Southeast Asia Dose Optimization of Tafenoquine

Tafenoquine was recently approved by regulatory authorities in the USA and Australia. Tafenoquine is an alternative radical curative treatment to primaquine acting against the dormant liver stage of Plasmodium vivax (the hypnozoite). Tafenoquine (an 8-aminoquinoline) has the substantial advantage of single dosing as compared to a 14-day course of primaquine to achieve radical cure. The recommended tafenoquine dose is 300 mg, which was shown to be significantly worse in radical curative efficacy to a total primaquine dose of 3.5 mg/kg in Southeast Asia. The cure rate of tafenoquine 300 mg in Southeast Asian study sites was only 74%. The comparator 3.5 mg/kg total primaquine dose is the standard and most commonly used dose globally, but in Southeast Asia and the Western Pacific, higher doses of primaquine are needed for radical cure. This study aims to determine the optimal dose of tafenoquine in Southeast Asia. Addendum for Indonesia: The INSPECTOR trial results showed that tafenoquine 300mg was not efficacious for radical cure (79% probability for recurrence after treatment). The comparator arm, low-dose primaquine 3.5mg/kg divided equally over 14 days, showed a 48% probability of recurrence after treatment). The standard of care for radical cure in Indonesia is high-dose primaquine 7mg/kg divided in 7 daily doses).

Inclusion Criteria: * Patients with symptomatic P. vivax mono-infection as diagnosed by microscopy * Fever or history of fever in the previous 7 days * Quantitative G6PD activity ≥70% of the population median * Weight \>10 kg and ≥2 years old * Ability to understand the study instructions and provide written informed consent. * Willing to be followed for 4 months Exclusion Criteria: * Pregnancy * Lactation * Hb \< 8 g/dL * Severe malaria * Blood transfusion in the last 4 months * History of allergic response to an 8-aminoquinoline or the nationally recommended schizonticide (e.g., chloroquine, artemether-lumefantrine) * Any previous history of a haemolytic event Presence of any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study (e.g. chronic disease, medications that potentiate or inhibit CYP2D6 or CYP2C8 isoenzyme function)