Antimalarial activity of KAF156 in falciparum and vivax malaria
| Autor: | Kittiphum Chuthasmit, Ming S. Cheung, François Nosten, Nicholas J. White, F. Joel Leong, Daniela Wieser, Baldur Magnusson, Peter Pertel, Tran T. Duong, Thierry T. Diagana, Aung Pyae Phyo, Rong Zhao, Marc Sultan, Chirapong Uthaisin, Yiyan Feng, Borimas Hanboonkunupakarn, Sasithon Pukrittayakamee, Podjanee Jittamala, Ruobing Li, Xiaolei Xun |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Fever 030106 microbiology Plasmodium vivax Plasmodium falciparum Administration Oral Parasite load Parasite Load Piperazines Article 03 medical and health sciences Antimalarials Young Adult Interquartile range Internal medicine parasitic diseases medicine Malaria Vivax Humans Antimalarial Agent Malaria Falciparum biology business.industry Imidazoles General Medicine Middle Aged biology.organism_classification medicine.disease Regimen 030104 developmental biology Cohort Female business Malaria |
| Popis: | KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites.We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg).Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts.KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323 .). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|