Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers
Rattachement africain : Afrique du Sud, ch, au. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
induced blood-stage malaria (IBSM) model. Due to the high pharmacokinetic variability with the powder-in-bottle formulation used in both of these studies, a third study was undertaken to select a tablet formulation of MMV390048 to take forward into future studies. MMV390048 was generally well tolerated when administered as a single oral dose up to 120 mg, with rapid absorption and a long elimination half-life. Twelve adverse events were considered to be potentially related to MMV390048 in the first-in-human study but with no obvious correlation between these and MMV390048 dose or exposure. Although antimalarial activity was evident in the IBSM study, rapid recrudescence occurred in most subjects after treatment with 20 mg MMV390048, a dose expected to be subtherapeutic. Reformulation of MMV390048 into two tablet formulations (tartaric acid and Syloid) resulted in significantly reduced intersubject pharmacokinetic variability. Overall, the results of this study suggest that MMV390048 is well tolerated in humans, and the pharmacokinetic properties of the compound indicate that it has the potential to be used for antimalarial prophylaxis or inclusion in a single-dose cure. MMV390048 is currently being tested in a phase 2a study in Ethiopian adults with acute, uncomplicated falciparum or vivax malaria monoinfection. (The three clinical trials described here were each registered with ClinicalTrials.gov as follows: first-in-human study, registration no. NCT02230579; IBSM study, registration no. NCT02281344; and formulation optimization study, registration no. NCT02554799.).
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel <i>Plasmodium</i> Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers
- Date Crossref
- 24/03/2020
- Éditeur
- American Society for Microbiology
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Cape Town Division of Clinical Pharmacology University of Cape Town, Afrique du Sud (code pays fourni par la source)Université ou école supérieure
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Medicines for Malaria Venture pays non établi dans la noticeOrganisation à but non lucratif
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QIMR Berghofer Medical Research Institute pays non établi dans la noticeStructure de recherche
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South African Medical Research Council Afrique du Sud (code pays fourni par la source)Institution
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HJ-Clinical Trial Consultancy Afrique du Sud (pays nommé en fin d’affiliation)Établissement de santé
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PTx Solutions Limited pays non établi dans la noticeInstitution
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Richmond Pharmacology pays non établi dans la noticeInstitution
Division of Clinical Pharmacology — University of Cape Town (University of Cape Town, Afrique du Sud), Medicines for Malaria Venture et QIMR Berghofer Medical Research Institute, avec 4 autres affiliations. Pays d’affiliation : Afrique du Sud.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.