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Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects
BACKGROUND AND OBJECTIVES: Data on the effect of food on the pharmacokinetics of senaparib (previously IMP4297), an oral poly (adenosine diphosphate-ribose) polymerase inhibitor, are limited. This study was conducted to evaluate the effect of food on the pharmacokinetics of senaparib in healthy Chin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9617823/ https://www.ncbi.nlm.nih.gov/pubmed/36239914 http://dx.doi.org/10.1007/s40261-022-01198-8 |
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author | Meng, Xianmin Lin, Xiaoyan Jiang, Rongrong Lu, Yan Zeng, Liyan Cao, Ming Zhang, Jianliang |
author_facet | Meng, Xianmin Lin, Xiaoyan Jiang, Rongrong Lu, Yan Zeng, Liyan Cao, Ming Zhang, Jianliang |
author_sort | Meng, Xianmin |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Data on the effect of food on the pharmacokinetics of senaparib (previously IMP4297), an oral poly (adenosine diphosphate-ribose) polymerase inhibitor, are limited. This study was conducted to evaluate the effect of food on the pharmacokinetics of senaparib in healthy Chinese subjects. METHODS: This is a phase I, open-label, randomized, single-dose, two-way crossover study. Healthy Chinese male subjects were randomized 1:1 to receive a single dose of senaparib 100 mg in two prandial states: fasted or after a high-fat meal; subjects were given a second dose after switching prandial states and a washout period of at least 7 days. Pharmacokinetics were assessed at pre-dose and up to 72 h post-dose. Safety was assessed throughout the study. RESULTS: Sixteen subjects were randomized and included in the pharmacokinetic analysis; 15 completed the study. The presence of food slowed the rate of senaparib absorption (time to maximum concentration) by ~ 3 h and reduced the maximum concentration of senaparib by ~ 24%. Total exposure to senaparib was higher in the fed than fasted state; senaparib area under the plasma concentration–time curve from time zero to the last measurable concentration and area under the plasma concentration–time curve from time zero to infinity were increased by ~ 24 and ~28%, respectively. Safety profiles were similar in both prandial states. All treatment-emergent adverse events were grade 1 in severity; no serious adverse events or deaths were reported. CONCLUSIONS: Food slightly decreased the rate and increased the extent of senaparib absorption following oral administration. However, the effect of food on various exposure parameters was not considered clinically meaningful. Safety data were consistent with the known profile of senaparib and senaparib was well tolerated in the fed and fasted states in healthy subjects. These results indicated that senaparib could be administered orally with or without food. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04057729. |
format | Online Article Text |
id | pubmed-9617823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-96178232022-10-31 Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects Meng, Xianmin Lin, Xiaoyan Jiang, Rongrong Lu, Yan Zeng, Liyan Cao, Ming Zhang, Jianliang Clin Drug Investig Original Research Article BACKGROUND AND OBJECTIVES: Data on the effect of food on the pharmacokinetics of senaparib (previously IMP4297), an oral poly (adenosine diphosphate-ribose) polymerase inhibitor, are limited. This study was conducted to evaluate the effect of food on the pharmacokinetics of senaparib in healthy Chinese subjects. METHODS: This is a phase I, open-label, randomized, single-dose, two-way crossover study. Healthy Chinese male subjects were randomized 1:1 to receive a single dose of senaparib 100 mg in two prandial states: fasted or after a high-fat meal; subjects were given a second dose after switching prandial states and a washout period of at least 7 days. Pharmacokinetics were assessed at pre-dose and up to 72 h post-dose. Safety was assessed throughout the study. RESULTS: Sixteen subjects were randomized and included in the pharmacokinetic analysis; 15 completed the study. The presence of food slowed the rate of senaparib absorption (time to maximum concentration) by ~ 3 h and reduced the maximum concentration of senaparib by ~ 24%. Total exposure to senaparib was higher in the fed than fasted state; senaparib area under the plasma concentration–time curve from time zero to the last measurable concentration and area under the plasma concentration–time curve from time zero to infinity were increased by ~ 24 and ~28%, respectively. Safety profiles were similar in both prandial states. All treatment-emergent adverse events were grade 1 in severity; no serious adverse events or deaths were reported. CONCLUSIONS: Food slightly decreased the rate and increased the extent of senaparib absorption following oral administration. However, the effect of food on various exposure parameters was not considered clinically meaningful. Safety data were consistent with the known profile of senaparib and senaparib was well tolerated in the fed and fasted states in healthy subjects. These results indicated that senaparib could be administered orally with or without food. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04057729. Springer International Publishing 2022-10-14 2022 /pmc/articles/PMC9617823/ /pubmed/36239914 http://dx.doi.org/10.1007/s40261-022-01198-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Article Meng, Xianmin Lin, Xiaoyan Jiang, Rongrong Lu, Yan Zeng, Liyan Cao, Ming Zhang, Jianliang Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects |
title | Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects |
title_full | Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects |
title_fullStr | Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects |
title_full_unstemmed | Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects |
title_short | Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects |
title_sort | effect of food on the pharmacokinetics of senaparib (imp4297) in healthy chinese subjects |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9617823/ https://www.ncbi.nlm.nih.gov/pubmed/36239914 http://dx.doi.org/10.1007/s40261-022-01198-8 |
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