{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T10:21:32Z","timestamp":1774606892745,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,5,19]],"date-time":"2024-05-19T00:00:00Z","timestamp":1716076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The primary aim was to demonstrate bioequivalence between the 10\/20\u2009mg fixed\u2010dose combination (FDC) of macitentan\/tadalafil in a single tablet and the free combination of both drugs, and to evaluate the food effect on the 10\/20\u2009mg FDC in healthy participants. In this single\u2010center, randomized, open\u2010label, 3\u2010way crossover, single\u2010dose Phase 1 study in healthy adult participants, macitentan\/tadalafil was administered as a 10\/20\u2009mg FDC formulation and compared with the free combination of macitentan and tadalafil. The food effect on the FDC was also evaluated. Pharmacokinetic sampling (216\u2009h) was conducted. The 90% confidence intervals (CIs) for the geometric mean ratios of maximum observed plasma analyte concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) and area under the plasma analyte concentration\u2013time curves (AUCs) for Treatment A (FDC, fasted) versus C (free combination, fasted) were within bioequivalence limits demonstrating that the FDC formulation can be considered bioequivalent to the free combination. The 90% CIs for the geometric mean ratios of <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and AUC for Treatment B (FDC, fed) versus A (FDC, fasted) were contained within bioequivalence limits demonstrating that there was no food effect. The administration of the 10\/20\u2009mg FDC was generally safe and well tolerated in healthy participants. This study demonstrated bioequivalence between the FDC of macitentan\/tadalafil (10\/20\u2009mg) in a single tablet and the free combination of both drugs in healthy participants, and that the FDC can be taken without regard to food, similarly to the individual components. The FDC was generally safe and well tolerated.<\/jats:p>","DOI":"10.1002\/prp2.1202","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T05:23:25Z","timestamp":1716182605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bioequivalence and the food effect of macitentan\/tadalafil 10\/20 fixed\u2010dose combination tablets versus the use of single\u2010component tablets in healthy subjects"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1740-5704","authenticated-orcid":false,"given":"Jennifer Lynn","family":"Ford","sequence":"first","affiliation":[{"name":"Janssen Research &amp; Development  Spring House Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7266-3310","authenticated-orcid":false,"given":"Ahad","family":"Sabet","sequence":"additional","affiliation":[{"name":"ICON  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4833-1750","authenticated-orcid":false,"given":"Jaya","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development  Raritan New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6913-7285","authenticated-orcid":false,"given":"Hans","family":"Stieltjes","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9174-8118","authenticated-orcid":false,"given":"Daniel L.","family":"Chao","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development  Raritan New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8521-0108","authenticated-orcid":false,"given":"Navin","family":"Goyal","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development  Raritan New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7797-2615","authenticated-orcid":false,"given":"Denes","family":"Csonka","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals, A Janssen Pharmaceutical Company of Johnson &amp; Johnson  Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,19]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-5-343"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.031"},{"key":"e_1_2_17_4_1","unstructured":"Food and Drug Administration.Opsumit: United States Prescribing Information. Accessed March 25 2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/204410s017lbl.pdf"},{"key":"e_1_2_17_5_1","unstructured":"European Medicines Agency.Opsumit: Summary of Product Characteristics. Accessed March 25 2024.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/opsumit\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_17_6_1","unstructured":"Food and Drug Administration.Adcirca: United States Prescribing Information. Accessed March 25 2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/022332s009lbl.pdf"},{"key":"e_1_2_17_7_1","unstructured":"European Medicines Agency.Adcirca: Summary of Product Characteristics. Accessed March 25 2024.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/adcirca\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv317"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2019.11.041"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14347"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.846"},{"key":"e_1_2_17_12_1","unstructured":"European Medicines Agency.Evaluation of Medicines for Human Use CPMP. Guideline on the Investigation of Bioequivalence. CPMP\/QWP\/EWP\/1401\/98 Rev. 1.2010."},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02553.x"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1043-2"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0255-5"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.1202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T07:44:18Z","timestamp":1718351058000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.1202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,19]]},"references-count":16,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/prp2.1202"],"URL":"https:\/\/doi.org\/10.1002\/prp2.1202","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,19]]},"assertion":[{"value":"2024-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1202"}}