Phase I crossover study of DNA‐protein kinase inhibitor peposertib in healthy volunteers: Effect of food and pharmacokinetics of an oral suspension

• DOI: 10.1111/cts.13657
• Publication Date: 2023-10-31T07:57:40Z
• Authors: Andreas Becker; Axel Krebs‐Brown; Claudia Vetter; Tanja Reuter; Almudena Rodrigue...; Xiaoli You; Michael Lissy
• Keywords: Crossover study; Washout

Abstract Peposertib is an orally administered inhibitor of DNA‐dependent protein kinase. We evaluated the effect food on its pharmacokinetics, and examined pharmacokinetics oral suspension (OS) disintegrated tablets, in a phase I, open‐label, crossover three‐period study (NCT04702698). Twelve healthy volunteers were randomized to one six treatment sequences. They received single dose peposertib 100 mg as film‐coated tablets under fasted or fed conditions (“tablet fasted” “tablet fed”) OS (“OS fasted”), with washout between treatments. Using was possible because, despite mechanism action being suppression DNA repair, has shown no genotoxic animals. A mild observed tablets. Fed‐to‐fasted ratios were: area curve from time 0 t (AUC 0–t ), 123.81% (90% confidence interval [CI]: 108.04, 141.87%); AUC zero infinity 0–∞ 110.28% CI 100.71, 120.77%); maximum concentration ( C max ) 104.47% CI: 79.15, 137.90%). delayed (median [ T ] 3.5 h [tablet fed] vs. 1 fasted]). OS‐to‐tablet (fasted) , 124.83% 111.50%, 139.76%); 119.05% 104.47, 135.67%); 173.29% 135.78, 221.16%). Median 0.5 (OS fasted) versus (tablet). All treatments well‐tolerated volunteers. can be taken without food; if combined chemotherapy radiotherapy, delay must considered optimize chemo‐ radiosensitizing effect. The form represents alternative route administration patients specific cancers causing dysphagia. However, should part future optimization strategies relevant settings.