A Randomized, Double-blind, Placebo-controlled Evaluation of Increasing Doses of Weekly Tafenoquine for Chemosuppression of Plasmodium Falciparum

Study Overview
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Brief Summary
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This was a randomised, double-blind, placebo-controlled study to compare the efficacy of a range four weekly doses of tafenoquine, and weekly mefloquine, with placebo as chemosuppression of P. falciparum malaria. Medications and placebo were matched and a double-dummy technique enabled blinding of tafenoquine versus mefloquine.

Official Title
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A Randomized, Double-blind, Placebo-controlled Evaluation of Increasing Doses of Weekly Tafenoquine for Chemosuppression of Plasmodium Falciparum in Semi-immune Adults Living in the Kassena-Nankana District of Northern Ghana

Conditions
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Malaria

Intervention / Treatment
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* Drug: Placebo
* Drug: Tafenoquine 25mg
* Drug: Tafenoquine 50mg
* Drug: Tafenoquine 100 mg
* Drug: Tafenoquine 200 mg
* Drug: Mefloquine 250 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing subjects in good general health. Males aged 18 to 60; females aged 50 to 60. Subjects who planned to stay in the study area until the end of the study. Exclusion Criteria: Subjects with any cardiovascular, liver, neurologic, or renal function abnormality which, in the opinion of the clinical investigators, would have placed them at increased risk of an adverse event or confused the result. Subjects with a personal or family history of seizures or frank psychiatric disorder. Females who had not ceased menstruation; a urine β-human chorionic gonadotrophin (β-HCG) test was to be performed at screening females who had ceased menstruation to exclude pregnancy as a cause. Females who were lactating. Subjects given antimalarial drugs for treatment within two weeks of study drug initiation. Subjects with clinically significant abnormalities (to include but not limited to abnormal hepatic or renal function) as determined by history, physical and routine blood chemistry and haematology values. Subjects with known hypersensitivity to any of the study drugs. Subjects unwilling to remain in the area, report for drug administration or blood drawing during the 3-4 month duration of the study. Subjects with G6PD deficiency (as determined by two separate qualitative tests per subject administered using distinct methods; methods used were visual dye and filter paper methods). Subjects with any of the following laboratory values: haemoglobin (Hb) <8g/dL, platelets <80,000/mm3, white blood cell count (WBC) <3000/mm3, creatinine >1.5mg/dL, alanine transaminase (ALT) >60IU or 1+ haematuria as detected by urine dipstick.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose. | Drug: Placebo<br>* Placebo<br>|
| Experimental: Tafenoquine 25mg<br>Tafenoquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose. | Drug: Tafenoquine 25mg<br>* Tafenoquine 25mg<br>|
| Experimental: Tafenoquine 50mg<br>Tafenoquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose. | Drug: Tafenoquine 50mg<br>* Tafenoquine 50mg<br>|
| Experimental: Tafenoquine 100 mg<br>Tafenoquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose. | Drug: Tafenoquine 100 mg<br>* Tafenoquine 100 mg<br>|
| Experimental: Tafenoquine 200 mg<br>Tafenoquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose. | Drug: Tafenoquine 200 mg<br>* Tafenoquine 200 mg<br>|
| Experimental: Mefloquine 250 mg<br>Mefloquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose. | Drug: Mefloquine 250 mg<br>* Mefloquine 250 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First occurrence of malaria infection | First occurrence of malaria infection as documented by a positive malaria smear. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to confirmation of parasitaemia | Time to confirmation of parasitaemia as documented by two consecutive positive smears and the incidence density of parasitaemia. | 16 weeks |