{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:34:58Z","timestamp":1783658098144,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"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\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["19\u2010BMGF\u2010006"],"award-info":[{"award-number":["19\u2010BMGF\u2010006"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the safety, tolerability and pharmacokinetics in healthy participants of orally administered MMV367 (GSK3772701), a novel antimalarial interfering with <jats:italic>Plasmodium falciparum<\/jats:italic> acyl coenzyme A synthetase 10\/11 function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This first\u2010in\u2010human study enrolled 47 healthy male and female participants. Part 1 was a randomised, double\u2010blind, placebo\u2010controlled study in which four sequential fasted cohorts received MMV367 single ascending doses (100, 300, 750 and 1500\u2009mg) or placebo (six active, two placebo per cohort). Part 2 was a randomised, open\u2010label crossover (fed\u2010fasted) pilot food\u2010effect study of MMV367 440\u2009mg (n\u2009=\u20098). In Part 3 MMV367 400\u2009mg was administered once daily for 3\u00a0days in a single cohort (six active, two placebo).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment\u2010emergent adverse events (TEAEs) occurred in 36.8% (14\/38) of participants receiving MMV367 <jats:italic>vs<\/jats:italic> 44.4% (4\/9) with placebo. There were two MMV367\u2010related TEAEs, and no serious or severe TEAEs or clinically relevant changes in electrocardiograms, vital signs or laboratory tests. In Part 1 (fasted), maximum plasma concentrations occurred between 2.0 and 5.0\u00a0h post dose, with a geometric mean half\u2010life of 16.5\u201018.4\u00a0h. Approximate dose proportionality was demonstrated across the dose range (100\u20101500\u2009mg). In Part 2, MMV367 relative bioavailability (fed <jats:italic>vs<\/jats:italic> fasted) was 161.4% (90% confidence interval 148.3, 175.6) for maximum observed concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>), 130.4% (122.2, 139.1) for the area under the curve (AUC) until the last measurable concentration and 132.9% (124.1, 142.3) for AUC extrapolated to infinity. In Part 3, geometric mean day 1:3 exposure ratios (geometric co\u2010efficient of variability) were 1.9 (4.9%) for <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and 2.1 (7.7%) for the AUC for the defined interval between doses after once\u2010daily dosing for 3\u00a0days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MMV367 demonstrated acceptable safety, tolerability and pharmacokinetic profiles supporting further development as an antimalarial drug.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bcp.70000","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:15:38Z","timestamp":1739751338000},"page":"1821-1833","source":"Crossref","is-referenced-by-count":4,"title":["First\u2010in\u2010human safety, tolerability, pharmacokinetics and pilot food\u2010effect study of the candidate antimalarial compound MMV367"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-2676","authenticated-orcid":false,"given":"Andrea","family":"Kuemmerle","sequence":"first","affiliation":[{"name":"MMV Medicines for Malaria Venture  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6683-7450","authenticated-orcid":false,"given":"Nand","family":"Singh","sequence":"additional","affiliation":[{"name":"Quotient Sciences  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2704-1560","authenticated-orcid":false,"given":"Denis","family":"Gossen","sequence":"additional","affiliation":[{"name":"Mangareva SRL, Kraainem  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7426-0304","authenticated-orcid":false,"given":"Annick","family":"Janin","sequence":"additional","affiliation":[{"name":"AKJ Consulting, Divonne  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5437-5743","authenticated-orcid":false,"given":"Raman","family":"Sharma","sequence":"additional","affiliation":[{"name":"GSK, Clinical Pharmacology and Simulation, R&amp;D  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7239-0461","authenticated-orcid":false,"given":"Anthony","family":"Cahn","sequence":"additional","affiliation":[{"name":"GSK, Global Health Medicines, R&amp;D  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-1290","authenticated-orcid":false,"given":"Rachel A.","family":"Gibson","sequence":"additional","affiliation":[{"name":"GSK, Global Health Medicines, R&amp;D  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7028-7697","authenticated-orcid":false,"given":"Somasekhara R.","family":"Menakuru","sequence":"additional","affiliation":[{"name":"Quotient Sciences  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9258-9330","authenticated-orcid":false,"given":"Erin","family":"Lambourne","sequence":"additional","affiliation":[{"name":"Quotient Sciences  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7132-1859","authenticated-orcid":false,"given":"Tom","family":"Dove","sequence":"additional","affiliation":[{"name":"Quotient Sciences  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-2882","authenticated-orcid":false,"given":"Francisco\u2010Javier","family":"Gamo","sequence":"additional","affiliation":[{"name":"GSK, Global Health Medicines, R&amp;D  Tres Cantos Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-5211","authenticated-orcid":false,"given":"Laura","family":"Sanz","sequence":"additional","affiliation":[{"name":"GSK, Global Health Medicines, R&amp;D  Tres Cantos Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-2113","authenticated-orcid":false,"given":"Benoit","family":"Bestgen","sequence":"additional","affiliation":[{"name":"MMV Medicines for Malaria Venture  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-1851","authenticated-orcid":false,"given":"Stephan","family":"Chalon","sequence":"additional","affiliation":[{"name":"MMV Medicines for Malaria Venture  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,16]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"World Health Organization.World malaria report. 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