Investigating the Pharmacology of Tafenoquine in Papua New Guinean Children With Uncomplicated Malaria

NCT07403643 | Not Yet Recruiting Phase 4

• 1 other identifier: RES67418-B
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. Furthermore, early data suggest a drug interaction between TQ and artemisinin combination therapy (ACT) drugs - which requires further investigation and confirmation. This study will generate critical paediatric safety, tolerability, pharmacokinetic, and preliminary efficacy data for TQ when administered with either artemether-lumefantrine or dihydroartemisinin-piperaquine in PNG children with uncomplicated malaria.

Conditions

Uncomplicated Malaria

Keywords

tafenoquine; vivax malaria; radical cure; pharmacokinetics; children

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetic: Tafenoquine terminal elimination half-life

  Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.

  56-days after tafenoquine administration

• Pharmacokinetic: Tafenoquine distribution half-life

  Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.

  56-days after tafenoquine administration

• Pharmacokinetic: Tafenoquine absorption half-life

  Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.

  56-days after tafenoquine administration

• Pharmacokinetics: Tafenoquine clearance

  Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.

  56-days after tafenoquine administration

• Pharmacokinetics: Tafenoquine volume of distribution

  Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.

  56-days after tafenoquine administration

• Pharmacokinetic: Tafenoquine maximal concentration

  Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.

  56-days after tafenoquine administration

• Pharmacokinetics: Tafenoquine area under concentration-time curve

  Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.

  56-days after tafenoquine administration

Secondary Outcomes (7)

• Safety: Change in haemoglobin over 84 days

  84-days from tafenoquine administration

• Safety: Change in methaemoglobin over 28 days

  28-days from drug administration.

• Safety: Change in hepatorenal function over 28 days

  28-days from tafenoquine administration

• Safety: Change in rate corrected QTc over 28 days

  28-days from tafenoquine administration

• Efficacy: PCR adjusted Day-28 P. vivax relapse efficacy

  28-days from tafenoquine administration

Study Arms (2)

Group A: Tafenoquine + Artemether-Lumefantrine

EXPERIMENTAL

Single-dose tafenoquine as 10 mg/kg given with the first dose of artemether-lumefantrine treatment regimen (ARM 1.7 mg/kg and LUM 10 mg/kg, twice daily for 3 days) with water and a low-fat meal

Drug: Single dose tafenoquine (10 mg/kg); Drug: Artemether + Lumefantrine

Group B: Tafenoquine + Dihydroartemisinin-piperaquine

EXPERIMENTAL

Single-dose tafenoquine as 10 mg/kg given with the first dose of dihydroartemisinin-piperaquine (DHA 2.5 mg/kg and PQ phosphate 20 mg/kg, once daily for 3 days) with water and a low-fat meal

Drug: Single dose tafenoquine (10 mg/kg); Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)

Interventions

Single dose tafenoquine (10 mg/kg) DRUG

Participants will receive single-dose TQ as 10 mg/kg given with the first dose of ACT. Food (low-fat meal) is taken 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, and will receive the remaining treatment course of their randomized ACT as for PNG Standard Treatment Guidelines.

Also known as: Tafenoquine succinate, TQ, Kodatef

Group A: Tafenoquine + Artemether-Lumefantrine; Group B: Tafenoquine + Dihydroartemisinin-piperaquine

Dihydroartemisinin-piperaquine (DHA-PPQ) DRUG

Participants will receive dihydroartemisinin-piperaquine (DHA 2.5 mg/kg and PQ phosphate 20 mg/kg), once daily for 3 days with water and a low-fat meal. 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.

Also known as: DP, DHA-PPQ, Eurartesim

Group B: Tafenoquine + Dihydroartemisinin-piperaquine

Artemether + Lumefantrine DRUG

Participants will receive artemether-lumefantrine (ARM 1.7 mg/kg and LUM 10 mg/kg) twice daily for 3 days with water and a low-fat meal. Combinations of full or half-tablets will be swallowed whole or crushed lightly (tablets) or dissolved in boiled water (if dispersible tablets are available). Morning doses will be observed as directly observed treatment, with evening doses dispensed to the parent/guardian each day. Parents will be asked to report approximate time of evening dosing the following morning, and return any pills that were not successfully administered.

Also known as: ARM-LUM, Mala1, Coartem

Group A: Tafenoquine + Artemether-Lumefantrine

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Have normal G6PD activity (\>70% enzyme activity) as confirmed by quantitative SD Biosensor
• Do not have severe malaria (by WHO criteria)
• Have rapid diagnostic test and/or microscopically confirmed uncomplicated malaria (any species)
• Have no significant co-morbidity
• Have no history of hypersensitivity to primaquine
• Have no history of hypersensitivity to artemether-lumefantrine or dihydroartemisinin-piperaquine
• Are able to attend all scheduled follow-up visits

You may not qualify if:

• Have \<70% G6PD enzyme activity, as confirmed by quantitative SD Biosensor
• Have signs or symptoms of severe malaria (by WHO criteria)
• Test negative for malaria by rapid diagnostic test and/or microscopy
• Have signs or symptoms of a significant co-morbidity
• Have a history of hypersensitivity to primaquine
• Have a history of hypersensitivity to artemether-lumefantrine or dihydroartemisinin-piperaquine
• Cannot, or are not willing, to attend all scheduled follow-up visits

Sponsors & Collaborators

• Curtin University: lead
• Papua New Guinea Institute of Medical Research: collaborator
• The University of Western Australia: collaborator

Study Sites (1)

Alexishafen Health Centre

Madang, Madang Province, MP511, Papua New Guinea

Location

MeSH Terms

Conditions

Malaria, Vivax

Interventions

tafenoquine; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Brioni R Moore, PhD

  Curtin University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brioni R Moore, PhD

CONTACT

+61 8 9266 2956; brioni.moore@curtin.edu.au

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 11, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)