Evaluation of the Effect of Food on the Pharmacokinetics of SHR6390, An Oral CDK4/6 Inhibitor, in Healthy Volunteers

• Published in: Drugs in R&D 2022-06, Vol.22 (2), p.175-182
• Main Authors: Liu, Yan-ping, Hu, Ming-hui, Lin, Ping-ping, Li, Ting, Liu, Shu-qin, Wang, Yu-ya, Li, Shao-rong, Li, Xiang-kun, Wang, Chen-jing, Cao, Yu
• Format: Article
• Language: English
• Subjects: Administration, Oral; Area Under Curve; Cross-Over Studies; Cyclin-Dependent Kinase 4; Fasting; Food-Drug Interactions; Healthy Volunteers; Humans; Internal Medicine; Medicine; Medicine & Public Health; Original; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Protein Kinase Inhibitors; Tablets; Therapeutic Equivalency
• ISSN: 1174-5886; 1179-6901
• DOI: 10.1007/s40268-022-00390-7

Background and Introduction SHR6390 is a new developed highly effective and selective small-molecule oral CDK4/6 inhibitor. We aimed to evaluate the effect of food on the pharmacokinetics of SHR6390 tablets. Methods In an open-label two-way crossover study, 24 healthy Chinese volunteers were randomly divided into Group A and Group B, and 12 volunteers in each group received a single oral dose of a SHR6390 150-mg tablet under fasting and high-fat conditions. Blood samples were collected and determined for pharmacokinetic analyses. A liquid chromatography-tandem mass spectrometry method was developed and validated for determining the SHR6390 concentration. Results The time to maximum plasma concentration was not significantly affected by a high-fat diet. Compared with the fasting group, maximum plasma concentration, i.e., the area under the concentration–time curve (AUC 0– t and AUC 0–∞ ) was altered significantly, as evidenced by an increase of 56.9%, 38.6%, and 37.5% respectively. We identified seven metabolites of SHR6390 from the plasma samples, and we found no sex differences in metabolic pathways. All treatment-emergent adverse events were Grade 1 or 2. Conclusions Food intake increased the maximum plasma concentration, AUC 0– t , and AUC 0–∞ significantly compared with the fasting condition. Meanwhile, single-dose SHR6390 for two treatment cycles is safe. SHR6390 was administered in a fasting status in the pivotal phase III study (NCT03927456) and chosen for the final drug label.