RECRUITINGPhase 4INTERVENTIONAL

Southeast Asia Dose Optimization of Tafenoquine

Optimizing the Dose of Tafenoquine for the Radical Cure of Plasmodium Vivax Malaria in Southeast Asia

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 willing to sign a consent form. - Willing to be followed for 4 months Who Should NOT Join This Trial: - 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) Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

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)

Treatments Being Tested

DRUG

Tafenoquine

Tafenoquine will be given as 100mg coated tablets. Tablets will be given based on weight bands.

DRUG

Chloroquine

Chloroquine will be given as daily dose over 3 days (25mg/kg total dose divided 10/10/5mg/kg)

DRUG

Artemether 20 mg-Lumefantrine 120 mg

Artemether-lumefantrine will be given twice daily over 3 days. Whole tablets will be given based on weight bands.

Locations (5)

Mahidol Oxford Tropical Medicine Research Unit (MORU), Cambodia

Siem Reap, Cambodia

Lao Oxford Mahosot Hospital Wellcome Trust Research Unit (LOMWRU)

Vientiane, Laos

Mahidol Vivax Research Unit (MVRU)

Bangkok, Thailand

Shoklo Malaria Research Unit (SMRU)

Bangkok, Thailand

Oxford University Clinical Research Unit (OUCRU)

Bình Phước, Vietnam