Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum.

Antimicrobial Agents and Chemotherapy
James S McCarthyPreetam Gandhi

Abstract

The spiroindolone cipargamin, a new antimalarial compound that inhibits Plasmodium ATP4, is currently in clinical development. This study aimed to characterize the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood-stage Plasmodium falciparum Eight subjects were intravenously inoculated with parasite-infected erythrocytes and received a single oral dose of 10 mg cipargamin 7 days later. Blood samples were collected to monitor the development and clearance of parasitemia and plasma cipargamin concentrations. Parasite regrowth was treated with piperaquine monotherapy to clear asexual parasites, while allowing gametocyte transmissibility to mosquitoes to be investigated. An initial rapid decrease in parasitemia occurred in all participants following cipargamin dosing, with a parasite clearance half-life of 3.99 h. As anticipated from the dose selected, parasite regrowth occurred in all 8 subjects 3 to 8 days after dosing and allowed the pharmacokinetic/pharmacodynamic relationship to be determined. Based on the limited data from the single subtherapeutic dose cohort, a MIC of 11.6 ng/ml and minimum parasiticidal concentration that achieves 90% of maximum effect of 23.5 ng/ml were estimated...Continue Reading

References

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Citations

Jul 28, 2021·Expert Opinion on Pharmacotherapy·Erik KoehneAndrea Kreidenweiss
Aug 20, 2021·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Esther K SchmittPreetam Gandhi

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Methods Mentioned

BETA
PCR

Clinical Trials Mentioned

NCT01860989
NCT03334747
NCT02543086

Software Mentioned

WinNonlin Pro
R
MonolixSuite

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