Randomized, Double-Blind, Placebo-Controlled Studies to Assess Safety and Prophylactic Efficacy of Naphthoquine-Azithromycin Combination for Malaria Prophylaxis in Southeast Asia.
New prophylactic drugs against malaria infections are urgently needed. We conducted randomized, double-blind, placebo-controlled, phase 2 trials of a new antimalarial drug combination, naphthoquine-azithromycin (NQAZ), to determine its safety and protective efficacy in a low-endemicity area of Southeast Asia. In the first trial, 127 healthy volunteers were randomized to receive two single doses of either 400 mg of NQAZ (200 mg of each drug), 800 mg of NQAZ (400 mg of each drug), or placebo on day 0 and day 30. Weekly follow-ups were performed for 2 months, and physical and clinical laboratory exams were done during the second and eighth week. Both drug regimens were well tolerated, without any serious adverse events. Four adverse events (transient and slight elevations of serum transaminase concentrations) were found only in the two drug-treated groups and thus might be drug-related. In the second trial, 353 volunteer villagers were randomized into the same three groups as in the first trial, and malaria infections were followed for a month. For the intention-to-treat analysis, both regimens offered greater than 90% prophylactic efficacies against all malaria infections. When the analysis was done according to parasite species, 400 mg and 800 mg NQAZ provided 81.63 and 90.59% prophylactic efficacies, respectively, against Plasmodium falciparum infections, whereas both offered 100% prophylactic efficacy against Plasmodium vivax and Plasmodium ovale These trials showed that NQAZ had a good safety profile, and monthly single doses of 400 mg or 800 mg for adults offered excellent prophylaxis against malaria infections, especially the two relapsing species.
['Yang|Henglin|H|', 'Wang|Jingyan|J|', 'Liu|Hui|H|', 'Li|Xingliang|X|', 'Nie|Renhua|R|', 'Li|Chunfu|C|', 'Wang|Hengye|H|', 'Wang|Qinghu|Q|', 'Cao|Yaming|Y|', 'Cui|Liwang|L|0000-0002-8338-1974']
D015057:1-Naphthylamine D000293:Adolescent D000328:Adult D000634:Aminoquinolines D000962:Antimalarials D017963:Azithromycin D018890:Chemoprevention D002648:Child D002681:China D004311:Double-Blind Method D004359:Drug Therapy, Combination D005260:Female D064368:Healthy Volunteers D006801:Humans D016778:Malaria, Falciparum D016780:Malaria, Vivax D008297:Male D008875:Middle Aged D010963:Plasmodium falciparum D041122:Plasmodium ovale D010966:Plasmodium vivax D055815:Young Adult
malaria prophylaxis drug combination safety profile clinical efficacy