{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:18:54Z","timestamp":1788931134878,"version":"build-2803163510"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T00:00:00Z","timestamp":1727568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"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","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The novel antimalarial ganaplacide combined with lumefantrine solid dispersion formulation (LUM\u2010SDF) was effective and well tolerated in the treatment of uncomplicated falciparum malaria in adults, adolescents, and children in a multinational, prospective, randomized, active\u2010controlled Phase II study conducted between August 2017 and June 2021 (EudraCT 2020\u2010003284\u201025, Clinicaltrials.gov NCT03167242). Pharmacokinetic data from that study are reported here.<\/jats:p>\n                  <jats:p>\n                    The trial comprised three parts: a run\u2010in part in 12 adult\/adolescent patients treated with a single dose of ganaplacide 200 mg plus LUM\u2010SDF 960 mg assessed potential pharmacokinetic (PK) interactions between ganaplacide and lumefantrine; in Part A, adult\/adolescent patients received one of the six ganaplacide\u2010LUM\u2010SDF regimens or artemether\u2010lumefantrine; and in Part B, three dose regimens identified in Part A, and artemether\u2010lumefantrine, were assessed in children aged 2 to &lt;12 years, with body weight \u226510 kg. A rich blood sampling schedule was used for all 12 patients in the PK run\u2010in part and a subset of patients (N = 32) in Part A, with sparse sampling for remaining patients in Parts A (N = 275) and B (N = 159). Drug concentrations were determined by a validated protein precipitation and reverse phase liquid chromatography with tandem mass spectrometry detection method. Parameters including AUC\n                    <jats:sub>inf<\/jats:sub>\n                    , AUC\n                    <jats:sub>last<\/jats:sub>\n                    , AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    ,\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max,<\/jats:sub>\n                    and t\n                    <jats:sub>max<\/jats:sub>\n                    were reported where possible, using non\u2010compartmental analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    In the PK run\u2010in part, there was no notable increase in ganaplacide or lumefantrine exposure when co\u2010administered. In Parts A and B, ganaplacide exposures increased with dose, but lumefantrine exposure was numerically under dose\u2010proportional. Lumefantrine exposure was higher with ganaplacide\u2010LUM\u2010SDF than with artemether\u2010lumefantrine, although high variability was observed. Ganaplacide and lumefantrine exposures (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u201024 h<\/jats:sub>\n                    ) were comparable across age and body weight groups. Drug exposures needed for efficacy were achieved using the dose regimen 400 mg ganaplacide plus lumefantrine 960 mg once daily for 3 days under fasted conditions.\n                  <\/jats:p>","DOI":"10.1002\/jcph.6138","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T02:46:59Z","timestamp":1727664419000},"page":"179-189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with\n                    <i>Plasmodium falciparum<\/i>\n                    Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study"],"prefix":"10.1002","volume":"65","author":[{"given":"Ramachandra","family":"Sangana","sequence":"first","affiliation":[{"name":"PK Sciences, Biomedical Research, Novartis  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhards","family":"Ogutu","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research Kenya Medical Research Institute Kisumu, Kenya and CREATES, Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adoke","family":"Yeka","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration  Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Kusemererwa","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Resea rch Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit  Entebbe Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halidou","family":"Tinto","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Science de la Sant\u00e9 \u2010 Unit\u00e9 de Recherche Clinique de Nanoro (IRSS\u2010URCN)  Nanoro Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre Offianan","family":"Toure","sequence":"additional","affiliation":[{"name":"Department of Parasitology\u2010Mycology Institut Pasteur de C\u00f4te d'Ivoire  Abidjan C\u00f4te d'Ivoire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afizi","family":"Kibuuka","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration (IDRC)  Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moussa","family":"Lingani","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Science de la Sant\u00e9 \u2010 Unit\u00e9 de Recherche Clinique de Nanoro (IRSS\u2010URCN)  Nanoro Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Ch\u00f3kw\u00e8 Health Research and Training Center\/Centro de 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