DSM265 400 mg clears asexual stage parasites but not mature gametocytes from the blood of healthy subjects experimentally infected with Plasmodium falciparum.

DSM265 400 mg clears asexual stage parasites but not mature gametocytes from the blood of healthy subjects experimentally infected with Plasmodium falciparum. Antimicrob Agents Chemother. 2019 Mar 11;: Authors: Collins KA, Rückle T, Elliott S, Marquart L, Ballard E, Chalon S, Griffin P, Möhrle JJ, McCarthy JS Abstract DSM265 is a novel antimalarial drug in clinical development that acts as a selective inhibitor of Plasmodium dihydroorotate dehydrogenase. In a previous Phase 1b study, a single 150 mg dose of DSM265 showed partial efficacy against experimentally induced blood-stage P. falciparum malaria (IBSM). PK/PD modeling predicted a human efficacious dose of 340 mg. The primary objectives of the current study were to determine the safety and efficacy of a single oral 400 mg dose of DSM265 against P. falciparum in the IBSM model. Eight healthy participants were inoculated intravenously with 2,800 parasites and treated with DSM265 7 days later. Unexpectedly, one participant did not develop parasitemia during the study. All other participants developed parasitemia, with complete clearance of asexual parasites following DSM265 treatment. All seven subjects also became gametocytemic. The secondary objectives were to investigate the gametocytocidal and transmission-blocking activity of a second 400 mg dose of DSM265, which was administered 23 days after inoculation. Gametocytes were not cleared by the second dose of DSM265, and transm...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research