{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:16:15Z","timestamp":1792444575079,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Omaveloxolone (SKYCLARYS\n                    <jats:sup>\u00ae<\/jats:sup>\n                    ) is approved for the treatment of Friedreich ataxia (FA) in patients aged \u226516 years in the United States and European Union (EU). The recommended dosage is 150 mg administered orally once daily as three 50\u2010mg capsules. However, some patients with FA may have oropharyngeal dysphagia or difficulty swallowing whole capsules; therefore, alternate method(s) of administration are needed. A Phase 1 clinical study in 32 healthy volunteers evaluated the relative bioavailability, safety, and tolerability of a single dose of omaveloxolone when capsule contents were sprinkled on and mixed in applesauce compared to when taken as intact capsules. Palatability when sprinkled on and mixed in applesauce was assessed with a questionnaire. After a single 150\u2010mg dose, the peak and overall exposures of omaveloxolone were similar irrespective of administration method, with the 90% CIs of the geometric least squares mean ratio (%) for maximum plasma concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ), AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    , and AUC\n                    <jats:sub>0\u2010\u221e<\/jats:sub>\n                    within the 80% to 125% reference intervals. Omaveloxolone was absorbed more slowly as intact capsules (median t\n                    <jats:sub>max<\/jats:sub>\n                    , 10 h) compared with sprinkled capsule contents over applesauce (median t\n                    <jats:sub>max<\/jats:sub>\n                    , 6 h). With chronic daily administration of omaveloxolone to treat FA, the 4\u2010h difference in t\n                    <jats:sub>max<\/jats:sub>\n                    is not considered clinically relevant. Sprinkled omaveloxolone capsule contents on applesauce were well tolerated, with acceptable palatability and no serious adverse events. Given the similar systemic exposure when capsules were swallowed whole, sprinkling omaveloxolone capsule contents on and mixing in applesauce is a feasible alternative method of administering omaveloxolone and has been included in both the United States and EU prescribing information.\n                  <\/jats:p>","DOI":"10.1002\/jcph.2482","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T01:44:01Z","timestamp":1717551841000},"page":"1304-1311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Relative Bioavailability of Omaveloxolone When Capsules Are Sprinkled Over and Mixed in Applesauce Compared With Administration as Intact Omaveloxolone Capsules: A Phase 1, Randomized, Open\u2010Label, Single\u2010Dose, Crossover Study in Healthy Adults"],"prefix":"10.1002","volume":"64","author":[{"given":"Scott M.","family":"Hynes","sequence":"first","affiliation":[{"name":"Biogen Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie","family":"Goldsberry","sequence":"additional","affiliation":[{"name":"Biogen Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick D.","family":"Henneghan","sequence":"additional","affiliation":[{"name":"Thermo Fisher Scientific Inc.  Bend Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Murai","sequence":"additional","affiliation":[{"name":"Biogen Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Shinde","sequence":"additional","affiliation":[{"name":"Reata Pharmaceuticals Inc.  Plano Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Wells","sequence":"additional","affiliation":[{"name":"Biogen Inc.  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Reata Pharmaceuticals Inc.;2024.https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/f1a1100e-8318-1596-e053-2995a90a533e\/spl-doc?hl=omaveloxolone"},{"key":"e_1_2_10_16_1","unstructured":"Skyclarys (omaveloxolone).Summary of product characteristics. Reata Ireland Limited;2024.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/skyclarys-epar-product-information_en.pdf"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.08.013"},{"issue":"15","key":"e_1_2_10_18_1","article-title":"Dysphagia in patients with Friedreich's ataxia (P6.342)","volume":"90","author":"Besharat A","year":"2018","journal-title":"Neurology"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29286"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25934"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.660"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010013\u20107208\u20104"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00455\u2010017\u20109804\u20104"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15463"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2019.05.003"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2482","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T01:34:54Z","timestamp":1727400894000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.2482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,4]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/jcph.2482"],"URL":"https:\/\/doi.org\/10.1002\/jcph.2482","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,4]]},"assertion":[{"value":"2024-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}