Ashit Trivedi, Y-H Kiang, Robert E Saw, Guilong Charles Cheng, Omar Mather, Silvia Vega, Jennifer Hellawell, Edward Lee
{"title":"AMG 986片剂和胶囊制剂在健康成年受试者中的药代动力学和安全性评估：一项I期开放标签随机研究","authors":"Ashit Trivedi, Y-H Kiang, Robert E Saw, Guilong Charles Cheng, Omar Mather, Silvia Vega, Jennifer Hellawell, Edward Lee","doi":"10.1007/s40268-022-00388-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>AMG 986 is a first-in-class, novel apelin receptor small molecule agonist initially developed for the treatment of heart failure. The current phase I study was conducted to evaluate the pharmacokinetics and safety of a single-dose 200-mg capsule formulation of AMG 986 relative to the tablet formulation in 12 healthy subjects.</p><p><strong>Methods: </strong>In a two-period, two-way crossover design, eligible subjects were randomized 1:1 to tablet/capsule or capsule/tablet treatment sequences; each treatment sequence lasted for approximately 6 days and comprised six subjects.</p><p><strong>Results: </strong>Following a single oral dose of AMG 986, the geometric mean maximum observed concentration (C<sub>max</sub>) values were 9670 ng/mL and 6920 ng/mL and the geometric mean area under the curve from time zero to 120 h (AUC<sub>0-120h</sub>) values were 68,000 ng*h/mL and 59,900 ng*h/mL for the tablet and capsule, respectively. The geometric least squares means (90% confidence interval [90% CI]) for the ratios of capsule/tablet were 0.88 (90% CI 0.81-0.96) and 0.72 (90% CI 0.57-0.91) for AUC<sub>0-120h</sub> and C<sub>max</sub>, respectively. AMG 986 had an acceptable safety profile; all adverse events were grade 1 or 2 in severity.</p><p><strong>Conclusion: </strong>There was a modest 12% decrease in AUC<sub>0-120h</sub> and a 28% decrease in C<sub>max</sub> with the AMG 986 capsule versus the tablet. These differences are not considered to be clinically relevant, suggesting the capsule formulation can be used in subsequent clinical studies of AMG 986.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"22 1","pages":"147-154"},"PeriodicalIF":2.2000,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167409/pdf/","citationCount":"2","resultStr":"{\"title\":\"Evaluation of the Pharmacokinetics and Safety of AMG 986 Tablet and Capsule Formulations in Healthy Adult Subjects: A Phase I, Open-Label, Randomized Study.\",\"authors\":\"Ashit Trivedi, Y-H Kiang, Robert E Saw, Guilong Charles Cheng, Omar Mather, Silvia Vega, Jennifer Hellawell, Edward Lee\",\"doi\":\"10.1007/s40268-022-00388-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>AMG 986 is a first-in-class, novel apelin receptor small molecule agonist initially developed for the treatment of heart failure. The current phase I study was conducted to evaluate the pharmacokinetics and safety of a single-dose 200-mg capsule formulation of AMG 986 relative to the tablet formulation in 12 healthy subjects.</p><p><strong>Methods: </strong>In a two-period, two-way crossover design, eligible subjects were randomized 1:1 to tablet/capsule or capsule/tablet treatment sequences; each treatment sequence lasted for approximately 6 days and comprised six subjects.</p><p><strong>Results: </strong>Following a single oral dose of AMG 986, the geometric mean maximum observed concentration (C<sub>max</sub>) values were 9670 ng/mL and 6920 ng/mL and the geometric mean area under the curve from time zero to 120 h (AUC<sub>0-120h</sub>) values were 68,000 ng*h/mL and 59,900 ng*h/mL for the tablet and capsule, respectively. The geometric least squares means (90% confidence interval [90% CI]) for the ratios of capsule/tablet were 0.88 (90% CI 0.81-0.96) and 0.72 (90% CI 0.57-0.91) for AUC<sub>0-120h</sub> and C<sub>max</sub>, respectively. AMG 986 had an acceptable safety profile; all adverse events were grade 1 or 2 in severity.</p><p><strong>Conclusion: </strong>There was a modest 12% decrease in AUC<sub>0-120h</sub> and a 28% decrease in C<sub>max</sub> with the AMG 986 capsule versus the tablet. These differences are not considered to be clinically relevant, suggesting the capsule formulation can be used in subsequent clinical studies of AMG 986.</p>\",\"PeriodicalId\":49258,\"journal\":{\"name\":\"Drugs in Research & Development\",\"volume\":\"22 1\",\"pages\":\"147-154\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2022-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167409/pdf/\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drugs in Research & Development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40268-022-00388-1\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/4/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drugs in Research & Development","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40268-022-00388-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/4/12 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Evaluation of the Pharmacokinetics and Safety of AMG 986 Tablet and Capsule Formulations in Healthy Adult Subjects: A Phase I, Open-Label, Randomized Study.
Background and objective: AMG 986 is a first-in-class, novel apelin receptor small molecule agonist initially developed for the treatment of heart failure. The current phase I study was conducted to evaluate the pharmacokinetics and safety of a single-dose 200-mg capsule formulation of AMG 986 relative to the tablet formulation in 12 healthy subjects.
Methods: In a two-period, two-way crossover design, eligible subjects were randomized 1:1 to tablet/capsule or capsule/tablet treatment sequences; each treatment sequence lasted for approximately 6 days and comprised six subjects.
Results: Following a single oral dose of AMG 986, the geometric mean maximum observed concentration (Cmax) values were 9670 ng/mL and 6920 ng/mL and the geometric mean area under the curve from time zero to 120 h (AUC0-120h) values were 68,000 ng*h/mL and 59,900 ng*h/mL for the tablet and capsule, respectively. The geometric least squares means (90% confidence interval [90% CI]) for the ratios of capsule/tablet were 0.88 (90% CI 0.81-0.96) and 0.72 (90% CI 0.57-0.91) for AUC0-120h and Cmax, respectively. AMG 986 had an acceptable safety profile; all adverse events were grade 1 or 2 in severity.
Conclusion: There was a modest 12% decrease in AUC0-120h and a 28% decrease in Cmax with the AMG 986 capsule versus the tablet. These differences are not considered to be clinically relevant, suggesting the capsule formulation can be used in subsequent clinical studies of AMG 986.
期刊介绍：
Drugs in R&D is an international, peer reviewed, open access, online only journal, and provides timely information from all phases of drug research and development that will inform clinical practice. Healthcare decision makers are thus provided with knowledge about the developing place of a drug in therapy.
The Journal includes:
Clinical research on new and established drugs;
Preclinical research of direct relevance to clinical drug development;
Short communications and case study reports that meet the above criteria will also be considered;
Reviews may also be considered.
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