Efficacy of a Novel Sublingual Spray Formulation of Artemether in African Children with Plasmodium falciparum Malaria

Abstract

ABSTRACT The efficacy of sublingual artemether (ArTiMist) was investigated in two studies. In study 1, 31 children were randomized to sublingual artemether ( n = 16) or intravenous (i.v.) quinine ( n = 15). In study 2, 151 children were randomized to sublingual artemether ( n = 77) or i.v. quinine ( n = 74). For both studies, patients weighed between 5 and 15 kg and had either severe or complicated malaria based on WHO criteria, or they had uncomplicated malaria but were unable to tolerate oral medication as a result of nausea, vomiting, or diarrhea. Patients received either 3 mg/kg of body weight of sublingual artemether or a loading dose of 20 mg/kg of i.v. quinine followed by 10 mg/kg every 8 h i.v. thereafter. The primary endpoint was parasitological success, defined as a reduction in parasite count of ≥90% of that at baseline at 24 h after the first dose. Other endpoints based on parasite clearance and clinical response were evaluated. In study 1, there were parasitological success rates of 93.3% (14/15) and 66.7% (10/15) for the sublingual artemether and quinine treatments, respectively. In study 2, 94.3% (66/70) of the ArTiMist-treated patients and 39.4% (28/71) of the quinine-treated patients had parasitological success ( P < 0.0001). Indicators of parasite clearance (parasite clearance time [PCT], time for parasite count to fall by 50% [PCT 50 ], time for parasite count to fall by 90% [PCT 90 ], and percent reduction in parasitemia from baseline at 24 h [PRR 24 ]) were significantly superior for children treated with sublingual artemether compared to those treated with i.v. quinine. There were no differences between treatments for the clinical endpoints, such as fever clearance time. The local tolerability of sublingual artemether was good. Sublingual artemether leads to rapid parasite clearance and clinical recovery. (Studies 1 and 2 are registered at ClinicalTrials.gov under registration numbers NCT01047436 and NCT01258049, respectively.)