Clinical Pharmacology in Drug Development最新文献_第8页

Bioequivalence and Tolerability of 2 Lurasidone Formulations: A Randomized, Single-Dose, 2-Period, Crossover Study in Healthy Chinese Subjects Under Fasting and Fed Conditions 两种鲁拉西酮制剂的生物等效性和耐受性：一项随机、单剂量、2期、交叉研究，在空腹和进食条件下进行。

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-28 DOI: 10.1002/cpdd.1529

Hengyi Yu, Yinian Fang, Xingxing Qi, Pan Luo, Zheng He, Kaifu Wang, Yongfang Lei, Donglin Zhang, Qin Zuo, Chang Liu, Qian Chen, Dong Liu, Xiuhua Ren

{"title":"Bioequivalence and Tolerability of 2 Lurasidone Formulations: A Randomized, Single-Dose, 2-Period, Crossover Study in Healthy Chinese Subjects Under Fasting and Fed Conditions","authors":"Hengyi Yu, Yinian Fang, Xingxing Qi, Pan Luo, Zheng He, Kaifu Wang, Yongfang Lei, Donglin Zhang, Qin Zuo, Chang Liu, Qian Chen, Dong Liu, Xiuhua Ren","doi":"10.1002/cpdd.1529","DOIUrl":"10.1002/cpdd.1529","url":null,"abstract":"Lurasidone is utilized in the treatment of schizophrenia and bipolar depression in adults and adolescents. In this work, a randomized, single-dose, 2-period crossover study was designed and conducted to evaluate the bioequivalence and safety of 2 lurasidone tablets. A total of 111 healthy Chinese subjects received a single dose of 40 mg lurasidone test (T) or reference (R) tablets under fasting or fed conditions, with a 7-day washout period. Blood samples were collected and lurasidone plasma concentration was quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic properties were determined by a non-compartmental analysis, and Cmax, AUC0-t, and AUC0-inf were used for bioequivalence evaluation. As a result, the 90% confidence intervals of the geometric mean ratios between T and R fell within 80%-125% whether under fasting or fed conditions, indicating that the 2 lurasidone formulations were bioequivalent. Meanwhile, the Cmax and AUC of both T and R were approximately 2-3 times higher in the fed state compared to the fasting state. In addition, all adverse events (AEs) were classified into grade 1, and no serious or new AEs were reported. Additionally, a shorter t1/2 of the reference tablet was observed in this study compared to that of the other bioequivalence study conducted in older healthy Chinese subjects, which should be verified in the future.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 6","pages":"436-442"},"PeriodicalIF":1.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Patients With Mild or Moderate Hepatic Impairment Versus Participants With Normal Hepatic Function: A Phase 1 Study TPN171 （PDE5抑制剂）在轻度或中度肝功能损害患者与正常肝功能患者中的药代动力学和安全性：一项I期研究

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-25 DOI: 10.1002/cpdd.1535

Jing Zhou, Hong Zhang, Yanhua Ding, Zhen Wang, Yu Wang, Jiaxiang Juan, Zhicheng Jiang, Hong Chen

{"title":"Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Patients With Mild or Moderate Hepatic Impairment Versus Participants With Normal Hepatic Function: A Phase 1 Study","authors":"Jing Zhou, Hong Zhang, Yanhua Ding, Zhen Wang, Yu Wang, Jiaxiang Juan, Zhicheng Jiang, Hong Chen","doi":"10.1002/cpdd.1535","DOIUrl":"10.1002/cpdd.1535","url":null,"abstract":"TPN171 is a phosphodiesterase-5 inhibitor. It is currently being developed in China to treat pulmonary arterial hypertension and erectile dysfunction (ED). This study aimed to compare the pharmacokinetics and safety of TPN171 across participants with normal hepatic function and hepatic impairment (HI). An open-label, single-dose, parallel-group study enrolled participants with normal hepatic function (group C) and mild-to-moderate HI (groups A and B). In each cohort, 8 participants completed the study. Blood samples were collected up to 72 hours after 10 mg oral TPN171 administration. The maximum plasma concentration (Cmax), area under the plasma concentration–time curve from time zero to the last quantifiable concentration (AUC0-t), and AUC extrapolated to infinite time (AUC0-∞) were compared between the groups. Cmax, AUC0-t, and AUC0-∞ were higher in groups A and B than in group C (geometric mean ratios 1.17-1.20, 1.46-1.53, and 1.45-1.54, respectively), while the elimination half-time was prolonged and clearance was reduced in the HI groups. All adverse events were not serious and no participant withdrew from this study. Considering the increase in TPN171 plasma exposure, the highest dose of 5 mg TPN171 is recommended in patients with ED having mild-to-moderate HI.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 6","pages":"472-478"},"PeriodicalIF":1.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioequivalence Study of Two Empagliflozin Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions 两种恩格列净片在空腹和空腹条件下的生物等效性研究。

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-25 DOI: 10.1002/cpdd.1530

Yuyan Lei, Yuan Liu, Lichen Gao, Xueqiong Peng, Lulu Chen, Chao Li, Weiming Chen, Junmei Xu, Dongsheng Ouyang, Xiaohui Li

{"title":"Bioequivalence Study of Two Empagliflozin Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions","authors":"Yuyan Lei, Yuan Liu, Lichen Gao, Xueqiong Peng, Lulu Chen, Chao Li, Weiming Chen, Junmei Xu, Dongsheng Ouyang, Xiaohui Li","doi":"10.1002/cpdd.1530","DOIUrl":"10.1002/cpdd.1530","url":null,"abstract":"Empagliflozin is a highly selective sodium-glucose cotransporter 2 inhibitor and an effective medication for treating diabetes. This study aimed to assess the pharmacokinetics and bioequivalence of two 10-mg empagliflozin tablets in healthy Chinese subjects and examine food's effect on absorption. The research was conducted as a single-center, randomized, open-label, single-dose, 2-way crossover study involving 47 subjects (fasting: n = 23, fed: n = 24). Subjects received either the test or reference drug and switched to the alternative after a 7-day washout period. Blood samples were collected before administration and up to 48 hours after dosing, analyzed using validated liquid chromatography-tandem mass spectrometry techniques to determine empagliflozin levels. In both studies, all 23 subjects completed the study phases under fasting and fed conditions. In both scenarios, when comparing the test and reference formulations, the 90% confidence intervals for the geometric mean ratios of maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable concentration, and area under the concentration-time curve from time 0 to infinity fell within the bioequivalence threshold of 80%-125%, confirming their acceptability. The study found that a high-fat meal slightly reduced drug exposure and slightly accelerated absorption. No serious adverse events were observed. This research confirmed the pharmacokinetic similarity of the 2 empagliflozin formulations and demonstrated their good tolerance under fasting and fed conditions.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 7","pages":"542-548"},"PeriodicalIF":1.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Evaluation of Potential Interaction Between Bemnifosbuvir and Ruzasvir With an Assessment of Food Effect: Results of a Phase 1 Study in Healthy Participants 贝尼非布韦和鲁扎韦潜在相互作用与食物效应评估的临床评价：健康参与者的1期研究结果

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-24 DOI: 10.1002/cpdd.1540

Xiao-Jian Zhou, Gaetano Morelli, Maureen Montrond, Shannan Lynch, Keith Pietropaolo, Bruce Belanger, Arantxa Horga, Janet Hammond

{"title":"Clinical Evaluation of Potential Interaction Between Bemnifosbuvir and Ruzasvir With an Assessment of Food Effect: Results of a Phase 1 Study in Healthy Participants","authors":"Xiao-Jian Zhou, Gaetano Morelli, Maureen Montrond, Shannan Lynch, Keith Pietropaolo, Bruce Belanger, Arantxa Horga, Janet Hammond","doi":"10.1002/cpdd.1540","DOIUrl":"10.1002/cpdd.1540","url":null,"abstract":"A combination of nucleotide hepatitis C virus (HCV) nonstructural protein (NS) 5B and 5A inhibitors is a preferred standard of care for treating chronic HCV. Bemnifosbuvir is a novel oral guanosine nucleotide prodrug with potent pan-genotypic inhibitory activity against HCV NS5B. Ruzasvir, a small-molecule NS5A inhibitor, has demonstrated improved anti-HCV activity compared with first-generation NS5A inhibitors. Clinical studies have demonstrated favorable efficacy and safety of bemnifosbuvir and ruzasvir in combination with other NS5A and NS5B inhibitors, respectively. A Phase 1 study in healthy participants was conducted to assess the drug-drug interaction potential between bemnifosbuvir and ruzasvir, as well as food effects following coadministration of both compounds. Under fasted conditions, the peak, trough, and total exposure to bemnifosbuvir and its metabolites were increased upon coadministration with ruzasvir (by a maximum of 33% vs bemnifosbuvir alone), whereas the corresponding values for ruzasvir were decreased upon coadministration with bemnifosbuvir (by a maximum of 26% vs ruzasvir alone). Food delayed peak exposure to both drugs (by up to 2 hours) while increasing their peak and total exposure by up to 63%. No serious adverse events or premature drug discontinuations were reported. Overall, the study results support further evaluation of bemnifosbuvir and ruzasvir combination therapy for treating chronic HCV.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 6","pages":"461-471"},"PeriodicalIF":1.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extrapolation of Midazolam Disposition in Neonates Using Physiological-Based Pharmacokinetic/Pharmacodynamic Modeling 使用基于生理的药代动力学/药效学模型推断咪达唑仑在新生儿中的处置。

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-24 DOI: 10.1002/cpdd.1531

Tangping Zhao, Zhanhui Lv, Sufeng Zhou, Lu Wang, Tongtong Li, Jinying Zhu, Feng Shao

{"title":"Extrapolation of Midazolam Disposition in Neonates Using Physiological-Based Pharmacokinetic/Pharmacodynamic Modeling","authors":"Tangping Zhao, Zhanhui Lv, Sufeng Zhou, Lu Wang, Tongtong Li, Jinying Zhu, Feng Shao","doi":"10.1002/cpdd.1531","DOIUrl":"10.1002/cpdd.1531","url":null,"abstract":"There is a shortage of data in clinical studies of neonatal populations, which often utilize extrapolation strategies and model simulation techniques to support drug development and clinical applications. This study established an adult physiological-based pharmacokinetic/pharmacodynamic (PBPK/PD) model in the modeling software and extended it to neonates using pediatric extrapolation strategies based on maturation formulas for plasma albumin and CYP3A4/5. The neonatal model was then utilized to simulate midazolam dosage regimens for sedation in newborns. Individualized validation for adults indicated that 95.1% of predicted concentration values and all area under curve (AUC) values fell within a 2-fold range. The extrapolated neonatal model showed 84.4% of predicted concentrations within 2-fold, an absolute average fold error (AAFE) valuen <2, and an average fold error (AFE) value between 0.5 and 1.5, confirming the model's adequacy. The validated neonatal PBPK/PD model indicated that virtual term neonates maintained the target plasma concentration for 25 hours with the recommended dosage (0.06 mg/kg/h, intravenous infusion 12 hours). Premature infants may require a slightly higher dose than the label's recommendation (0.03 mg/kg/h, intravenous infusion 12 hours). Our findings recommend this research strategy based on extrapolation and model simulation for drug dose prediction and optimization in the neonatal population.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 6","pages":"415-427"},"PeriodicalIF":1.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Adults with Renal Impairment 一项评估成人肾脏损害患者PDE5抑制剂TPN171的药代动力学和安全性的I期研究

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-21 DOI: 10.1002/cpdd.1536

Ping Fu, Yi Song, Chao Hu, Xiaolan Yong, Yang Yu, Yi Chen, Ying Wang, Xiaohong Zhu, Zhen Wang, Yu Wang, Jiaxiang Juan, Yuan Chen, Jia Miao

{"title":"A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Adults with Renal Impairment","authors":"Ping Fu, Yi Song, Chao Hu, Xiaolan Yong, Yang Yu, Yi Chen, Ying Wang, Xiaohong Zhu, Zhen Wang, Yu Wang, Jiaxiang Juan, Yuan Chen, Jia Miao","doi":"10.1002/cpdd.1536","DOIUrl":"10.1002/cpdd.1536","url":null,"abstract":"TPN171, a phosphodiesterase 5 inhibitor, is under development for the treatment of male erectile dysfunction and pulmonary arterial hypertension in China. To investigate the pharmacokinetic properties and safety of TPN171 in individuals with severe renal impairment and normal renal function, an open-label, single-dose, parallel-group phase 1 study was conducted in 8 participants with severe renal impairment (glomerular filtration rate within 15-29 mL/min) and 8 participants having normal renal function, who received TNP171 tablets (10 mg) in the fasting state. As compared with those with normal renal function, the geometric mean ratios for maximum plasma concentration (Cmax), the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t), and AUC extrapolated to infinite time (AUC0-∞) were 74.3%, 138%, and 137%, respectively. Elimination half-life was prolonged and clearance was decreased in severe renal impairment group. The adverse reaction rate showed no significant difference. All adverse events were mild intensity, and no participant was discontinued in this study. In conclusion, TPN171 can be cautiously used in patients with mild to severe renal impairment.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 6","pages":"479-486"},"PeriodicalIF":1.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative Bioequivalence Study of 2 Fixed-Dose Combinations of Vildagliptin and Metformin at a Tablet Strength of 50/1000 mg in Moroccan Volunteers 维格列汀和二甲双胍两种固定剂量组合片剂强度为50/ 1000mg在摩洛哥志愿者中的生物等效性比较研究。

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-21 DOI: 10.1002/cpdd.1528

Salma Lazrak, Oumaima Ouaouda, Jalal Bektachi, Mohamed Ali Iraqi, Choukri El Khabbaz, Yahya Cherrah

{"title":"Comparative Bioequivalence Study of 2 Fixed-Dose Combinations of Vildagliptin and Metformin at a Tablet Strength of 50/1000 mg in Moroccan Volunteers","authors":"Salma Lazrak, Oumaima Ouaouda, Jalal Bektachi, Mohamed Ali Iraqi, Choukri El Khabbaz, Yahya Cherrah","doi":"10.1002/cpdd.1528","DOIUrl":"10.1002/cpdd.1528","url":null,"abstract":"This study evaluates the bioequivalence of 2 fixed-dose combinations of vildagliptin (50 mg) and metformin (1000 mg) in healthy Moroccan volunteers. A single-dose, randomized, simple-blind, 2-sequence, 2-period crossover design was conducted with 30 participants, 28 of whom completed the study. The test product was compared to the reference product (by measuring pharmacokinetic parameters, including maximum plasma concentration, area under the concentration–time curve (AUC) from time zero to the last measurable time point, AUC from time zero extrapolated to infinity, and time to maximum concentration. Blood samples were collected at predefined intervals after dosing, and plasma concentrations of vildagliptin and metformin were determined using a validated liquid chromatography–tandem mass spectrometry method. Pharmacokinetic analysis showed comparable results between the 2 formulations. Both products met the bioequivalence criteria of 80%-125% for maximum plasma concentration and AUC. Safety assessments revealed no serious adverse events, and both products were well tolerated. The study concluded that the test product is bioequivalent to the reference, supporting its therapeutic interchangeability in managing type 2 diabetes mellitus.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 6","pages":"428-435"},"PeriodicalIF":1.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Phase 1 Study to Evaluate the Absorption, Metabolism, and Disposition of Dordaviprone in Healthy Adult Participants 一项评估健康成年参与者中Dordaviprone的吸收、代谢和处置的一期研究。

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-17 DOI: 10.1002/cpdd.1541

Yohannes Teffera, Tim Tippin, Angela Bartkus, Francine A. de Castro, Shamia L. Faison, Marion Morrison, Mark J. Mullin, Odin Naderer

{"title":"A Phase 1 Study to Evaluate the Absorption, Metabolism, and Disposition of Dordaviprone in Healthy Adult Participants","authors":"Yohannes Teffera, Tim Tippin, Angela Bartkus, Francine A. de Castro, Shamia L. Faison, Marion Morrison, Mark J. Mullin, Odin Naderer","doi":"10.1002/cpdd.1541","DOIUrl":"10.1002/cpdd.1541","url":null,"abstract":"Dordaviprone (ONC201) is a novel, small-molecule imipridone with antitumor activity in patients with a glioma. Six healthy male participants received a single 625-mg (100-µCi) oral dose of [14C]-dordaviprone. Blood, plasma, urine, and feces were collected up to 288 hours after dosing and analyzed by liquid scintillation counting. Metabolite profiles were evaluated using liquid chromatography-radiometric detection, and metabolite identification was accomplished by liquid chromatography with tandem mass spectrometry. Concentrations of drug-derived radioactivity in blood and plasma peaked at 1 hour after dosing and were below the limit of quantitation by 72 hours (whole blood) to 96 hours (plasma) after dosing. Seventy-one percent of the administered radioactivity was recovered in urine and 20% in feces. In plasma, the major circulating compounds were dordaviprone and the inactive metabolite ONC207, each contributing approximately one third of the total radioactivity area under the curve. Of the 19 metabolites identified in plasma, no other single metabolite contributed more than 10% to the total radioactivity area under the curve. Unchanged dordaviprone was a minor component in excreta (less than 0.3%), with multiple metabolites identified in urine and feces. Given the lack of dordaviprone in excreta and the metabolites formed, the primary route for dordaviprone elimination was through urinary excretion of oxidative metabolites.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 7","pages":"549-556"},"PeriodicalIF":1.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Phase 1C, Open Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of DM199 Administered Intravenously with a Polyvinyl Chloride Bag in Adult Healthy Subjects and Adults Recently Taking Angiotensin-Converting Enzyme Inhibitors 一项1C期、开放标签、单次递增剂量研究，评估成年健康受试者和近期服用血管紧张素转换酶抑制剂的成年人用聚乙烯袋静脉注射DM199的安全性、耐受性和药代动力学。

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-16 DOI: 10.1002/cpdd.1534

Michael Giuffre, Annette D. Lista, Nick Paulson, Lorianne Masuoka

{"title":"A Phase 1C, Open Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of DM199 Administered Intravenously with a Polyvinyl Chloride Bag in Adult Healthy Subjects and Adults Recently Taking Angiotensin-Converting Enzyme Inhibitors","authors":"Michael Giuffre, Annette D. Lista, Nick Paulson, Lorianne Masuoka","doi":"10.1002/cpdd.1534","DOIUrl":"10.1002/cpdd.1534","url":null,"abstract":"This small phase 1C, open-label, single ascending dose study evaluated the safety, tolerability, and pharmacokinetics (PKs) of DM199, a recombinant form of human tissue kallikrein-1 (KLK1). A small sample size of both healthy subjects and hypertensive adults recently taking angiotensin-converting enzyme inhibitors was studied. KLK1 has a known role in vasodilation and blood flow regulation, with potential implications for treatment of acute ischemic stroke (AIS) by focally enhancing cerebral perfusion. A total of 12 subjects were enrolled; 9 healthy subjects received escalating doses of DM199 (0.1-0.5 µg/kg), while 3 hypertensive subjects received the maximum tolerated dose of 0.5 µg/kg. Safety assessments indicated that DM199 was well tolerated, with mild adverse events reported, such as headache and flushing. No infusion-related hypotensive events occurred, and all subjects completed the study without significant clinical issues. The study was performed following prior PK analyses revealing that DM199 exposure was greater when administered with polyvinyl chloride infusion materials compared with polyolefin infusion materials. This study supports a revised dosing strategy for DM199 in the ongoing ReMEDy2 trial for AIS and highlights the need for careful consideration of the risk-benefit profile in the clinical context of AIS treatment.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 6","pages":"452-460"},"PeriodicalIF":1.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics and Safety of a Fixed-Dose Combination of Alogliptin and Extended-Release Metformin Under Fasting and/or Fed Conditions in Healthy Adults 健康成人空腹和/或非空腹进食条件下阿格列汀和缓释二甲双胍固定剂量联合用药的药代动力学和安全性

IF 1.8 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-16 DOI: 10.1002/cpdd.1532

Ji Hye Song, Jae Hoon Kim, Jang Hee Hong, Jin-Gyu Jung, Sun Young Park, Jung Sunwoo

{"title":"Pharmacokinetics and Safety of a Fixed-Dose Combination of Alogliptin and Extended-Release Metformin Under Fasting and/or Fed Conditions in Healthy Adults","authors":"Ji Hye Song, Jae Hoon Kim, Jang Hee Hong, Jin-Gyu Jung, Sun Young Park, Jung Sunwoo","doi":"10.1002/cpdd.1532","DOIUrl":"10.1002/cpdd.1532","url":null,"abstract":"This phase 1, randomized, open-label, 2 × 2 crossover study evaluated the bioequivalence of fixed-dose combination (FDC) formulations of alogliptin (ALO) and metformin extended-release (MET XR) compared to their individual formulations and assessed the effect of food on FDC pharmacokinetics in healthy participants. The study comprised the high-dose bioequivalence study (ALO 25 mg/MET XR 1000 mg) and the low-dose bioequivalence study (ALO 12.5 mg/MET XR 500 mg), both conducted under fasting conditions, and the food effect study (ALO 12.5 mg/MET XR 1000 mg) conducted under both fasting and fed conditions. Among enrolled participants, 46 of 50 completed the high-dose bioequivalence study, 45 of 51 completed the low-dose bioequivalence study, and 22 of 26 completed the food effect study. Plasma concentrations were analyzed using liquid chromatography-tandem mass spectrometry. The geometric mean ratios of AUClast and Cmax for the FDC versus individual formulations were within the bioequivalence range (0.80-1.25) for both ALO and MET XR. ALO's pharmacokinetics were unaffected by food, while MET XR exhibited a significant food effect, with AUClast increasing by a factor of 1.63 and Tmax delayed by 2 hours. Given these findings, the FDC should be administered with food, consistent with MET XR monotherapy recommendations.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 6","pages":"443-451"},"PeriodicalIF":1.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0