Ariel TOPLETZ-ERICKSON, Anthony LEE, JoAl Garrido MAYOR, Hsu-Tai LIU, Layth Imad ABDULRASOOL, Luke WALKER, Christopher James ENDRES
Tucatinib is a highly selective human epidermal growth factor receptor 2 (HER2) -directed tyrosine kinase inhibitor approved in multiple countries for metastatic HER2-positive breast cancer and in the US for metastatic HER2-postive metastatic colorectal cancer. This phase Ⅰ study (N＝36) compared the pharmacokinetic (PK) and safety profiles of tucatinib administered at 50-, 150-, and 300-mg doses taken twice daily orally in healthy Japanese (n＝18［n＝6 per tucatinib dose cohort］) and Caucasian volunteers (n＝18［n＝6 per tucatinib dose cohort］) to assess ethnicity effects on PK and dose proportionality of tucatinib. Ethnicity effects between both populations were evaluated using an analysis of covariance (ANCOVA) model and dose proportionality of tucatinib was assessed using a log-transformed linear regression model. Tucatinib steady-state exposure (AUCss) and maximum plasma concentration (Cmax) geometric mean values were similar between Japanese and Caucasian volunteers, with ANCOVA-adjusted geometric mean ratios (90％ confidence intervals) of 2.63 (1.04, 6.62), 1.11 (0.76, 1.62), and 1.33 (0.91, 1.95) for Cmax and 1.97 (0.85, 4.56), 1.05 (0.70, 1.58), and 1.04 (0.72, 1.49) for AUCss in the tucatinib 50-, 150-, and 300-mg cohorts, respectively. Thirty-three treatment-emergent adverse events (TEAEs) in 13 Caucasian volunteers and 2 TEAEs in 2 Japanese volunteers were reported. All TEAEs were grade 1, and the majority resolved by the end of study. At the approved therapeutic dose of 300 mg twice daily, tucatinib had a manageable safety profile and exposures were similar between Japanese and Caucasian volunteers. These findings indicate there is no need for dose alteration of tucatinib based on ethnicity.
{"title":"Pharmacokinetics and Safety of Tucatinib in Healthy Japanese and Caucasian Volunteers: Results From a Phase Ⅰ Study","authors":"Ariel TOPLETZ-ERICKSON, Anthony LEE, JoAl Garrido MAYOR, Hsu-Tai LIU, Layth Imad ABDULRASOOL, Luke WALKER, Christopher James ENDRES","doi":"10.3999/jscpt.54.5_187","DOIUrl":"https://doi.org/10.3999/jscpt.54.5_187","url":null,"abstract":"Tucatinib is a highly selective human epidermal growth factor receptor 2 (HER2) -directed tyrosine kinase inhibitor approved in multiple countries for metastatic HER2-positive breast cancer and in the US for metastatic HER2-postive metastatic colorectal cancer. This phase Ⅰ study (N＝36) compared the pharmacokinetic (PK) and safety profiles of tucatinib administered at 50-, 150-, and 300-mg doses taken twice daily orally in healthy Japanese (n＝18［n＝6 per tucatinib dose cohort］) and Caucasian volunteers (n＝18［n＝6 per tucatinib dose cohort］) to assess ethnicity effects on PK and dose proportionality of tucatinib. Ethnicity effects between both populations were evaluated using an analysis of covariance (ANCOVA) model and dose proportionality of tucatinib was assessed using a log-transformed linear regression model. Tucatinib steady-state exposure (AUCss) and maximum plasma concentration (Cmax) geometric mean values were similar between Japanese and Caucasian volunteers, with ANCOVA-adjusted geometric mean ratios (90％ confidence intervals) of 2.63 (1.04, 6.62), 1.11 (0.76, 1.62), and 1.33 (0.91, 1.95) for Cmax and 1.97 (0.85, 4.56), 1.05 (0.70, 1.58), and 1.04 (0.72, 1.49) for AUCss in the tucatinib 50-, 150-, and 300-mg cohorts, respectively. Thirty-three treatment-emergent adverse events (TEAEs) in 13 Caucasian volunteers and 2 TEAEs in 2 Japanese volunteers were reported. All TEAEs were grade 1, and the majority resolved by the end of study. At the approved therapeutic dose of 300 mg twice daily, tucatinib had a manageable safety profile and exposures were similar between Japanese and Caucasian volunteers. These findings indicate there is no need for dose alteration of tucatinib based on ethnicity.","PeriodicalId":14602,"journal":{"name":"JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135083147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yoichiro OGAMA, Hiroki SATO, Atsunori MIYATA, Koji KIJIMA, Yuji KUMAGAI
Objective: To assess the safety, tolerability, and pharmacokinetics of belumosudil, a selective Rho-associated coiled-coil-containing protein kinase 2 inhibitor, in healthy Japanese male adults, a phase Ⅰ, randomized, double-blind, placebo-controlled trial was conducted.
{"title":"Safety, Tolerability, and Pharmacokinetics of Belumosudil, a Selective Rho-associated Coiled-coil-containing Protein Kinase 2 Inhibitor, in Healthy Japanese Volunteers: A PhaseⅠ, Randomized, Controlled Trial","authors":"Yoichiro OGAMA, Hiroki SATO, Atsunori MIYATA, Koji KIJIMA, Yuji KUMAGAI","doi":"10.3999/jscpt.54.5_197","DOIUrl":"https://doi.org/10.3999/jscpt.54.5_197","url":null,"abstract":"Objective: To assess the safety, tolerability, and pharmacokinetics of belumosudil, a selective Rho-associated coiled-coil-containing protein kinase 2 inhibitor, in healthy Japanese male adults, a phase Ⅰ, randomized, double-blind, placebo-controlled trial was conducted.","PeriodicalId":14602,"journal":{"name":"JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135083334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Patient Training Initiatives on Drug Development and Future Challenges：Developing a Social Infrastructure for Patient Engagement in Drug Development","authors":"Yuta Kasai, Kenma Nozaki, Nobutaka Yagi, Shintaro Omuro, Keiko Omomo, Kotone Matsuyama","doi":"10.3999/jscpt.54.4_173","DOIUrl":"https://doi.org/10.3999/jscpt.54.4_173","url":null,"abstract":"","PeriodicalId":14602,"journal":{"name":"JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45121497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a Concept Sheet for Pediatric Clinical Trials","authors":"Kayoko Kikuchi, M. Sako, Hidefumi Nakamura","doi":"10.3999/jscpt.54.4_167","DOIUrl":"https://doi.org/10.3999/jscpt.54.4_167","url":null,"abstract":"","PeriodicalId":14602,"journal":{"name":"JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45163206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"2. Side Effects and Care of Molecular Targeted Drugs","authors":"Satomi YAMADA","doi":"10.3999/jscpt.54.3_123","DOIUrl":"https://doi.org/10.3999/jscpt.54.3_123","url":null,"abstract":"","PeriodicalId":14602,"journal":{"name":"JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135434235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：