Clinical Pharmacology in Drug Development最新文献_第4页

Population Pharmacokinetics Modeling and Simulation of Deutenzalutamide, A Novel Androgen Receptor Antagonist, in Patients With Metastatic Castration-Resistant Prostate Cancer 新型雄激素受体拮抗剂 Deutenzalutamide 在转移性抗性前列腺癌患者中的群体药代动力学建模与模拟。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-04 DOI: 10.1002/cpdd.1477

Yixian Liu, Yongji He, Xiaohui Qi, Xinghai Li, Yi Zhou, Yuanwei Chen, Zhenlei Wang, Li Zheng

{"title":"Population Pharmacokinetics Modeling and Simulation of Deutenzalutamide, A Novel Androgen Receptor Antagonist, in Patients With Metastatic Castration-Resistant Prostate Cancer","authors":"Yixian Liu, Yongji He, Xiaohui Qi, Xinghai Li, Yi Zhou, Yuanwei Chen, Zhenlei Wang, Li Zheng","doi":"10.1002/cpdd.1477","DOIUrl":"10.1002/cpdd.1477","url":null,"abstract":"Deutenzalutamide is a new molecular entity androgen receptor antagonist. The primary aim of this study was to develop a population pharmacokinetic model of deutenzalutamide and evaluate effects of intrinsic and extrinsic factors on pharmacokinetics. A nonlinear mixed-effects modeling approach was performed to develop the population pharmacokinetic of deutenzalutamide using data from 1 Phase I trial of deutenzalutamide. Goodness-of-fit plots, prediction-corrected visual predictive check, and bootstrap analysis were carried out to evaluate the final model. Simulation for the developed model was used to evaluate the covariate effects on the pharmacokinetics of deutenzalutamide. A 2-compartment model with first-order absorption and elimination from the central compartment was established for deutenzalutamide. The final covariate included body weight on peripheral compartment volume. This is the first research developing the population pharmacokinetic model of deutenzalutamide in patients with metastatic castration-resistant prostate cancer, and it is expected to support the future clinical administration of deutenzalutamide.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1291-1300"},"PeriodicalIF":1.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371181","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

Phase 1 Evaluation of the Bioequivalence and Drug-Drug Interaction Potential of a Novel Fixed-Dose Combination of Ezetimibe, Atorvastatin, and Amlodipine 对依折麦布、阿托伐他汀和氨氯地平的新型固定剂量复方制剂的生物等效性和药物相互作用潜力的第一阶段评估

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-27 DOI: 10.1002/cpdd.1472

Hyung Soon Lim, Jae Hoon Kim, Jang Hee Hong, Jin-Gyu Jung, Jung Sunwoo

{"title":"Phase 1 Evaluation of the Bioequivalence and Drug-Drug Interaction Potential of a Novel Fixed-Dose Combination of Ezetimibe, Atorvastatin, and Amlodipine","authors":"Hyung Soon Lim, Jae Hoon Kim, Jang Hee Hong, Jin-Gyu Jung, Jung Sunwoo","doi":"10.1002/cpdd.1472","DOIUrl":"10.1002/cpdd.1472","url":null,"abstract":"A fixed-dose combination (FDC) of ezetimibe, atorvastatin, and amlodipine has been developed to improve medication adherence among patients with cardiovascular diseases. In a randomized, open-label, multiple-dose, fixed-sequence study involving 34 participants (Study 1), the potential drug-drug interaction between ezetimibe/atorvastatin FDC and amlodipine was evaluated. Additionally, a randomized, open-label, crossover study with 60 participants (Study 2) compared the pharmacokinetics (PKs) of ezetimibe/atorvastatin/amlodipine FDC to those of individual formulations. Co-administration of the ezetimibe/atorvastatin FDC and amlodipine did not significantly alter the PKs of either drug. However, amlodipine resulted in a slight increase in systemic exposure to atorvastatin by approximately 23%. Geometric mean ratios (FDC to individual formulations) and 90% confidence intervals of area under the time-concentration curve at steady state during dosing interval (AUCτ, ss) and maximum concentration at steady state (Cmax, ss) or amlodipine, atorvastatin, and ezetimibe were all within the bioequivalent range (0.8-1.25), confirming bioequivalence. Moreover, the FDC of ezetimibe, atorvastatin, and amlodipine exhibited comparable tolerability to corresponding individual formulations.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1345-1354"},"PeriodicalIF":1.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343021","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

Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Pritelivir and Its Metabolites 肾功能和肝功能受损对普利特韦及其代谢物药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-25 DOI: 10.1002/cpdd.1469

Katharina Erb-Zohar, Susanne Bonsmann, Jörg Pausch, Melanie Sumner, Alexander Birkmann, Holger Zimmermann, Atef Halabi, Dirk Kropeit

{"title":"Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Pritelivir and Its Metabolites","authors":"Katharina Erb-Zohar, Susanne Bonsmann, Jörg Pausch, Melanie Sumner, Alexander Birkmann, Holger Zimmermann, Atef Halabi, Dirk Kropeit","doi":"10.1002/cpdd.1469","DOIUrl":"10.1002/cpdd.1469","url":null,"abstract":"Two trials were performed to evaluate the effect of renal and hepatic impairment on the pharmacokinetics of pritelivir and its metabolites. The renal impairment trial included subjects with mild, moderate, and severe impairment, while the hepatic impairment trial included subjects with moderate impairment. Both trials recruited a matched control group of healthy subjects. Following a single oral dose of 100 mg of pritelivir, mild and moderate renal impairment and moderate hepatic impairment did not have a clinically relevant effect on the pharmacokinetics of pritelivir. In subjects with severe renal impairment, pritelivir exposure (area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) was 57% higher compared with controls. Pritelivir plasma protein binding was similar in subjects and controls with renal impairment, while the free fraction was higher in subjects with moderate hepatic impairment, increasing unbound pritelivir exposure by 23%. For the metabolites pyridinyl phenyl acetic acid (PPA), amino thiazole sulfonamide (ATS), and PPA-acyl glucuronide, generally higher exposure was observed with increasing degree of renal impairment (ie, moderate to severe), but not with mild impairment. A modest effect of moderate hepatic impairment was observed for PPA and ATS. Pritelivir was safe and well tolerated in healthy subjects and subjects with renal or hepatic impairment.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1198-1211"},"PeriodicalIF":1.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343020","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 of Subcutaneous Itepekimab Injection With an Autoinjector Device and Prefilled Syringe in Healthy Participants 使用自动注射器装置和预灌封注射器皮下注射伊替匹单抗的药代动力学

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-23 DOI: 10.1002/cpdd.1466

Christine Xu, Kong Xin, Matthew P. Kosloski, Allison Butler, Helene Goulaouic, Michael C. Nivens, Vanaja Kanamaluru

{"title":"Pharmacokinetics of Subcutaneous Itepekimab Injection With an Autoinjector Device and Prefilled Syringe in Healthy Participants","authors":"Christine Xu, Kong Xin, Matthew P. Kosloski, Allison Butler, Helene Goulaouic, Michael C. Nivens, Vanaja Kanamaluru","doi":"10.1002/cpdd.1466","DOIUrl":"10.1002/cpdd.1466","url":null,"abstract":"Itepekimab, a monoclonal antibody against interleukin-33, has demonstrated clinical utility in previous studies in patients with asthma and chronic obstructive pulmonary disease. An autoinjector (AI) has been developed for administering itepekimab to facilitate further development. This study compared pharmacokinetics of single 300-mg itepekimab subcutaneous administration via an AI versus a prefilled syringe (PFS). Of 90 healthy volunteers enrolled in this Phase 1, parallel-design, randomized study and stratified by body weight (50 to <70 kg, ≥70 to <80 kg, ≥80 to 100 kg) and injection site (abdomen, thigh, or arm), 84 completed the study. Systemic exposure of itepekimab was similar for both groups. Point estimates for geometric mean ratios of pharmacokinetic parameters for AI versus PFS groups were 1.01 for maximum serum concentration, 1.06 for area under the serum concentration-time curve to the last quantifiable concentration, and 1.04 for area under the serum concentration-time curve extrapolated to infinity. The exposure was similar for both devices in each body weight and injection site subgroup. Overall, systemic exposure of 300-mg single-dose itepekimab in healthy participants was comparable when administered subcutaneously via an AI device and PFS, with an acceptable safety profile in both device groups.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1181-1188"},"PeriodicalIF":1.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281401","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

New Ustekinumab Biosimilar Candidate FYB202: Pharmacokinetic Equivalence Demonstrated in a Randomized, Double-Blind, Parallel-Group, Single-Dose Trial in Healthy Subjects 新型 Ustekinumab 生物仿制药 FYB202：在健康受试者中进行的一项随机、双盲、平行组、单剂量试验证明了其药代动力学等效性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-19 DOI: 10.1002/cpdd.1473

Sigrid Balser, Katrin Nopora, Juliane Körner, Ralph-Steven Wedemeyer, Maria Anschütz, Barbara Schug

{"title":"New Ustekinumab Biosimilar Candidate FYB202: Pharmacokinetic Equivalence Demonstrated in a Randomized, Double-Blind, Parallel-Group, Single-Dose Trial in Healthy Subjects","authors":"Sigrid Balser, Katrin Nopora, Juliane Körner, Ralph-Steven Wedemeyer, Maria Anschütz, Barbara Schug","doi":"10.1002/cpdd.1473","DOIUrl":"10.1002/cpdd.1473","url":null,"abstract":"In the RUSTIC trial, pharmacokinetic (PK) similarity between the proposed ustekinumab biosimilar FYB202 and EU-approved (EU-Ref) and US-licensed ustekinumab (US-Ref) as well as between both reference drugs was assessed after a single 45-mg subcutaneous injection. Safety analyses comprised immunogenicity (antidrug antibodies, neutralizing antibodies), adverse events, and local tolerability. Overall, 491 healthy adults were randomized 1:1:1 and observed for up to 112 days; 486 completed the trial, and 478 were included in the PK analysis. All 3 comparisons showed PK similarity, since the 90% confidence intervals of the respective geometric mean ratios for area under the concentration-time curve from time 0 to infinity and maximum serum concentration were contained within the acceptance interval of 80%-125%. No clinically meaningful differences regarding overall safety, immunogenicity, and local tolerability were observed. Notably, after FYB202 administration, in fewer subjects at least 1 positive antidrug antibody result was observed compared to the reference groups (FYB202, 20%; EU-Ref, 42%; US-Ref, 51%). In conclusion, the RUSTIC trial demonstrated equivalent PK characteristics for FYB202 when compared to both EU-Ref and US-Ref ustekinumab and between both reference drugs. It provides the basis for the marketing authorization of FYB202, together with an extensive analytical characterization and the results of a confirmatory efficacy and safety trial in patients with moderate to severe plaque psoriasis.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1308-1316"},"PeriodicalIF":1.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281400","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

A Phase 1, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Bepirovirsen in Adults with Hepatic Impairment and Healthy Participants (B-Assured) 评估肝功能受损成人和健康参与者服用贝吡罗韦森的药代动力学和安全性的单剂量 1 期研究 (B-Assured)

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-13 DOI: 10.1002/cpdd.1454

Nadia Noormohamed, Tamara Lukic, Thomas C. Marbury, Eric J. Lawitz, Holly Prescott, Mindy Magee, Ahmed Nader, Kelong Han

{"title":"A Phase 1, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Bepirovirsen in Adults with Hepatic Impairment and Healthy Participants (B-Assured)","authors":"Nadia Noormohamed, Tamara Lukic, Thomas C. Marbury, Eric J. Lawitz, Holly Prescott, Mindy Magee, Ahmed Nader, Kelong Han","doi":"10.1002/cpdd.1454","DOIUrl":"10.1002/cpdd.1454","url":null,"abstract":"Bepirovirsen is a developmental antisense oligonucleotide (ASO) for treatment of chronic hepatitis B virus infection. No pharmacokinetic (PK) studies comparing participants with hepatic impairment (HI) and healthy participants (HPs) have been conducted with ASOs. Given the target patient population, characterization of bepirovirsen PK in HI was imperative. This phase 1, nonrandomized, open-label study (NCT04971928) evaluated the PKs of a single 300-mg dose of bepirovirsen in participants with HI and matched HPs, enrolled in 2 parts (Part 1: moderate HI; Part 2: mild HI). If no predefined difference in the area under the concentration-time curve from time 0 (predose) to infinite time (AUC0-∞) and maximum observed concentration (Cmax; geometric mean ratio [GMR] 0.5-1.5) was identified in Part 1, findings were applied to mild HI, eliminating Part 2. Participants were monitored for 50 days post-treatment and noncompartmental analysis estimated PK parameters. Twenty-four participants (moderate HI, n = 12; HP, n = 12) received bepirovirsen and completed Part 1. AUC0-∞ and Cmax were lower in participants with moderate HI (GMR 0.69 and 0.67, respectively) than in HPs, while apparent clearance (CL/F) and apparent terminal phase volume of distribution (Vz/F) were higher (GMR 1.44 and 1.64, respectively), but fell within the predefined thresholds of difference for this study. Part 2 was omitted. Adverse events were mild. Moderate HI did not have a clinically relevant impact on bepirovirsen PK or safety.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1088-1097"},"PeriodicalIF":1.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250495","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 Bioequivalence of a Generic Ticagrelor 90‐mg Formulation Versus the Innovator Product in Healthy White Subjects Under Fasting Conditions 在空腹条件下，仿制药替卡格雷 90 毫克制剂与创新产品在健康白人受试者中的药代动力学和生物等效性研究

IF 2 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-11 DOI: 10.1002/cpdd.1471

Simona Rizea‐Savu, Simona Nicoleta Duna, Adrian Ghita, Adriana Iordachescu, Ioana Garlea, Marinela Chirila

{"title":"Pharmacokinetics and Bioequivalence of a Generic Ticagrelor 90‐mg Formulation Versus the Innovator Product in Healthy White Subjects Under Fasting Conditions","authors":"Simona Rizea‐Savu, Simona Nicoleta Duna, Adrian Ghita, Adriana Iordachescu, Ioana Garlea, Marinela Chirila","doi":"10.1002/cpdd.1471","DOIUrl":"https://doi.org/10.1002/cpdd.1471","url":null,"abstract":"Ticagrelor is a key antiplatelet agent used to prevent thrombotic events in patients with acute coronary syndrome. This open‐label, 2‐period, crossover Phase I study assessed the pharmacokinetics and bioequivalence of a generic ticagrelor 90‐mg formulation compared to the innovator product under fasting conditions. Twenty‐eight healthy White adults participated in the study. Each participant received a single dose of either the test or reference formulation, followed by a 7‐day washout period before switching to the alternate formulation. Plasma concentrations of ticagrelor were measured using a validated high‐performance liquid chromatography‐tandem mass spectrometry method. Statistical analysis of primary pharmacokinetic parameters, including maximum concentration and area under the plasma concentration‐time curve from time 0 to the last quantifiable concentration, showed bioequivalence with test/reference ratios of 110.9% and 107.1%, respectively, and 90% confidence intervals within the 80%‐125% regulatory range. Treatment‐emergent adverse events, such as headache, dysphagia, and dizziness, were moderate and transient and resolved promptly, with no significant difference in incidence between the formulations. These results confirm that the generic ticagrelor formulation is bioequivalent to the innovator product, supporting its use as an interchangeable option in clinical practice.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"116 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175806","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 Bioequivalence Trial of Lenvatinib Mesylate Capsules in Healthy Subjects Under Fasting and Postprandial Conditions 健康受试者在空腹和餐后条件下服用甲磺酸伦伐替尼胶囊的生物等效性试验

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-10 DOI: 10.1002/cpdd.1470

Junbo Shao, Xingxing Liu, Geying Zhang, Ajun Xiang, Xiaoyan Xie

{"title":"A Bioequivalence Trial of Lenvatinib Mesylate Capsules in Healthy Subjects Under Fasting and Postprandial Conditions","authors":"Junbo Shao, Xingxing Liu, Geying Zhang, Ajun Xiang, Xiaoyan Xie","doi":"10.1002/cpdd.1470","DOIUrl":"10.1002/cpdd.1470","url":null,"abstract":"The aim of this study was to evaluate the comparative effectiveness and safety profiles of generic lenvatinib mesylate capsules and the reference product in a cohort of healthy Chinese individuals. The research design consisted of a randomized, open-label trial with a single-dose regimen, 2 crossover periods, and 2 distinct phases involving participants from the Chinese population. A total of 24 individuals were enrolled in the fasting study, with an additional 27 participants included in the postmeal study. Each participant received a single dose of either 4 mg of the reference product or the study product per cycle. The washout period was 14 days between each period. Bioequivalence was assessed through the analysis of geometric mean and ratio of pharmacokinetic parameters, while the safety of both drugs was evaluated by monitoring adverse events (AEs). Following a single oral administration of lenvatinib (4 mg), linear pharmacokinetics were observed. The rate of absorption was found to be significantly faster under fasting conditions (median time to maximum concentration, 2.3-2.5 hours), while the presence of a high-fat diet resulted in delayed absorption (median tmax, 5.3-6.1 hours). Furthermore, the 90% confidence intervals for the reference and test pharmacokinetic parameters under both fasting and postprandial conditions fell within the bioequivalence standard range of 80%-125%. AEs were reported in 34.78% of cases during fasting and in 48.15% of cases after eating. There was no significant difference in AE rates between the reference and study products. The study determined that both the study product and the reference product were bioequivalent and well tolerated by healthy Chinese participants in both fasting and postprandial conditions.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1324-1330"},"PeriodicalIF":1.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175807","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 of Meloxicam Nanocrystal Injection in Healthy Chinese Volunteers 美洛昔康纳米晶注射液在中国健康志愿者中的生物等效性研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-05 DOI: 10.1002/cpdd.1467

Shengling Hu, Xia Liu, Qinghua Wan, Xueyuan Zhang, Fengyun Gong

{"title":"Bioequivalence of Meloxicam Nanocrystal Injection in Healthy Chinese Volunteers","authors":"Shengling Hu, Xia Liu, Qinghua Wan, Xueyuan Zhang, Fengyun Gong","doi":"10.1002/cpdd.1467","DOIUrl":"10.1002/cpdd.1467","url":null,"abstract":"This single-center, randomized, open, two-preparation, single-dose, two-period, self-crossover trial aimed to assess the bioequivalence and safety of the test (T) preparation compared to the reference (R) preparation following intravenous injection in healthy subjects under fasting conditions. Twenty-four healthy subjects were enrolled in the study and subjects were randomly divided into two groups at a 1:1 ratio and were administered once per period, with an 8-day washout period. During each period, serum drug concentrations were detected for pharmacokinetic analysis and adverse events were recorded for safety analysis. The 90% confidence intervals for the geometric mean ratios (T:R) of maximum serum concentration, area under the serum concentration-time curve from time zero to the last measurable concentration, and area under the serum concentration-time curve from time zero to infinite time fell within the predefined bioequivalence range of 80%-125%, indicating bioequivalence between the T and R preparation under fasting conditions. Additionally, four subjects (16.7%) experienced five instances of adverse events in the T group, while five subjects (21.7%) experienced five instances of adverse events in the R group. This trial indicated the potential bioequivalence between the T and R products under fasting conditions, based on pharmacokinetic and safety profile.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1339-1344"},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132068","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

Safety and Pharmacokinetics of Single-Dose Mirikizumab in Chinese Healthy Participants: Results From a Phase 1 Study 单剂量米利珠单抗在中国健康参与者中的安全性和药代动力学：一期研究结果

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-04 DOI: 10.1002/cpdd.1449

Junyu Xu, Ran Xie, Yongjia Ji, Chenxi Qian, Xin Zhang, Kris Todd, Feng Wang, Yimin Cui

{"title":"Safety and Pharmacokinetics of Single-Dose Mirikizumab in Chinese Healthy Participants: Results From a Phase 1 Study","authors":"Junyu Xu, Ran Xie, Yongjia Ji, Chenxi Qian, Xin Zhang, Kris Todd, Feng Wang, Yimin Cui","doi":"10.1002/cpdd.1449","DOIUrl":"10.1002/cpdd.1449","url":null,"abstract":"The objective of this phase 1 single-dose study was to evaluate the safety, tolerability, and pharmacokinetics of mirikizumab in Chinese healthy adults. Sixty participants were randomized within 5 planned dose cohorts: intravenous (IV) 300 mg, IV 600 mg, IV 1200 mg, subcutaneous (SC) 200 mg, and SC 400 mg to receive mirikizumab (10 participants in each cohort) or placebo (2 participants in each cohort). No death or serious adverse events occurred. Twenty-eight (56.0%) participants who received mirikizumab reported 49 treatment-emergent adverse events (TEAEs) and 8 (80.0%) participants who received placebo reported 18 TEAEs. The majority of TEAEs were mild in severity. Following IV 300-1200 mg mirikizumab, the arithmetic mean of both area under the concentration versus time curve from time 0 to infinity (AUC0-∞) and maximum observed drug concentration (Cmax) increased by approximately 3.5-fold, and the arithmetic mean half-life (t1/2) ranged from 9.64 to 12.0 days. Following SC 200 and 400 mg mirikizumab, the arithmetic mean of both AUC0-∞ and Cmax increased by approximately 1.6-fold, the median time to Cmax (tmax) was 2.98 days for both, and the arithmetic mean t1/2 was 10.6 and 10.5 days, respectively. Absolute bioavailability based on pooled SC and IV dose data was 38.2%. In this study, the safety and pharmacokinetic profile of mirikizumab were consistent with what has been reported in other studies.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1143-1150"},"PeriodicalIF":1.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125075","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