Summary of anti-malarial prophylactic efficacy of tafenoquine from three placebo-controlled studies of residents of malaria-endemic countries

Malaria Journal

Research

Geoffrey S. Dow¹  Brian Hetzell²  Jun Liu²  Gina Lin²  Sarah Thieling²  Douglas Tang³  Bryan Smith³  William F. McCarthy³ 

[1] 60° Pharmaceuticals LLC, 20036, Washington, DC, USA;PPD, Inc., 23230, Richmond, VA, USA;USAMMDA, 21702, Ft Detrick, MD, USA;

关键词: Malaria;    Prophylaxis;    Prophylactic efficacy;    Tafenoquine;    Mefloquine;    Malaria-endemic countries;   

DOI  :  10.1186/s12936-015-0991-x

 received in 2015-06-23, accepted in 2015-11-05,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundTafenoquine is a long half-life primaquine analog being developed for malaria prophylaxis. The US Army recently performed a unified analysis of efficacy in preparation for a regulatory submission, utilizing legacy data from three placebo-controlled studies conducted in the late 1990s and early 2000s. The subjects were residents of Africa who were naturally exposed to Plasmodium falciparum for 12–26 weeks.MethodsThe prophylactic efficacy of tafenoquine and mefloquine (included in some studies as a comparator) was calculated using incidence density among subjects who had completed the three-day loading doses of study drug, had at least one maintenance dose and had at least one blood smear assessed during the prophylactic period. The three placebo-controlled studies were analysed separately and then in two pooled analyses: one for tafenoquine versus placebo (three studies) and one for tafenoquine and mefloquine versus placebo (two studies).ResultsThe pooled protective efficacy (PE) of a tafenoquine regimen with three daily loading doses plus weekly maintenance at 200-mg for 10 weeks or longer (referred to as 200-mg weekly hereafter) relative to placebo in three placebo-controlled studies was 93.1 % [95 % confidence interval (CI) 89.1–95.6 %; total N = 492]. The pooled PEs of regimens of tafenoquine 200-mg weekly and mefloquine 250-mg weekly relative to placebo in two placebo-controlled studies (total N = 519) were 93.5 % (95 % CI 88.6–96.2 %) and 94.5 % (95 % CI 88.7–97.3 %), respectively. Three daily loading plus weekly maintenance doses of 50- and 100-mg, but not 25-mg, exhibited similar PEs. The PEs of tafenoquine regimens of a three-day loading dose at 400-mg with and without follow-up weekly maintenance doses at 400-mg were 93.7 % (95 % CI 85.4–97.3 %) and 81.0 % (95 % CI 66.8–89.1 %), respectively.ConclusionsTafenoquine provided the same level of prophylactic efficacy as mefloquine in residents of Africa. These data support the prophylactic efficacy of tafenoquine and mefloquine that has already been demonstrated in the intended malaria naive population.

【 授权许可】

CC BY   
© Dow et al. 2016