A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects

• Published in: Clinical pharmacology in drug development Vol. 14; no. 5; pp. 382 - 390
• Main Authors: Faison, Shamia L., Batonga, Joelle, Arumugham, Thangam, Bartkus, Angela, Morrison, Marion, Mullin, Mark J., Tippin, Tim, Naderer, Odin
• Format: Journal Article
• Language: English
• Published: United States 01.05.2025
• Subjects: Administration, Oral; Adult; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Area Under Curve; Biological Availability; Capsules; Cross-Over Studies; dordaviprone; dose escalation; Dose-Response Relationship, Drug; Double-Blind Method; Female; food effect; Food-Drug Interactions; Healthy Volunteers; Humans; Imidazoles; Male; Middle Aged; ONC201; pharmacokinetics; Pyridines; Pyridones - administration & dosage; Pyridones - adverse effects; Pyridones - pharmacokinetics; Pyrimidines; Therapeutic Equivalency; Young Adult; pharmacokinetics; dose escalation; food effect; ONC201; dordaviprone
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.1512

Dordaviprone (ONC201) is a novel, small molecule imipridone with antitumor effects in glioma patients. This study evaluated the pharmacokinetics and safety of dordaviprone following single escalating doses (Part A), as a capsule content mixed with applesauce or Gatorade (sports drink) [Part B1]), and with or without food [Part B2]. The most common treatment‐emergent adverse events pooled across study parts (Parts A, B1, and B2) were headache, dizziness, and headache, respectively; all were mild. Systemic dordaviprone exposure increased dose proportionally following administration of 125‐625 mg of dordaviprone. Following dordaviprone capsule contents sprinkled on applesauce or dissolved in sports drink, the geometric mean ratios, and 90% confidence intervals (CIs) of the dordaviprone area under the concentration versus time curve (AUC) fell within the bioequivalence (BE) limits of 80.00%‐125.00%; however, for Cmax the 90% CI lower limit (0.70) fell below BE limits when sprinkled on applesauce. The geometric mean ratios and 90% CIs of dordaviprone administered under fed versus fasted conditions fell within BE limits of 80.00%‐125.00% for the AUC, indicating no food effect on total exposure; however, maximum concentration (Cmax) (90% CI 0.55, 0.67) fell below BE limits.