Clinical Pharmacology & Therapeutics最新文献

Effectiveness and Safety of Reduced-Dose Prasugrel in an East Asian Population: PRASFIT-ACS Emulation Using National Health Insurance Claims Data. 减少剂量普拉格雷在东亚人群中的有效性和安全性：使用国家健康保险索赔数据的prasit - acs模拟

IF 5.5 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-08-04 DOI: 10.1002/cpt.70017

Li-Wen Huang, Yee-Jen Wu, Fang-Ju Lin, Chien-Chih Wu, Hsin-Yi Huang, Chi-Chuan Wang, Xiaojuan Li

{"title":"Effectiveness and Safety of Reduced-Dose Prasugrel in an East Asian Population: PRASFIT-ACS Emulation Using National Health Insurance Claims Data.","authors":"Li-Wen Huang, Yee-Jen Wu, Fang-Ju Lin, Chien-Chih Wu, Hsin-Yi Huang, Chi-Chuan Wang, Xiaojuan Li","doi":"10.1002/cpt.70017","DOIUrl":"https://doi.org/10.1002/cpt.70017","url":null,"abstract":"Prasugrel is recommended for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, East Asians exhibit a stronger antiplatelet response, raising concerns about bleeding risks with standard dosing. This retrospective cohort study evaluated the real-world effectiveness and safety of reduced-dose prasugrel in an East Asian population by emulating the pivotal PRASFIT-ACS trial using Taiwan's National Health Insurance claims data. In this study, ACS patients were classified into reduced-dose prasugrel or clopidogrel groups post-PCI. We estimated the intention-to-treat effect of initiating reduced-dose prasugrel vs. clopidogrel on the risk of major adverse cardiovascular events (MACE) and the per-protocol effect of treating with reduced-dose prasugrel on major bleeding risk using Cox proportional hazard models. A total of 4833 ACS patients were analyzed, including 977 (20.2%) who received reduced-dose prasugrel. Reduced-dose prasugrel showed comparable effectiveness to clopidogrel in preventing MACE (HR: 0.96, 95% CI: 0.72-1.29) and did not increase bleeding risk (HR: 0.82, 95% CI: 0.36-1.90), consistent with PRASFIT-ACS results (HRMACE: 0.85, 95% CI: 0.62-1.16; HRBleeding: 0.82, 95% CI: 0.39-1.73). A significant reduction in cardiovascular mortality was observed (HR: 0.51, 95% CI: 0.29-0.89), differing from PRASFIT-ACS findings (HR: 1.21, 95% CI: 0.48-3.06). Our results suggest that reduced-dose prasugrel was effective in preventing thrombotic events in the Taiwanese population without significantly increasing bleeding risk. These findings align with pivotal trial outcomes while highlighting the importance of race-specific dose adjustments to optimize ACS treatment strategies. Further research is needed to evaluate whether these results are applicable to other East Asian populations.","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Expediting Drug Development in Japan: A PMDA Perspective. 加速日本药物开发：一个PMDA的视角。

IF 5.5 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-08-04 DOI: 10.1002/cpt.70022

Yoichi Kohno, Akihiro Ishiguro, Takashi Yasukawa, Naoyuki Yasuda, Daisuke Tanaka, Yasuhiro Araki, Yukio Takahashi, Yoshiaki Uyama, Yasuhiro Fujiwara

引用次数: 0

A Hybrid Design Incorporating External Data to Evaluate Dexamethasone Intracameral Drug Delivery Suspension for Post-Cataract Surgery Inflammation. 结合外部数据的混合设计评估地塞米松内窥镜给药暂停治疗白内障手术后炎症。

IF 5.5 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-07-31 DOI: 10.1002/cpt.70010

Yuanyuan Zhao, Keer Chen, Jun Zhou, Jun Zhao, Dingheng Zhang, Junyue Wan, Weihong Yuan, Xi Chen, Ming Tan, Fuqiang Cui, Shein-Chung Chow, Ying Wu

{"title":"A Hybrid Design Incorporating External Data to Evaluate Dexamethasone Intracameral Drug Delivery Suspension for Post-Cataract Surgery Inflammation.","authors":"Yuanyuan Zhao, Keer Chen, Jun Zhou, Jun Zhao, Dingheng Zhang, Junyue Wan, Weihong Yuan, Xi Chen, Ming Tan, Fuqiang Cui, Shein-Chung Chow, Ying Wu","doi":"10.1002/cpt.70010","DOIUrl":"https://doi.org/10.1002/cpt.70010","url":null,"abstract":"Traditional randomized controlled trials (RCTs) face increasing challenges due to lengthy recruitment and high costs. Regulators have encouraged the use of external data and real-world evidence (RWE) to improve efficiency, yet adoption in confirmatory settings remains limited by concerns over heterogeneity and bias. We conducted a proof-of-concept study to assess the feasibility and regulatory value of a hybrid Bayesian borrowing design to support a Phase III RCT of Dexamethasone Intracameral Drug-Delivery Suspension (DEXYCU) in China. Using the Equivalence Probability Propensity Score Meta-Analytic-Predictive (EQPSMAP) approach, we integrated three data sources-a global RCT, a regional Phase III RCT in China, and a real-world data (RWD) in China. The method's performance was evaluated via point estimates and 95% credible intervals for the primary efficacy endpoint. The hybrid design based on EQPSMAP demonstrated greater robustness and accuracy in the presence of baseline imbalances and heterogeneous data. Compared to a traditional RCT, the hybrid design reduced the required sample size by 41 to 158 patients and shortened trial duration by approximately 2 to 5 months while preserving internal validity. This study demonstrated the feasibility and regulatory value of hybrid Bayesian designs in late-phase trials. The approach offers a practical, bias-controlled framework for integrating external data into regional drug development and regulatory decision making.","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The Type of Follicle-Stimulating Hormone Medication Given for In Vitro Fertilization Impacts Oocyte Retrieval: A Systematic Review and Meta-Analysis. 促卵泡激素药物类型对体外受精卵母细胞回收的影响：一项系统综述和荟萃分析。

IF 5.5 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-07-31 DOI: 10.1002/cpt.70014

Toni J F Michael, Ranita Kirubakaran, Tanay Parab, Rui Wang, Mark Grosser, Beverley J Vollenhoven, Vinayak Smith, Sophie L Stocker

{"title":"The Type of Follicle-Stimulating Hormone Medication Given for In Vitro Fertilization Impacts Oocyte Retrieval: A Systematic Review and Meta-Analysis.","authors":"Toni J F Michael, Ranita Kirubakaran, Tanay Parab, Rui Wang, Mark Grosser, Beverley J Vollenhoven, Vinayak Smith, Sophie L Stocker","doi":"10.1002/cpt.70014","DOIUrl":"https://doi.org/10.1002/cpt.70014","url":null,"abstract":"Understanding the variability in ovarian response following administration of follicle-stimulating hormone medications in women undergoing in vitro fertilization may help inform prescribing decisions. A systematic review was conducted to compare the number of retrieved oocytes and fertility outcomes following the administration of different follicle-stimulating hormone medications. Databases were searched from inception to November 2024, including studies that compared two follicle-stimulating hormone medications, including follitropin alfa, follitropin beta, follitropin delta, and urofollitropin. Meta-analyses were performed in random effects models with the restricted maximum likelihood method. From 3867 identified articles, 26 (12613 participants) were included. More oocytes were retrieved with follitropin alfa compared to beta (mean difference 0.64, 95% CI 0.09-1.19). Compared to follitropin delta, more oocytes were retrieved with follitropin alfa and beta (1.38, 95% CI 0.09-2.67, and 1.40, 95% CI 0.41-2.39, respectively); however, higher total doses of follitropin alfa and beta were administered (199.29 IU, 95% CI 43.15-355.43 and 181.08 IU, 95% CI 55.67-306.49, respectively), and the risk of hyperstimulation increased (risk ratios 1.42, 95% CI 1.04-1.96 and 1.75, 95% CI 1.15-2.70, respectively). More oocytes were retrieved with urofollitropin compared to follitropin beta (1.12, 95% CI -1.63 to -0.62), with higher total doses of urofollitropin administered (782.32 IU, 95% CI -1493.79 to -70.85). Variability in ovarian response and hyperstimulation rates across the medications decreased when similar total doses were administered. Fertilization, pregnancy, and live birth rates were similar across the medications, despite differences in the number of retrieved oocytes. Additional research is required to evaluate oocyte quality across follicle-stimulating hormone medications.","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Evidence Generation for Drugs and Biological Products isn't Magic or Myth. 药物和生物制品的证据生成不是魔术或神话。

IF 5.5 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-07-29 DOI: 10.1002/cpt.3570

John Concato, Leonard Sacks, Peter Stein, Jacqueline Corrigan-Curay

引用次数: 0

Risk of Infections with SGLT2 Inhibitors Versus DPP4 Inhibitors: A Population-Based Cohort Study Using Antibiotic Dispensing Data. SGLT2抑制剂与DPP4抑制剂的感染风险：一项基于人群的抗生素分配数据队列研究

IF 6.3 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-07-25 DOI: 10.1002/cpt.70016

Maria J Alfonso Arvez, George S Q Tan, Sam Wade, Zanfina Ademi, Jenni Ilomäki, J Simon Bell

{"title":"Risk of Infections with SGLT2 Inhibitors Versus DPP4 Inhibitors: A Population-Based Cohort Study Using Antibiotic Dispensing Data.","authors":"Maria J Alfonso Arvez, George S Q Tan, Sam Wade, Zanfina Ademi, Jenni Ilomäki, J Simon Bell","doi":"10.1002/cpt.70016","DOIUrl":"https://doi.org/10.1002/cpt.70016","url":null,"abstract":"This study compared the number and cumulative dose of antibiotic dispensings among new users of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors following hospital discharge in individuals with type 2 diabetes. A retrospective cohort study was conducted using data from public and private hospitals in Victoria, Australia. Antibiotic dispensings were assessed over 12 months among new users of these medicines. Negative binomial regression with inverse probability of treatment weighting was applied to estimate weighted incidence rate ratios and confidence intervals for the total number of antibiotic dispensings and cumulative defined daily doses, stratified by antibiotic class. A total of 58.3% of SGLT2 inhibitor users (9,162 individuals) and 61.4% of DPP4 inhibitor users (16,589 individuals) received antibiotics. Initiators of SGLT2 inhibitors had a lower number of overall antibiotic dispensings compared with initiators of DPP4 inhibitors (weighted incidence rate ratio 0.88, 95% confidence interval 0.85 to 0.90), a pattern that was consistent across antibiotic classes. SGLT2 inhibitor initiators also had lower cumulative defined daily doses overall (weighted incidence rate ratio 0.89, 95% confidence interval 0.86 to 0.93), with significantly lower doses for penicillins, sulphonamides, and quinolones. These findings suggest that the initiation of SGLT2 inhibitors was associated with lower antibiotic use in terms of both the number of dispensings and cumulative dose, indicating potentially lower rates of infections among individuals with type 2 diabetes.","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Cytochrome P450 2D6 *17 and *29 Allele Activity for Risperidone Metabolism: Advancing Precision Medicine Health Equity. 细胞色素P450 2D6 *17和*29等位基因活性与利培酮代谢：推进精准医疗健康公平。

IF 6.3 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-07-24 DOI: 10.1002/cpt.70012

Oyinlade Kehinde, Samuel E Vaughn, Ogochukwu Amaeze, Paul Toren, Brandon Retke, Akinyemi Oni-Orisan, Laura B Ramsey

{"title":"Cytochrome P450 2D6 *17 and *29 Allele Activity for Risperidone Metabolism: Advancing Precision Medicine Health Equity.","authors":"Oyinlade Kehinde, Samuel E Vaughn, Ogochukwu Amaeze, Paul Toren, Brandon Retke, Akinyemi Oni-Orisan, Laura B Ramsey","doi":"10.1002/cpt.70012","DOIUrl":"https://doi.org/10.1002/cpt.70012","url":null,"abstract":"CYP2D6 alleles with low frequency in Eurocentrically biased study populations are often excluded from pharmacogenetic investigation and consequently may have misassigned activity values. This health inequity may be contributing to imprecise dose predictions for CYP2D6-metabolizing drugs. The objective of this study was to determine how sub-Saharan African-specific CYP2D6*17 and *29 alleles affect risperidone metabolism. To do this, we generated the largest real-world cohort of risperidone users in an African study population for pharmacogenetic studies. Risperidone users ≤ 18 years old were recruited from the Federal Neuro-Psychiatric Hospital. Health records were obtained by parent report and paper charts. CYP2D6 genotyping was performed for > 20 variants. Plasma concentrations of risperidone and 9-hydroxyrisperidone were determined by liquid chromatography mass spectrometry. CYP2D6 activity was calculated based on the metabolic ratio 9-hydroxyrisperidone:risperidone. Multivariable linear regression modeling was performed to determine the association between our alleles of interest and log-transformed ratio-defined CYP2D6 activity relative to star alleles with established activity values. Across 208 enrolled participants, CYP2D6 activity value for *17 was found to be twice that of normal function alleles, while *29 was comparable to no function alleles. These results contrast previous values assigned to *17 and *29 from guidelines, which are not based on evidence with risperidone, suggesting the possibility of substrate specificity for these alleles. Ultimately, our findings have the potential to improve risperidone prescribing, especially for patient groups with substantial sub-Saharan African ancestry. Importantly, this work underscores the critical need to better understand the effects of ancestry-specific alleles for achieving equitable pharmacotherapeutic health outcomes.","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pediatric Hepatic Impairment Dosing in FDA Approvals Between 2002 and 2024. 2002年至2024年FDA批准的儿童肝功能损害剂量。

IF 6.3 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-07-24 DOI: 10.1002/cpt.70011

Deandra A Cassel, Gilbert J Burckart, Martina D Sahre, Gelareh A Abulwerdi

{"title":"Pediatric Hepatic Impairment Dosing in FDA Approvals Between 2002 and 2024.","authors":"Deandra A Cassel, Gilbert J Burckart, Martina D Sahre, Gelareh A Abulwerdi","doi":"10.1002/cpt.70011","DOIUrl":"https://doi.org/10.1002/cpt.70011","url":null,"abstract":"The safety and efficacy of drugs metabolized by the liver can be substantially impacted by alterations in hepatic function. However, hepatic impairment (HI) is rarely evaluated in pediatric drug development due to challenges such as the relatively small number of patients, differences in adult and pediatric liver disease, and the lack of agreed-upon markers to assess HI severity. The objectives of the study were to (1) examine adult and pediatric HI dosing recommendations in US FDA prescribing information (PI) and pediatric dosing handbooks, Lexicomp and Micromedex, and (2) identify the clinical evidence behind HI dosing recommendations for pediatric patients. A total of 61 drugs containing both a pediatric indication and the word \"hepatic\" in the Dosage and Administration section of the PI were reviewed. Of the 61 drugs, only eight drugs included pediatric-specific HI dosing recommendations, with seven based on the Child-Pugh classification. Pharmacokinetic studies in adults with HI were the primary evidence behind the recommendations for all eight drugs, and only one drug was evaluated in pediatric patients with mild HI. Lexicomp and Micromedex provided consistent HI dosing recommendations with the PI and did not cite additional evidence. Overall, there is a gap in dosing recommendations for pediatric patients with HI. Alternative approaches, such as modeling and simulation based on drug- and disease-specific parameters, may help address knowledge gaps for pediatric patients with HI in the future.","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

IF 6.3 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-07-24 DOI: 10.1002/cpt.70004

Jue Gong, Jie Zhou, Dongfen Yuan, Xuewen Ma, Deeksha Vishwamitra, Brandi Hilder, Tara J Masterson, Jaszianne Tolbert, Thomas Renaud, Christoph Heuck, Colleen Kane, Mahesh N Samtani, Suzette Girgis, Nahor Haddish-Berhane, Jesus Berdeja, Amrita Krishnan, Daniele Ouellet

{"title":"Recommended Phase II Doses of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma From MonumenTAL-1: Clinical Pharmacology Results.","authors":"Jue Gong, Jie Zhou, Dongfen Yuan, Xuewen Ma, Deeksha Vishwamitra, Brandi Hilder, Tara J Masterson, Jaszianne Tolbert, Thomas Renaud, Christoph Heuck, Colleen Kane, Mahesh N Samtani, Suzette Girgis, Nahor Haddish-Berhane, Jesus Berdeja, Amrita Krishnan, Daniele Ouellet","doi":"10.1002/cpt.70004","DOIUrl":"https://doi.org/10.1002/cpt.70004","url":null,"abstract":"Talquetamab is the first and only GPRC5D × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). In the phase I/II MonumenTAL-1 study, overall response rates (ORRs) were > 66% in patients with RRMM treated with subcutaneous talquetamab at the recommended phase II doses (RP2Ds): 0.4 mg/kg weekly and 0.8 mg/kg every other week. We characterized the pharmacokinetics (PK), pharmacodynamics, immunogenicity, and exposure-response relationships for efficacy and safety following talquetamab administration in phase I and II. In phase I, talquetamab exposure increased in an approximately dose-proportional manner across intravenous and subcutaneous doses and was maintained around or above the 90% maximum effective concentration identified in an ex vivo cytotoxic assay at the RP2Ds. Higher levels of T-cell activation and cytokine induction were observed at the RP2Ds compared with lower doses. Talquetamab demonstrated time-dependent clearance with a half-life of 7.56 days at initial treatment and 12.2 days at steady state. Patients with immunoglobulin G multiple myeloma and International Staging System (ISS) stage II/III exhibited higher clearance of talquetamab, which resulted in lower exposure. Dose adjustment based on myeloma subtype and ISS stage was not required. In exposure-response analyses, a near-flat relationship was demonstrated for ORR, duration of response, and progression-free survival at the exposure range of the RP2Ds. In safety exposure-response analyses, rates of grade 1/2 dysgeusia increased with higher exposures. The incidence of anti-talquetamab antibodies had no apparent impact on the PK, efficacy, or safety of talquetamab. These clinical pharmacology results support the selection of the talquetamab RP2Ds.","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Advancing Early Clinical Trials: The Transformative Potential of Decentralized Designs and Digital Technologies in Phase 1 Clinical Trial. 推进早期临床试验：分散设计和数字技术在1期临床试验中的变革潜力。

IF 6.3 2区医学

Clinical Pharmacology & Therapeutics Pub Date : 2025-07-24 DOI: 10.1002/cpt.70002

Bimal K Malhotra, Josué Kunjom Mfopou, Isabelle Huyghe, Pascal Ryckmans, Nathalie Severs, Anna Plotka, Kim-Claire Tabner, Malgorzata Anna Jennes, Anand Bhuvanendran Nair, Anna Colzi

{"title":"Advancing Early Clinical Trials: The Transformative Potential of Decentralized Designs and Digital Technologies in Phase 1 Clinical Trial.","authors":"Bimal K Malhotra, Josué Kunjom Mfopou, Isabelle Huyghe, Pascal Ryckmans, Nathalie Severs, Anna Plotka, Kim-Claire Tabner, Malgorzata Anna Jennes, Anand Bhuvanendran Nair, Anna Colzi","doi":"10.1002/cpt.70002","DOIUrl":"https://doi.org/10.1002/cpt.70002","url":null,"abstract":"A Phase 1, open-label, single-dose, fixed-sequence crossover study utilizing a hybrid decentralized clinical trial (DCT) design with and without practice sessions for wearable devices and PK sampling was conducted in eight healthy participants. Using etrasimod, the study assessed the feasibility of conducting a Phase 1 hybrid DCT by the Pfizer Clinical Research Unit (PCRU) staff, involving remote collection of pharmacokinetic (PK), safety, and tolerability data. The study objectives were to determine the PK and to assess the safety and tolerability of etrasimod clinical immediate release tablets in healthy adult participants in a hybrid DCT design. The study consisted of two periods, and the treatments were administered to participants in a fixed sequence: a single oral dose of etrasimod, then DCT with practice sessions in Period 1, followed by a single oral dose of etrasimod and DCT without practice sessions in Period 2. PK results were compared between Periods 1 and 2, and vs. PK from a single oral dose of etrasimod administered on site in a previous conventional design study. Serum etrasimod exposure was similar for non-practice vs. practice sessions within the hybrid DCT framework. PK parameters data from self-collected microsamples in the hybrid DCT design were comparable to PK parameters data from venous samples collected in a conventional setting. The wearable monitoring devices for recording the electrocardiogram (ECG) and vital parameters allowed remote and real-time assessment of safety and tolerability. Therefore, the study results demonstrated the feasibility of using multiple DCT modalities in Phase 1 trials for remote PK, safety, and tolerability assessments.","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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