivax transmission is the most intense in the world. P. vivax in PNG provides a unique epidemiological setting in which to assess innovative treatments in children.

The complex biology of P. vivax represents a challenge for malaria control and chemotherapy, especially dormant liver-stage parasites (hypnozoites) which can reactivate (relapse) and cause disease at a time remote from the primary infection. Hypnozoite relapse is the primary cause of vivax malaria in endemic regions and is resistant to most antimalarial drugs. Identifying effective treatments for radical cure, the complete elimination of parasites (both blood- and liver-stage), is therefore a priority. The World Health Organization (WHO) recommends a 14-day radical cure regimen for uncomplicated vivax malaria; comprised of blood stage treatment (chloroquine or artemisinin combination therapy (ACT)) and 14 days of the 8-aminoquinoline drug primaquine (PQ; 0.25-0.5 mg/kg/day) for liver-stage cure. More recently, the 8-aminoquinoline tafenoquine has garnered interest as an alternative radical cure agent to primaquine. However, there is limited data on the pharmacokinetics, tolerability and radical cure efficacy of tafenoquine in children.

The overall aim of the study is to characterise the pharmacokinetic profile of tafenoquine (and primary metabolite) in Papua New Guinean children.

Conditions

• Pharmacokinetics of Tafenoquine

Interventions

DRUG

Single dose tafenoquine (10 mg/kg) given with water

Participants will receive single-dose TQ as 10 mg/kg taken with water and a low-fat meal (3 plain cracker biscuits; 2% fat). Food (low-fat meal) is taken with both regimens to attenuate any gastrointestinal adverse effects that are related to taking TQ on an empty stomach. Combinations of full or half-tablets will be swallowed whole or crushed lightly (tablets) or dissolved in boiled water (if dispersible tablets are available), as directly observed treatment. Children vomiting within the first 30 minutes of treatment will be withdrawn

DRUG

Single dose tafenoquine (10 mg/kg) given with fat

Single-dose TQ as 10 mg/kg taken with 250 mL chocolate flavoured milk (9% fat) and a low-fat meal (3 plain cracker biscuits). Food (low-fat meal) is taken with both regimens to attenuate any gastrointestinal adverse effects that are related to taking TQ on an empty stomach. Combinations of full or half-tablets will be swallowed whole or crushed lightly (tablets) or dissolved in boiled water (if dispersible tablets are available), as directly observed treatment. Children vomiting within the first 30 minutes of treatment will be withdrawn

Sponsors & Collaborators

• Papua New Guinea Institute of Medical Research

  collaborator OTHER_GOV

• The University of Western Australia

  collaborator OTHER

• Curtin University

  lead OTHER

Principal Investigators

• Brioni R Moore, PhD · Curtin University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

5 Years

Max Age

12 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-10-20

Primary Completion

2026-03-31

Completion

2026-03-31

Countries

• Papua New Guinea

Study Locations