Uncomplicated MalariaPhase 4NCT07403643
Investigating the Pharmacology of Tafenoquine in Papua New Guinean Children With Uncomplicated Malaria
A Phase 4 study testing Single dose tafenoquine (10 mg/kg), Dihydroartemisinin-piperaquine (DHA-PPQ) and Artemether + Lumefantrine in people with Uncomplicated Malaria, run by Curtin University at 1 site in Papua New Guinea.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 12 years
- Conditions the study is for
- Uncomplicated Malaria
- What is being tested?
- Single dose tafenoquine (10 mg/kg), Dihydroartemisinin-piperaquine (DHA-PPQ) and Artemether + Lumefantrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 sitePapua New Guinea
- Study dates
- Apr 2026to Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Papua New Guinea1 site
Alexishafen Health Centre
Madang, Madang Province, MP511
Paula Tesine, MD, +675 852 2909, paula.tesine@pngimr.org.pg
About this study
Official title: Safety, Pharmacokinetics, and Preliminary Efficacy of Tafenoquine for the Treatment of Vivax Malaria in Papua New Guinean Children
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.
Read the detailed description
This is an open-label study to evaluate the safety, tolerability, pharmacokinetic disposition and preliminary efficacy of tafenoquine, when co-administered as part of a radical cure regimen with two artemisinin combination therapies in Papua New Guinean children with uncomplicated malaria. This study represents the second part of a multi-phase investigation of tafenoquine in PNG children (Study 1: NCT07052162). In this study, children aged 2 to 12 years will be eligible for inclusion in the study providing they have uncomplicated malaria (P. falciparum and/or P. vivax malaria; confirmed by rapid diagnostic test and/or microscopy), normal G6PD activity (>70% enzyme activity by SD Biosensor), no evidence of severe malaria, no significant comorbidity, and no history of previous hypersensitivity to 8-aminoquinolines, artemether-lumefantrine or dihydroartemisinin-piperaquine. All participants will be admitted to the Alexishafen Health Centre for the first 24-hours of the study, to facilitate blood sampling and clinical monitoring. After admission, baseline demographic and medical history will be taken, and the participants will undergo a full clinical assessment to establish baseline safety indices. The 60 participants will then be randomized 1:1 to receive either i) single-dose TQ as 10 mg/kg given with the first dose of artemether-lumefantrine treatment regimen (Coartem®; ARM 1.7 mg/kg and LUM 10 mg/kg, twice daily for 3 days) with water and a low-fat meal (unless indicated otherwise in Study 1), or ii) single-dose TQ as 10 mg/kg given with the first dose of dihydroartemisinin-piperaquine (Eurartesim®; DHA 2.5 mg/kg and PQ phosphate 20 mg/kg, once daily for 3 days) with water and a low-fat meal (unless indicated otherwise in Study 1). For pharmacokinetic analysis, each participant will be allocated a randomised sampling schedule with dried blood spots for pharmacokinetic analysis performed at 6 of 15 time points (2, 4, 8, 12, 18, 24, 38 and 48 hours, Days 3, 4, 7, 14, 28, 42 and 56). At each allocated time point, 0.5 mL samples will be collected by finger-prick with five 50 µL blood drops spotted on to Whatman Protein 903 cards for dried blood spot analysis. The remaining blood will be collected into lithium heparin anticoagulant. Both dried blood spot and plasma samples will be collected at all time points for pharmacokinetic analyses. Standardised review, including adverse-effect questionnaires, and clinical monitoring (haemoglobin, methaemoglobin, reticulocyte counts, malaria blood films) will be conducted at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). Safety testing (hepatorenal function tests (ALT, total bilirubin, creatinine), haemoglobin, urine dipstick analysis and electrocardiogram trace, will be taken at 4, 24 hours and on Days 3, 7 and 28.
The primary aim of the study is to characterise the pharmacokinetic profile of TQ (and its primary metabolite) in PNG children.
Secondary objectives include;
- To assess the safety of TQ in PNG children
- To assess the preliminary relapse efficacy of TQ given with artemether-lumefantrine.
- To assess the preliminary relapse efficacy of TQ given with dihydroartemisinin-piperaquine.
- To assess the tolerability of TQ in PNG children.
The investigators hypothesise that:
- A single TQ 10 mg/kg dose is safe and efficacious for use in children with uncomplicated malaria.
- TQ has no clinically relevant effects on the pharmacokinetics of artemether, lumefantrine, or their metabolites.
- Cut or crushed tablets will not be well tolerated, although tolerability will improve with administration of whole tablets or dispersible tablets.
- Conditions
- Uncomplicated Malaria
- Being tested
- Single dose tafenoquine (10 mg/kg), Dihydroartemisinin-piperaquine (DHA-PPQ), Artemether + Lumefantrine
- Keywords
- tafenoquine, vivax malaria, radical cure, pharmacokinetics, children
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single dose tafenoquine (10 mg/kg)Drug
Also called Tafenoquine succinate, TQ, Kodatef
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.
Dihydroartemisinin-piperaquine (DHA-PPQ)Drug
Also called DP, DHA-PPQ, Eurartesim
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.
Artemether + LumefantrineDrug
Also called ARM-LUM, Mala1, Coartem
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Single dose tafenoquine (10 mg/kg); Drug: Dihydroartemisinin-piperaquine (DHA-PPQ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 56-days after tafenoquine administration
Secondary outcomes (7)
Safety: Change in haemoglobin over 84 days
A fingerprick blood sample will be drawn at baseline to determine pre-treatment haemoglobin concentration (point-of-care HemoCue Hb201+, Radiometer, Australia). To monitor for post-treatment haemolysis, fingerprick haemoglobin samples will be taken at safety time points (4 and 24 hours, and on days 3, 7 and 28 post tafenoquine dosing) and all standardised review time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84).
Measured: 84-days from tafenoquine administration
Safety: Change in methaemoglobin over 28 days
Methaemoglobin will be assessed by a Rad57 pulse oximeter with SpMet function (Masimo, USA) at all defined safety time points (4 and 24 hours) and standardised review time points (Days 0, 1, 2, 3, 4, 7, 14, and 28).
Measured: 28-days from drug administration.
Safety: Change in hepatorenal function over 28 days
Hepatorenal function (creatinine, total bilirubin and alanine transaminase [ALT]) will be analysed on a Fuji Dri-Chem NX500 analyser (Fujifilm, Japan). 100 µL fingerprick blood samples will be collected at baseline, 4 and 24 hours, and on Days 3, 7 and 28 after tafenoquine dosing.
Measured: 28-days from tafenoquine administration
Safety: Change in rate corrected QTc over 28 days
A 12-lead electrocardiogram will be conducted at baseline, 4 and 24 hours, and on Days 3, 7 and 28 after tafenoquine dosing to determine change in rate corrected QTc.
Measured: 28-days from tafenoquine administration
Efficacy: PCR adjusted Day-28 P. vivax relapse efficacy
Blood smears for malarial microscopy and dried blood spots for molecular parasitology will be carried out at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). All blood films for malarial microscopy will be examined by two skilled microscopists blinded to treatment. Slides discrepant for positivity/negativity, speciation or parasitaemia (>3x difference) will be adjudicated by a senior microscopist. Quantitative multi-species PCR will be assayed (using validated methods) on all collected samples to confirm outcomes from malarial microscopy, and report PCR adjusted relapse efficacy.
Measured: 28-days from tafenoquine administration
Efficacy: PCR adjusted Day-42 P. vivax relapse efficacy
Blood smears for malarial microscopy and dried blood spots for molecular parasitology will be carried out at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). All blood films for malarial microscopy will be examined by two skilled microscopists blinded to treatment. Slides discrepant for positivity/negativity, speciation or parasitaemia (>3x difference) will be adjudicated by a senior microscopist. Quantitative multi-species PCR will be assayed (using validated methods) on all collected samples to confirm outcomes from malarial microscopy, and report PCR adjusted relapse efficacy.
Measured: 42-days from tafenoquine administration
Efficacy: PCR adjusted Day-84 P. vivax relapse efficacy
Blood smears for malarial microscopy and dried blood spots for molecular parasitology will be carried out at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). All blood films for malarial microscopy will be examined by two skilled microscopists blinded to treatment. Slides discrepant for positivity/negativity, speciation or parasitaemia (>3x difference) will be adjudicated by a senior microscopist. Quantitative multi-species PCR will be assayed (using validated methods) on all collected samples to confirm outcomes from malarial microscopy, and report PCR adjusted relapse efficacy.
Measured: 84-days after tafenoquine administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study startApr 2026 (estimated)
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uncomplicated MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Curtin University
- Sponsor type
- University, hospital or other
- Collaborators
- Papua New Guinea Institute of Medical Research, The University of Western Australia
- Responsible party
- Sponsor
- Investigators
- Brioni R Moore, PhD, Principal investigator, Curtin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07403643
- Sponsor's protocol ID
- RES67418-B
- Status last verified
- Feb 2026
- First submitted
- 4 Feb 2026
- Last updated
- 12 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data may be shared upon contact with the principal investigators and approval by the PNG Institute of Medical Research. This process will be conducted on a case by case basis, as per agreements between collaborative partners.
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Pharmacokinetics, and Preliminary Efficacy of Tafenoquine for the Treatment of Vivax Malaria in Papua New Guinean Children
- ClinicalTrials.gov ID
- NCT07403643
- Acronym / sponsor ID
- RES67418-B
- Conditions
- Uncomplicated Malaria
- Keywords
- tafenoquine, vivax malaria, radical cure, pharmacokinetics, children
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Curtin UniversityUniversity, hospital or other
- Collaborators
- Papua New Guinea Institute of Medical Research, The University of Western Australia
- Study start
- Apr 2026 (estimated)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 11 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an open-label study to evaluate the safety, tolerability, pharmacokinetic disposition and preliminary efficacy of tafenoquine, when co-administered as part of a radical cure regimen with two artemisinin combination therapies in Papua New Guinean children with uncomplicated malaria. This study represents the second part of a multi-phase investigation of tafenoquine in PNG children (Study 1: NCT07052162). In this study, children aged 2 to 12 years will be eligible for inclusion in the study providing they have uncomplicated malaria (P. falciparum and/or P. vivax malaria; confirmed by rapid diagnostic test and/or microscopy), normal G6PD activity (>70% enzyme activity by SD Biosensor), no evidence of severe malaria, no significant comorbidity, and no history of previous hypersensitivity to 8-aminoquinolines, artemether-lumefantrine or dihydroartemisinin-piperaquine. All participants will be admitted to the Alexishafen Health Centre for the first 24-hours of the study, to facilitate blood sampling and clinical monitoring. After admission, baseline demographic and medical history will be taken, and the participants will undergo a full clinical assessment to establish baseline safety indices. The 60 participants will then be randomized 1:1 to receive either i) single-dose TQ as 10 mg/kg given with the first dose of artemether-lumefantrine treatment regimen (Coartem®; ARM 1.7 mg/kg and LUM 10 mg/kg, twice daily for 3 days) with water and a low-fat meal (unless indicated otherwise in Study 1), or ii) single-dose TQ as 10 mg/kg given with the first dose of dihydroartemisinin-piperaquine (Eurartesim®; DHA 2.5 mg/kg and PQ phosphate 20 mg/kg, once daily for 3 days) with water and a low-fat meal (unless indicated otherwise in Study 1). For pharmacokinetic analysis, each participant will be allocated a randomised sampling schedule with dried blood spots for pharmacokinetic analysis performed at 6 of 15 time points (2, 4, 8, 12, 18, 24, 38 and 48 hours, Days 3, 4, 7, 14, 28, 42 and 56). At each allocated time point, 0.5 mL samples will be collected by finger-prick with five 50 µL blood drops spotted on to Whatman Protein 903 cards for dried blood spot analysis. The remaining blood will be collected into lithium heparin anticoagulant. Both dried blood spot and plasma samples will be collected at all time points for pharmacokinetic analyses. Standardised review, including adverse-effect questionnaires, and clinical monitoring (haemoglobin, methaemoglobin, reticulocyte counts, malaria blood films) will be conducted at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). Safety testing (hepatorenal function tests (ALT, total bilirubin, creatinine), haemoglobin, urine dipstick analysis and electrocardiogram trace, will be taken at 4, 24 hours and on Days 3, 7 and 28.
The primary aim of the study is to characterise the pharmacokinetic profile of TQ (and its primary metabolite) in PNG children.
Secondary objectives include;
- To assess the safety of TQ in PNG children
- To assess the preliminary relapse efficacy of TQ given with artemether-lumefantrine.
- To assess the preliminary relapse efficacy of TQ given with dihydroartemisinin-piperaquine.
- To assess the tolerability of TQ in PNG children.
The investigators hypothesise that:
- A single TQ 10 mg/kg dose is safe and efficacious for use in children with uncomplicated malaria.
- TQ has no clinically relevant effects on the pharmacokinetics of artemether, lumefantrine, or their metabolites.
- Cut or crushed tablets will not be well tolerated, although tolerability will improve with administration of whole tablets or dispersible tablets.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: Tafenoquine + Artemether-Lumefantrine | Experimental | Drug: Single dose tafenoquine (10 mg/kg), Drug: Artemether + LumefantrineSingle-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 |
| Group B: Tafenoquine + Dihydroartemisinin-piperaquine | Experimental | Drug: Single dose tafenoquine (10 mg/kg), Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)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 |
Who may qualify
- Ages
- 2 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single dose tafenoquine (10 mg/kg)Also: Tafenoquine succinate, TQ, KodatefParticipants 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. | Drug | Group A: Tafenoquine + Artemether-Lumefantrine, Group B: Tafenoquine + Dihydroartemisinin-piperaquine |
| Dihydroartemisinin-piperaquine (DHA-PPQ)Also: DP, DHA-PPQ, EurartesimParticipants 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. | Drug | Group B: Tafenoquine + Dihydroartemisinin-piperaquine |
| Artemether + LumefantrineAlso: ARM-LUM, Mala1, CoartemParticipants 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. | Drug | Group A: Tafenoquine + Artemether-Lumefantrine |
Primary outcome
Pharmacokinetic: Tafenoquine terminal elimination half-life
Time frame: 56-days after tafenoquine administration
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.
Pharmacokinetic: Tafenoquine distribution half-life
Time frame: 56-days after tafenoquine administration
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.
Pharmacokinetic: Tafenoquine absorption half-life
Time frame: 56-days after tafenoquine administration
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.
Pharmacokinetics: Tafenoquine clearance
Time frame: 56-days after tafenoquine administration
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.
Pharmacokinetics: Tafenoquine volume of distribution
Time frame: 56-days after tafenoquine administration
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.
Pharmacokinetic: Tafenoquine maximal concentration
Time frame: 56-days after tafenoquine administration
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.
Pharmacokinetics: Tafenoquine area under concentration-time curve
Time frame: 56-days after tafenoquine administration
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.
7 secondary outcomes
Safety: Change in haemoglobin over 84 days
Time frame: 84-days from tafenoquine administration
Safety: Change in methaemoglobin over 28 days
Time frame: 28-days from drug administration.
Safety: Change in hepatorenal function over 28 days
Time frame: 28-days from tafenoquine administration
Safety: Change in rate corrected QTc over 28 days
Time frame: 28-days from tafenoquine administration
Efficacy: PCR adjusted Day-28 P. vivax relapse efficacy
Time frame: 28-days from tafenoquine administration
Efficacy: PCR adjusted Day-42 P. vivax relapse efficacy
Time frame: 42-days from tafenoquine administration
Efficacy: PCR adjusted Day-84 P. vivax relapse efficacy
Time frame: 84-days after tafenoquine administration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
- Individual participant dataSharing planned: No. Data may be shared upon contact with the principal investigators and approval by the PNG Institute of Medical Research. This process will be conducted on a case by case basis, as per agreements between collaborative partners.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brioni R Moore, PhD principal investigator
Curtin University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Single dose tafenoquine (10 mg/kg), Dihydroartemisinin-piperaquine (DHA-PPQ) and Artemether + Lumefantrine in people with Uncomplicated Malaria, run by Curtin University at 1 site in Papua New Guinea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Papua New Guinea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Brioni R Moore, PhD (+61 8 9266 2956, brioni.moore@curtin.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic: Tafenoquine terminal elimination half-life (time frame: 56-days after tafenoquine administration). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2026.