Yan Li, Liangang Liu, Lian Huang, Xiaomin Wang, Matthew Hoffmann, Josephine Reyes, Maria Palmisano, Simon Zhou
{"title":"一项在健康受试者中进行的I期、开放标签、随机、交叉研究，以评估泊马度胺口服液悬浮液的生物利用度和食物效应。","authors":"Yan Li, Liangang Liu, Lian Huang, Xiaomin Wang, Matthew Hoffmann, Josephine Reyes, Maria Palmisano, Simon Zhou","doi":"10.2147/CPAA.S171735","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to evaluate the bioavailability of a pomalidomide oral liquid suspension relative to the commercial capsule formulation and to assess the food effect on the pomalidomide oral liquid suspension when administered as a single 4 mg dose.</p><p><strong>Methods: </strong>This was an open-label, randomized, three-period, two-sequence crossover study in healthy subjects consisting of a screening phase, a baseline assessment phase, a treatment phase with three periods, and a follow-up phone call phase. Blood samples for pharmacokinetics (PK) assessment were collected up to 48 h postdose during each treatment period. Safety was evaluated throughout the study.</p><p><strong>Results: </strong>Pomalidomide exposures were comparable in healthy subjects administered with a single oral 4 mg dose as the reference capsule or as the test liquid suspension formulations, demonstrated as the 90% confidence intervals of the geometric mean ratios for area under the plasma concentration-time curve calculated from time 0 to the last measurable concentration at time <i>t</i> (AUC<sub>0-t</sub>), area under the plasma concentration-time curve from time 0 to infinity (AUC<sub>0-∞</sub>), and peak (maximum) plasma drug concentration (<i>C</i><sub>max</sub>) were completely contained within the bioequivalence range of 80-125%. Administration of the pomalidomide liquid suspension with a high fat meal resulted in a 3.0 h delay in pomalidomide time to <i>C</i><sub>max</sub> (<i>t</i><sub>max</sub>) and an ~ 34.5% reduction in <i>C</i><sub>max</sub>. However, the AUCs were comparable after dose administration with and without food.</p><p><strong>Conclusion: </strong>A single oral dose of 4 mg of liquid suspension was bioequivalent to a single oral dose of 4 mg of capsule formulation. There was no clinically relevant impact of food on pomalidomide liquid suspension. Single oral doses of 4 mg pomalidomide were safe and well tolerated when administered as a liquid suspension under fed and fasted conditions or as a capsule under fasted conditions.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"89-99"},"PeriodicalIF":3.1000,"publicationDate":"2018-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S171735","citationCount":"3","resultStr":"{\"title\":\"A Phase I, open-label, randomized, crossover study in healthy subjects to evaluate the bioavailability of, and the food effect on, a pomalidomide oral liquid suspension.\",\"authors\":\"Yan Li, Liangang Liu, Lian Huang, Xiaomin Wang, Matthew Hoffmann, Josephine Reyes, Maria Palmisano, Simon Zhou\",\"doi\":\"10.2147/CPAA.S171735\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>The aim of this study was to evaluate the bioavailability of a pomalidomide oral liquid suspension relative to the commercial capsule formulation and to assess the food effect on the pomalidomide oral liquid suspension when administered as a single 4 mg dose.</p><p><strong>Methods: </strong>This was an open-label, randomized, three-period, two-sequence crossover study in healthy subjects consisting of a screening phase, a baseline assessment phase, a treatment phase with three periods, and a follow-up phone call phase. Blood samples for pharmacokinetics (PK) assessment were collected up to 48 h postdose during each treatment period. Safety was evaluated throughout the study.</p><p><strong>Results: </strong>Pomalidomide exposures were comparable in healthy subjects administered with a single oral 4 mg dose as the reference capsule or as the test liquid suspension formulations, demonstrated as the 90% confidence intervals of the geometric mean ratios for area under the plasma concentration-time curve calculated from time 0 to the last measurable concentration at time <i>t</i> (AUC<sub>0-t</sub>), area under the plasma concentration-time curve from time 0 to infinity (AUC<sub>0-∞</sub>), and peak (maximum) plasma drug concentration (<i>C</i><sub>max</sub>) were completely contained within the bioequivalence range of 80-125%. Administration of the pomalidomide liquid suspension with a high fat meal resulted in a 3.0 h delay in pomalidomide time to <i>C</i><sub>max</sub> (<i>t</i><sub>max</sub>) and an ~ 34.5% reduction in <i>C</i><sub>max</sub>. However, the AUCs were comparable after dose administration with and without food.</p><p><strong>Conclusion: </strong>A single oral dose of 4 mg of liquid suspension was bioequivalent to a single oral dose of 4 mg of capsule formulation. There was no clinically relevant impact of food on pomalidomide liquid suspension. Single oral doses of 4 mg pomalidomide were safe and well tolerated when administered as a liquid suspension under fed and fasted conditions or as a capsule under fasted conditions.</p>\",\"PeriodicalId\":10406,\"journal\":{\"name\":\"Clinical Pharmacology : Advances and Applications\",\"volume\":\"10 \",\"pages\":\"89-99\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2018-07-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.2147/CPAA.S171735\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Pharmacology : Advances and Applications\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/CPAA.S171735\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2018/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Pharmacology : Advances and Applications","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/CPAA.S171735","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
A Phase I, open-label, randomized, crossover study in healthy subjects to evaluate the bioavailability of, and the food effect on, a pomalidomide oral liquid suspension.
Objective: The aim of this study was to evaluate the bioavailability of a pomalidomide oral liquid suspension relative to the commercial capsule formulation and to assess the food effect on the pomalidomide oral liquid suspension when administered as a single 4 mg dose.
Methods: This was an open-label, randomized, three-period, two-sequence crossover study in healthy subjects consisting of a screening phase, a baseline assessment phase, a treatment phase with three periods, and a follow-up phone call phase. Blood samples for pharmacokinetics (PK) assessment were collected up to 48 h postdose during each treatment period. Safety was evaluated throughout the study.
Results: Pomalidomide exposures were comparable in healthy subjects administered with a single oral 4 mg dose as the reference capsule or as the test liquid suspension formulations, demonstrated as the 90% confidence intervals of the geometric mean ratios for area under the plasma concentration-time curve calculated from time 0 to the last measurable concentration at time t (AUC0-t), area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞), and peak (maximum) plasma drug concentration (Cmax) were completely contained within the bioequivalence range of 80-125%. Administration of the pomalidomide liquid suspension with a high fat meal resulted in a 3.0 h delay in pomalidomide time to Cmax (tmax) and an ~ 34.5% reduction in Cmax. However, the AUCs were comparable after dose administration with and without food.
Conclusion: A single oral dose of 4 mg of liquid suspension was bioequivalent to a single oral dose of 4 mg of capsule formulation. There was no clinically relevant impact of food on pomalidomide liquid suspension. Single oral doses of 4 mg pomalidomide were safe and well tolerated when administered as a liquid suspension under fed and fasted conditions or as a capsule under fasted conditions.
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