Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults
Abstract Background and Objectives This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. Methods This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years)...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Adis, Springer Healthcare
2023-11-01
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| Series: | Drugs in R&D |
| Online Access: | https://doi.org/10.1007/s40268-023-00446-2 |
| _version_ | 1797412312458461184 |
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| author | Huiling Qin Yan Tan Lei Diao Ai-Min Hui Zhuli Wu Yongchun Zhou Juan Sun Xiao Xiang Jingjun Qiu Wei Hu |
| author_facet | Huiling Qin Yan Tan Lei Diao Ai-Min Hui Zhuli Wu Yongchun Zhou Juan Sun Xiao Xiang Jingjun Qiu Wei Hu |
| author_sort | Huiling Qin |
| collection | DOAJ |
| description | Abstract Background and Objectives This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. Methods This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80–1.25. Results In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (C max; GMR: 109.1% [90% CI 103.1–115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration–time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3–110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6–110.6]). In both groups, the median time to maximum plasma concentration (t max) was around 6 h and mean plasma half-life (t ½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. Conclusions A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs. |
| first_indexed | 2024-03-09T05:00:20Z |
| format | Article |
| id | doaj.art-a513998392c64eec8b24dd33ea1d2764 |
| institution | Directory Open Access Journal |
| issn | 1174-5886 1179-6901 |
| language | English |
| last_indexed | 2024-03-09T05:00:20Z |
| publishDate | 2023-11-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Drugs in R&D |
| spelling | doaj.art-a513998392c64eec8b24dd33ea1d27642023-12-03T13:00:49ZengAdis, Springer HealthcareDrugs in R&D1174-58861179-69012023-11-0123446547310.1007/s40268-023-00446-2Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese AdultsHuiling Qin0Yan Tan1Lei Diao2Ai-Min Hui3Zhuli Wu4Yongchun Zhou5Juan Sun6Xiao Xiang7Jingjun Qiu8Wei Hu9Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical UniversityShanghai Fosun Pharmaceutical Development Co., Ltd.Shanghai Fosun Pharmaceutical Development Co., Ltd.EnCureGen PharmaShanghai Fosun Pharmaceutical Development Co., Ltd.Wanbang BiopharmaceuticalsShanghai Fosun Pharmaceutical Development Co., Ltd.Shanghai Fosun Pharmaceutical Development Co., Ltd.Shanghai Fosun Pharmaceutical Development Co., Ltd.Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical UniversityAbstract Background and Objectives This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. Methods This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80–1.25. Results In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (C max; GMR: 109.1% [90% CI 103.1–115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration–time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3–110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6–110.6]). In both groups, the median time to maximum plasma concentration (t max) was around 6 h and mean plasma half-life (t ½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. Conclusions A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.https://doi.org/10.1007/s40268-023-00446-2 |
| spellingShingle | Huiling Qin Yan Tan Lei Diao Ai-Min Hui Zhuli Wu Yongchun Zhou Juan Sun Xiao Xiang Jingjun Qiu Wei Hu Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults Drugs in R&D |
| title | Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults |
| title_full | Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults |
| title_fullStr | Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults |
| title_full_unstemmed | Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults |
| title_short | Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults |
| title_sort | effect of high fat food on the pharmacokinetic profile and safety of saf 189s an alk ros1 inhibitor in healthy chinese adults |
| url | https://doi.org/10.1007/s40268-023-00446-2 |
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