A randomized, double-blind, placebo-controlled,
dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium
falciparum.
Hale BR, Owusu-Agyei S, Fryauff DJ, Koram KA, Adjuik M, Oduro AR, Prescott WR,
Baird JK, Nkrumah F, Ritchie TL, Franke ED, Binka FN, Horton J, Hoffman SL.
US Navy Medical Research Unit No. 3, Cairo, Egypt.
Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for
malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate
dehydrogenase (G6PD) function. A randomized, double-blind, placebo-controlled
chemoprophylaxis trial was conducted with adult residents of northern Ghana to
determine the minimum effective weekly dose of tafenoquine for the prevention of
infection by Plasmodium falciparum. The primary end point was a positive malaria
blood smear result during the 13 weeks of study drug coverage. Relative to the
placebo, all 4 tafenoquine dosages demonstrated significant protection against
P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95%
confidence interval [CI], 20%-43%); for 50 mg/week, 84% (95% CI, 75%-91%); for
100 mg/week, 87% (95% CI, 78%-93%); and for 200 mg/week, 86% (95% CI, 76%-92%).
The mefloquine dosage of 250 mg/week also demonstrated significant protection
against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%-93%).
There was little difference between study groups in the adverse events reported,
and there was no evidence of a relationship between tafenoquine dosage and
reports of physical complaints or the occurrence of abnormal laboratory
parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well
tolerated, and effective against P. falciparum infection in this study
population.