Investigating the Pharmacokinetics of Tafenoquine in Healthy Papua New Guinean Children

NCT07052162 | Recruiting Phase 4

• 1 other identifier: RES67418
• Study Type: interventional
• Target: 30
• 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. 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

Keywords

tafenoquine; vivax malaria; pharmacokinetics; children

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetic: 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 venous blood samples collected at baseline (Day 0), 2, 4, 8, 12, 18, 24, 36 and 48 hours from a sampling cannula with capillary finger-prick samples at Days 3, 4, 7, 14, 28, 42 and 56.

  56-days after drug administration

• Pharmacokinetic: Terminal elimination half-life

  56-days after drug administration

• Pharmacokinetic: Absorption half-life

  56-days after drug administration

• Pharmacokinetics: Clearance

  56-days after drug administration

• Pharmacokinetics: Volume of distribution

  56-days after drug administration

• Pharmacokinetics: Maximal concentration

  56-days after drug administration

• Pharmacokinetics: Area under concentration-time curve

  56-days after drug administration

Secondary Outcomes (6)

• Safety: Change in haemoglobin over 28 days

  28-days from drug administration

• Safety: Change in methaemoglobin over 28 days

  28-days from drug administration

• Safety: Change in hepatorenal function over 7 days

  7-days from drug administration

• Safety: Change in rate corrected QTc over 28 days

  28-days from drug administration

• Tolerability: Taste and tolerability assessment

  1-day following drug administration

Study Arms (2)

Group A

EXPERIMENTAL

Single-dose tafenoquine as 10 mg/kg taken with water and a low-fat meal (3 plain cracker biscuits; 2% fat)

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

Group B

EXPERIMENTAL

Single-dose tafenoquine as 10mg/kg taken with 250 mL chocolate flavoured milk (9% fat) and a low-fat meal (3 plain cracker biscuits; 2% fat).

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

Interventions

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

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

Also known as: TQ, Tafenoquine succinate, Kodatef

Group A

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

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

Also known as: TQ, Tafenoquine succinate, Kodatef

Group B

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• have a normal glucose-6-phosphate-dehydrogenase (G6PD) activity (\>70% enzyme activity) as confirmed by quantitative SD Biosensor
• are Rapid Diagnostic Test negative for malaria
• have not received treatment with any antimalarial in the previous 4-weeks
• have no signs or symptoms of significant morbidity
• have no history of hypersensitivity to primaquine
• are able to attend all scheduled follow-up visits

You may not qualify if:

• have G6PD activity \<70%
• test positive for malaria by rapid diagnostic test
• have receive treatment with an antimalarial in the previous 4-weeks
• have signs or symptoms of significant morbidities
• have a history of primaquine related hypersensitivity
• cannot, or are not willing, to attend all scheduled follow-up visits

Sponsors & Collaborators

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

Study Sites (1)

Alexishafen Health Centre

Madang, Madang Province, MP511, Papua New Guinea

RECRUITING

MeSH Terms

Conditions

Malaria, Vivax

Interventions

tafenoquine; Water; CD36 Antigens

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Platelet Membrane Glycoproteins; Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Fatty Acid Transport Proteins; Membrane Transport Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins; Receptors, Cell Surface; Receptors, Immunologic; Scavenger Receptors, Class B; Receptors, Scavenger; Receptors, LDL; Receptors, Lipoprotein

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: March 27, 2025
• First Posted: July 4, 2025
• Study Start: October 20, 2025
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)