{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:19:07Z","timestamp":1784330347219,"version":"3.55.0"},"reference-count":13,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T00:00:00Z","timestamp":1580688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009754","name":"Galderma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009754","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":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trifarotene is a new drug with retinoic acid receptor activity and selectivity for retinoic acid receptor\u2010\u03b3. The reported studies aimed at assessing the clinical pharmacology and safety of trifarotene. The clinical pharmacology of topical trifarotene up to 100\u00a0\u00b5g\/g was extensively investigated through 2\u00a0maximal usage pharmacokinetic trials (MUsT) conducted in adult (\u226518\u00a0years) and pediatric patients (9\u201017\u00a0years) with moderate to severe acne and two studies conducted in healthy volunteers: 1 thorough QT<jats:sub>C<\/jats:sub> study and 1 drug\u2010drug interaction study with concomitantly administered oral levonorgestrel (0.15 mg)\/ethinyl estradiol (0.03 mg). Safety assessments included adverse event reporting and assessment of erythema, scaling, dryness, and stinging\/burning using a scale from 0 = none to 4 = severe, as well as the evaluation of the systemic safety of trifarotene through routine laboratory testing. Systemic absorption of trifarotene was generally unquantifiable in the target population, especially when applied at 50\u00a0\u00b5g\/g. QT<jats:sub>C<\/jats:sub> investigations did not show any risk of cardiovascular health issues; trifarotene did not reduce the systemic exposure to oral contraceptives such as levonorgestrel\/ethinyl estradiol. Safety analyses did not show local or systemic safety concerns with trifarotene up 100\u00a0\u00b5g\/g, a dose twice as high as the intended market dose. Results showed that trifarotene 50\u00a0\u00b5g\/g cream is well tolerated and safe, even when applied under maximized conditions in adults and pediatric acne patients presenting with severe acne. Daily use of trifarotene 50\u00a0\u00b5g\/g cream was not associated with cardiovascular effects and did not result in drug\u2010drug interaction in women of childbearing potential using oral contraception.<\/jats:p>","DOI":"10.1002\/jcph.1566","type":"journal-article","created":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T07:21:05Z","timestamp":1580800865000},"page":"660-668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Clinical Pharmacology and Safety of Trifarotene, a First\u2010in\u2010Class RAR\u03b3\u2010Selective Topical Retinoid"],"prefix":"10.1002","volume":"60","author":[{"given":"Nathalie","family":"Wagner","sequence":"first","affiliation":[{"name":"Galderma Research and Development LLC  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Benkali","sequence":"additional","affiliation":[{"name":"Galderma Research and Development  Sophia Antipolis France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ali\u00f3 S\u00e1enz","sequence":"additional","affiliation":[{"name":"Galderma Research and Development LLC  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Poncet","sequence":"additional","affiliation":[{"name":"Galderma Research and Development  Sophia Antipolis France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Graeber","sequence":"additional","affiliation":[{"name":"Galderma Research and Development LLC  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-015-0127-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14374"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-0490B"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16719"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/2168479014539157"},{"key":"e_1_2_10_7_1","unstructured":"FDA guidance: Maximal Usage Trials for Topically Applied Active Ingredients Being Considered for Inclusion in an Over\u2010The \u2010 Counter Monograph: Study Elements and Considerations.https:\/\/www.fda.gov\/media\/125080\/downloadAccessed May 2019."},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12168"},{"key":"e_1_2_10_9_1","unstructured":"European Medicines Agency. Guideline on the investigation of drug interactions; CPMP\/EWP\/560\/95\/Rev. 1 Corr. 2**; Committee for Human Medicinal Products (CHMP).https:\/\/www.ema.europa.eu\/documents\/scientific-guideline\/guideline-investigation-drug-interactions_en.pdf. Published June 21 2012. Accessed April 28 2019."},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.026997"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-014-0215-8"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010381498"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.111482"},{"key":"e_1_2_10_14_1","unstructured":"International Conference for Harmonisation. E14 Implementation Working Group ICH E14 Guideline: The clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs questions & answers (R3). Published December 10 2015. Accessed April 28 2019."}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1566","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1566","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1566","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1566","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T02:13:21Z","timestamp":1692756801000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,3]]},"references-count":13,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/jcph.1566"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1566","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,3]]},"assertion":[{"value":"2019-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}