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This pilot study assessed whether the relative bioavailability (F<jats:sub>rel<\/jats:sub>) of ATV, PG, and the primary PG metabolite cycloguanil (CG) following a single oral dose in the fed state of <jats:italic>Atoguanil<\/jats:italic> was similar to <jats:italic>Malarone<\/jats:italic> despite a 50% lower ATV dose. This open-label, single-dose, randomized 2-period, 2-treatment, balanced crossover study was conducted between 17th November 2021 and 18th March 2022. Eligible participants (aged 18\u201355 years) were randomized (1:1) in period 1 to <jats:italic>Atoguanil<\/jats:italic> (ATV\/PG 500\/348 mg) or <jats:italic>Malarone<\/jats:italic> (ATV\/PG hydrochloride 1000\/400 mg) administered following a high-fat, high caloric meal. After a 24-day washout period, participants crossed treatment arms. For the doses tested, F<jats:sub>rel<\/jats:sub> was assumed similar if 90%CIs were between 80 and 125% for the geometric mean ratio of the least square mean differences for each exposure parameter. In 15 evaluable participants, F<jats:sub>rel<\/jats:sub> was similar for ATV C<jats:sub>max<\/jats:sub> (93.6% [90%CI 83.6, 104.9]) but not AUC<jats:sub>0-inf<\/jats:sub> (77.8% [67.4, 89.8]), for PG AUC<jats:sub>0-inf<\/jats:sub> (95.6% [92.1, 99.2]) but not C<jats:sub>max<\/jats:sub> (82.4% [75.8, 89.5]), and for both CG C<jats:sub>max<\/jats:sub> (100.8% [95.0, 107.0]) and AUC<jats:sub>0-inf<\/jats:sub> (102.9% [98.4, 107.7]). Nine adverse events occurred; all were of mild severity and not considered treatment related. At the doses tested, ATV F<jats:sub>rel<\/jats:sub> was lower following <jats:italic>Atoguanil<\/jats:italic> versus <jats:italic>Malarone<\/jats:italic> based on AUC<jats:sub>0-inf<\/jats:sub>, though when adjusted for dose F<jats:sub>rel<\/jats:sub> increased by 156%. Both drugs were well tolerated with no safety concerns. ClinicalTrials.gov: NCT04866602 (April 26th, 2021)<\/jats:p>","DOI":"10.1007\/s00210-024-03245-x","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T18:08:15Z","timestamp":1719338895000},"page":"9823-9832","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A randomized, open-label two-period crossover pilot study to evaluate the relative bioavailability in the fed state of atovaquone-proguanil (Atoguanil\u2122) versus atovaquone-proguanil hydrochloride (Malarone\u00ae) in healthy adult participants"],"prefix":"10.1007","volume":"397","author":[{"given":"Andrea","family":"Kuemmerle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Gossen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Marx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Lorch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Szramowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharmendra","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satinder","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanu","family":"Ramachandruni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byju","family":"Thankachen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swapnil","family":"Kore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam El","family":"Gaaloul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Borghini-Fuhrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-1851","authenticated-orcid":false,"given":"Stephan","family":"Chalon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"issue":"2","key":"3245_CR1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.4314\/gmj.v56i2.2","volume":"56","author":"MR Adjei","year":"2022","unstructured":"Adjei MR, Kubio C, Buamah M, Sarfo A, Suuri T, Ibrahim S, Sadiq A, Abubakari II, Baafi JV (2022) Effectiveness of seasonal malaria chemoprevention in reducing under-five malaria morbidity and mortality in the Savannah Region. 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The study protocol including one amendment were reviewed and approved by the London Bridge Research Ethics Committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"HR, MEG, IB-F, and SC are employees of MMV. AK was employed at Medicines for Malaria Venture (MMV) when the study was designed and conducted and is a current employee of Novartis, Biomedical Research, Basel, Switzerland; the content of this paper is the responsibility of the individual authors and neither the study nor this publication is associated with Novartis, Biomedical Research. DG is the owner and director of Mangareva SRL, which received financial support from MMV to review and interpret the study results. MM is an employee of ICON Clinical Research, Langen, Germany, which received financial support from MMV to monitor the study. UL is an employee of Richmond Pharmacology Ltd, which received financial support from MMV to conduct the study. MS is an employee of PharmaKinetic Ltd which received financial support from MMV to perform the pharmacokinetic analysis. AK, DS, BT, and SK are employees of IPCA Laboratories Limited, Mumbai, India. SS was employed at IPCA Laboratories Limited when the study was designed and conducted and is a current employee of Aragen Life Sciences, Hyderabad, India; the content of this paper is the responsibility of the individual authors and neither the study nor this publication is associated with Aragen Life Sciences.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third-party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit .","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Open access"}}]}}