{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:31:50Z","timestamp":1790937110344,"version":"4.1.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004167","name":"Medicines for Malaria Venture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004167","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000200","name":"United States Agency for International Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000200","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000278","name":"Department for International Development, UK Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007843","name":"Direktoratet for Utviklingssamarbeid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009099","name":"Irish Aid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009022","name":"Newcrest Mining","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI109023"],"award-info":[{"award-number":["R01 AI109023"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics, and antimalarial activity of a tablet formulation of MMV390048.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A 2-part, phase 1 trial was conducted in healthy adults. Part 1 was a double-blind, randomized, placebo-controlled, single ascending dose study consisting of 3 cohorts (40, 80, 120 mg MMV390048). Part 2 was an open-label volunteer infection study using the Plasmodium falciparum induced blood-stage malaria model consisting of 2 cohorts (40 mg and 80 mg MMV390048).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty four subjects were enrolled in part 1 (n\u2005=\u20058 per cohort, randomized 3:1 MMV390048:placebo) and 15 subjects were enrolled in part 2 (40 mg [n = 7] and 80 mg [n = 8] cohorts). One subject was withdrawn from part 2 (80 mg cohort) before dosing and was not included in analyses. No serious or severe adverse events were attributed to MMV390048. The rate of parasite clearance was greater in subjects administered 80 mg compared to those administered 40 mg (clearance half-life 5.5 hours [95% confidence interval {CI}, 5.2\u20136.0 hours] vs 6.4 hours [95% CI, 6.0\u20136.9 hours]; P\u2005=\u2005.005). Pharmacokinetic\/pharmacodynamic modeling estimated a minimum inhibitory concentration of 83 ng\/mL and a minimal parasiticidal concentration that would achieve 90% of the maximum effect of 238 ng\/mL, and predicted that a single 120-mg dose would achieve an adequate clinical and parasitological response with 92% certainty.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The safety, pharmacokinetics, and pharmacodynamics of MMV390048 support its further development as a partner drug of a single-dose combination therapy for malaria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT02783820 (part 1); NCT02783833 (part 2).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaa368","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T11:21:54Z","timestamp":1585740114000},"page":"e657-e664","source":"Crossref","is-referenced-by-count":55,"title":["A Phase 1, Placebo-controlled, Randomized, Single Ascending Dose Study and a Volunteer Infection Study to Characterize the Safety, Pharmacokinetics, and Antimalarial Activity of the <i>Plasmodium<\/i> Phosphatidylinositol 4-Kinase Inhibitor MMV390048"],"prefix":"10.1093","volume":"71","author":[{"given":"James S","family":"McCarthy","sequence":"first","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Donini","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Chalon","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Woodford","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Marquart","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine A","family":"Collins","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix D","family":"Rozenberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Fidock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed H","family":"Cherkaoui-Rbati","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gobeau","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0769-9649","authenticated-orcid":false,"given":"J\u00f6rg J","family":"M\u00f6hrle","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"key":"2020121703251599500_CIT0001","doi-asserted-by":"crossref","first-page":"a025619","DOI":"10.1101\/cshperspect.a025619","article-title":"Antimalarial drug resistance: a threat to malaria elimination","volume":"7","author":"Menard","year":"2017","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2020121703251599500_CIT0002","doi-asserted-by":"crossref","DOI":"10.30875\/f309483f-en","volume-title":"World malaria report 2018","author":"World Health 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