{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:36:25Z","timestamp":1790213785813,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peposertib is an orally administered inhibitor of DNA\u2010dependent protein kinase. We evaluated the effect of food on its pharmacokinetics, and examined the pharmacokinetics of an oral suspension (OS) of disintegrated tablets, in a phase I, open\u2010label, crossover three\u2010period study (NCT04702698). Twelve healthy volunteers were randomized to one of six treatment sequences. They received a single dose of peposertib 100\u2009mg as film\u2010coated tablets under fasted or fed conditions (\u201ctablet fasted\u201d or \u201ctablet fed\u201d) or as an OS under fasted conditions (\u201cOS fasted\u201d), with washout between treatments. Using healthy volunteers was possible because, despite its mechanism of action being suppression of DNA repair, peposertib has shown no genotoxic effect in animals. A mild food effect was observed with peposertib tablets. Fed\u2010to\u2010fasted ratios were: area under the curve from time 0 to time <jats:italic>t<\/jats:italic> (AUC<jats:sub>0\u2013t<\/jats:sub>), 123.81% (90% confidence interval [CI]: 108.04, 141.87%); AUC from zero to infinity (AUC<jats:sub>0\u2013\u221e<\/jats:sub>), 110.28% (90% CI 100.71, 120.77%); and maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) 104.47% (90% CI: 79.15, 137.90%). <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> was delayed under fed conditions (median time to maximum concentration [<jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub>] was 3.5\u2009h [tablet fed] vs. 1\u2009h [tablet fasted]). OS\u2010to\u2010tablet (fasted) ratios were: AUC<jats:sub>0\u2013t<\/jats:sub>, 124.83% (90% CI: 111.50%, 139.76%); AUC<jats:sub>0\u2013\u221e<\/jats:sub>, 119.05% (90% CI: 104.47, 135.67%); and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> 173.29% (90% CI: 135.78, 221.16%). Median <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> was 0.5\u2009h (OS fasted) versus 1\u2009h (tablet). All treatments were well\u2010tolerated in healthy volunteers. Peposertib tablets can be taken with or without food; if combined with chemotherapy or radiotherapy, the delay in <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> must be considered to optimize the chemo\u2010 or radiosensitizing effect. The peposertib OS form represents an alternative route of administration in patients with specific cancers causing dysphagia. However, the OS form should be part of future dose optimization strategies in relevant settings.<\/jats:p>","DOI":"10.1111\/cts.13657","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T07:57:40Z","timestamp":1698739060000},"page":"2628-2639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phase I crossover study of DNA\u2010protein kinase inhibitor peposertib in healthy volunteers: Effect of food and pharmacokinetics of an oral suspension"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7424-2588","authenticated-orcid":false,"given":"Andreas","family":"Becker","sequence":"first","affiliation":[{"name":"The healthcare business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Krebs\u2010Brown","sequence":"additional","affiliation":[{"name":"The healthcare business of Merck KGaA  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