NEW YORK (Reuters Health) – ZY19489, a novel triaminopyrimidine antimalarial compound, has successfully passed a first-in-human clinical trial, demonstrating promising safety, pharmacokinetics and antimalarial activity, according to a new report.
Conducted in 48 healthy adult volunteers in Australia, the study showed ZY-19489 was well tolerated up to the maximum dose tested of 1,500 mg, Dr. Bridget Barber with QIMR Berghofer Medical Research Institute in Brisbane, Australia, and colleagues report in The Lancet Infectious Diseases.
Single oral doses of the drug (200 mg, 300 mg, or 900 mg) led to “rapid” initial clearance of asexual blood-stage parasitemia, with a clearance half-life of roughly seven hours.
There was no evidence of in-vitro drug resistance in recrudescent parasite populations.
“Pharmacokinetic / pharmacodynamic analysis and dosing simulations predicted that a single dose of 1100 mg ZY-19489 would clear baseline parasitemia by a factor of 109,” the study team reports.
The study, which combined a single ascending dose study, pilot food-effect study, and volunteer-infection study enabled the rapid accrual of data to expedite clinical development, they note.
“Importantly, a new tool in the fight against malaria has successfully navigated phase 1,” write the authors of a linked commentary.
However, they say “challenges remain, including that a high dose of ZY-19489 from a single administration appears necessary due to the variable drug clearance.”
“The choice of a suitable partner drug will also be crucial to deliver a total curative regimen for patients. The acceptability of the total drug dose and formulation requirements in a future drug combination will be key to its success; thus, it will be interesting to see if a two-dose or three-dose regimen is explored going forwards,” the commentary writers add.
The study was funded by Cadila Healthcare and the Medicines for Malaria Venture (MMV). Several authors are employed by Cadila Healthcare and MMV.
SOURCE: https://bit.ly/3sVo8Zh and https://bit.ly/35GOju1 Lancet Infectious Diseases, online March 2, 2022.
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