Clinical Pharmacology in Drug Development最新文献_第6页

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

Safety, Tolerability, and Pharmacokinetic Profile of the Low-Impact Ampakine CX1739 in Young Healthy Volunteers 年轻健康志愿者服用低冲击安帕金 CX1739 的安全性、耐受性和药代动力学特征

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-20 DOI: 10.1002/cpdd.1475

Daniel P. Radin, Rok Cerne, Jeffrey M. Witkin, Arnold Lippa

{"title":"Safety, Tolerability, and Pharmacokinetic Profile of the Low-Impact Ampakine CX1739 in Young Healthy Volunteers","authors":"Daniel P. Radin, Rok Cerne, Jeffrey M. Witkin, Arnold Lippa","doi":"10.1002/cpdd.1475","DOIUrl":"10.1002/cpdd.1475","url":null,"abstract":"AMPA-type glutamate receptors (AMPARs) mediate the majority of fast excitatory synaptic transmission in the mammalian brain. Ampakines, positive allosteric modulators of AMPAR, hold significant potential for the treatment of a wide range of neurological/neuropsychiatric disorders in which excitatory synaptic transmission is compromised. Low-impact ampakines are a distinct subset of ampakines that accelerate channel opening yet minimally affect receptor desensitization, which may explain their lack of seizurogenic effects at therapeutic doses in preclinical models. CX1739 is a low-impact ampakine that has shown efficacy in preclinical studies. The current clinical study examined the tolerability and pharmacokinetics of CX1739 in healthy male volunteers in a 2-part study. Part A was a single dose escalation study (100-1200 mg, 48 patients) and Part B was a multiple dose ascending study (300-600 mg BID for 7-10 days, 32 patients). CX1739 was well tolerated up to 900 mg once daily (QD) and 450 mg twice a day, with the prominent side effects being headache and nausea. Importantly, the half-life of CX1739 was 6-9 hours, and Tmax was 1-5 hours. CX1739 Cmax and AUC were dose-proportional. These findings thus set the stage for further explorations of this drug candidate in phase 2 clinical studies.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"50-58"},"PeriodicalIF":1.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281402","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

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 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-10 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":"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":"14 1","pages":"59-64"},"PeriodicalIF":1.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1471","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":"OA","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

Relative Bioavailability of Sotorasib Following Administration as a Water Dispersion to Healthy Subjects and Compatibility With Enteral Administration 健康受试者服用水分散液后索托拉西布的相对生物利用度以及与肠内给药的兼容性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-04 DOI: 10.1002/cpdd.1468

Panli Cardona, Marintan Spring, Jiemin Bao, Yong Xie, Brett Houk

{"title":"Relative Bioavailability of Sotorasib Following Administration as a Water Dispersion to Healthy Subjects and Compatibility With Enteral Administration","authors":"Panli Cardona, Marintan Spring, Jiemin Bao, Yong Xie, Brett Houk","doi":"10.1002/cpdd.1468","DOIUrl":"10.1002/cpdd.1468","url":null,"abstract":"Sotorasib is approved to be taken as 960 mg orally once daily (8 × 120-mg tablets) for the treatment of KRAS G12C-mutated nonsmall cell lung cancer. Dispersion of tablets in water could be an alternative method for patients who require a liquid formulation due to dysphagia and enteral administration. A clinical study was conducted to assess the pharmacokinetics of 960 mg of sotorasib administered as tablets and as tablets dispersed in water in healthy volunteers. Each subject received 960 mg of sotorasib by mouth, as tablets and as tablets dispersed in water on Days 1 and 4. Sotorasib median time to maximum observed plasma concentration was similar when administered as tablets and as tablets predispersed in water. The geometric least squares mean ratios (water dispersion/tablets) for area under the concentration-time curve from time 0 extrapolated to infinity and maximum observed plasma concentration were 1.049 and 1.080, respectively. Sotorasib 960 mg was well tolerated. Administration of 960 mg of sotorasib as tablets predispersed in water achieved similar systemic exposures to that of sotorasib administered as oral tablets. In vitro evaluations were performed to assess the feasibility of administering sotorasib through an enteral feeding tube. Approximately 98% of sotorasib was recovered, with no new impurities, from enteral feeding tubes. Collectively, these results support that sotorasib can be administered by mouth and via enteral feeding tubes as tablets predispersed in water.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"44-49"},"PeriodicalIF":1.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125074","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

2024 CPDD Abstract Booklet 2024 年美国临床药理学学院年会®。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-01 DOI: 10.1002/cpdd.1459

引用次数: 0