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Adverse events associated with antifibrotics can be a barrier to adoption and persistence in patients with interstitial lung diseases, most of whom are not on standard\u2010of\u2010care therapy. LYT\u2010100 is designed to have a differentiated pharmacokinetic (PK) profile from pirfenidone and could offer a differentiated safety profile compared to current standard\u2010of\u2010care drugs while retaining the biochemical potency and specificity of pirfenidone. We conducted a phase 1b study to ascertain the safety, tolerability, steady\u2010state PK profile, and food effect of LYT\u2010100. This was a 2\u2010part study. Part 1 assessed multiple ascending doses of LYT\u2010100 from 100, 250, 500, 750, and 1000 mg twice daily given over 5 days without titration. Part 2 assessed the effects of fed vs fasting conditions on the PK profile of a single 500\u2010mg dose of LYT\u2010100. All doses up to 1000 mg were well tolerated, with adverse events being mild and transient. Exposure was slightly lower in the fed condition. LYT\u2010100 was well tolerated and has a dose\u2010proportional PK profile. The ratio of parent to major metabolite concentration was higher than reported with pirfenidone, which is consistent with an effect of deuteration on metabolism. No maximum tolerated dose was identified up to 1000 mg twice\u2010daily dosing. These results support further clinical development of LYT\u2010100, particularly considering the adverse event profile of current standard\u2010of\u2010care drugs.<\/jats:p>","DOI":"10.1002\/cpdd.1040","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T10:18:52Z","timestamp":1636971532000},"page":"220-234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Randomized Phase 1 Evaluation of Deupirfenidone, a Novel Deuterium\u2010Containing Drug Candidate for Interstitial Lung Disease and Other Inflammatory and Fibrotic Diseases"],"prefix":"10.1002","volume":"11","author":[{"given":"Michael C.","family":"Chen","sequence":"first","affiliation":[{"name":"PureTech Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Korth","sequence":"additional","affiliation":[{"name":"PureTech Health  Boston Massachusetts 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