Clinical Drug Investigation最新文献

{"title":"Summary of Research: Comparable Efficacy and Safety of Brodalumab in Obese and Nonobese Patients with Psoriasis: Analysis of Two Randomized Controlled Trials.","authors":"Sylvia Hsu, Lawrence J Green, Mark G Lebwohl, Abby A Jacobson","doi":"10.1007/s40261-025-01423-0","DOIUrl":"https://doi.org/10.1007/s40261-025-01423-0","url":null,"abstract":"<p><p>Obesity is associated with increased psoriasis severity and reduced effectiveness of psoriasis treatments. This is a summary of a research article that reports a study evaluating the efficacy and safety of brodalumab (a subcutaneous injectable therapy) in participants with and without obesity who have moderate-to-severe psoriasis. Data were analyzed from two large, phase 3 clinical trials (AMAGINE-2 and AMAGINE-3) of participants with psoriasis who were treated with brodalumab or another subcutaneous injectable therapy, ustekinumab. After brodalumab treatment for 52 weeks, participants with obesity experienced similar rates of skin clearance to those without obesity (90% improvement: 88% versus 85%; 100% improvement: 65% versus 73%, respectively). Brodalumab safety profiles were generally similar between participants with and without obesity. This study demonstrated that brodalumab is effective and safe for treating moderate-to-severe psoriasis, regardless of obesity status.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview of Isavuconazole Clinical Use: A Multicentre Analysis of Indications, Exposure and Hepatic Safety.","authors":"Anne-Lise Bienvenu, Alexandra Duffour, Claire Chatron, Natacha Mrozek, Luc Foroni, Aurélien Millet, Anne-Claire Lukaszewicz, Claire Merveilleux-du-Vignaux, Philippe Portran, François Parant, Thierry Vial, Hélène Labussière-Wallet, Cécile Moluçon-Chabrot, Pauline Rascle, Agnès Henry, Pierre Pradat, Sylvain Goutelle","doi":"10.1007/s40261-025-01432-z","DOIUrl":"https://doi.org/10.1007/s40261-025-01432-z","url":null,"abstract":"<p><strong>Background: </strong>Isavuconazole is a recent broad-spectrum triazole indicated for the treatment of invasive aspergillosis and mucormycosis when amphotericin B is inappropriate. However, limited information exists on its clinical use.</p><p><strong>Objective: </strong>We set up a retrospective multicentre study to describe the clinical practice of isavuconazole including indications, exposure, and hepatic safety.</p><p><strong>Methods: </strong>From January 2021 to June 2023, all patients who received isavuconazole and had at least one therapeutic drug monitoring (TDM) measurement, were included. To identify independent predictors of isavuconazole trough concentrations (C_min), linear regression analyses were performed. Causal relationship between the occurrence of liver injury and isavuconazole was also analysed.</p><p><strong>Results: </strong>Most of the included patients (n = 102) were admitted into haematology units (41.1% [n = 42]) or intensive care units (ICU) (30.4% [n = 31]). Aspergillosis (47.0% [n = 48]), mucormycosis (25.6% [n = 26]), and off-label empirical treatments (18.6% [n = 19]), were the three most common indications. About half of the patients (46.1% [n = 47]) had an optimal exposure, while 42.2% (n = 43) were underexposed, and 11.7% (n = 12) were overexposed. Albumin level on the day of TDM was a significant factor associated with an increase in isavuconazole C_min (p = 0.010). Among the 11 patients who had liver test abnormalities, isavuconazole was discontinued in six (n = 6) patients and liver injury was attributable to isavuconazole in two (n = 2) patients.</p><p><strong>Conclusions: </strong>This multicentre analysis highlighted the common use of isavuconazole as an off-label indication, as well as the frequent underexposure of patients to isavuconazole. Albumin on the day of TDM appeared to be an important factor driving isavuconazole exposure, especially in ICU patients.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reporting Quality in Health Economic Evaluation Studies of Immune Checkpoint Inhibitors: A Systematic Review.","authors":"Takashi Yoshioka, Shintaro Azuma, Satoshi Funada, Takahiro Itaya, Rei Goto","doi":"10.1007/s40261-025-01435-w","DOIUrl":"https://doi.org/10.1007/s40261-025-01435-w","url":null,"abstract":"<p><strong>Background and objective: </strong>The introduction of immune checkpoint inhibitors (ICIs) in oncology presents a critical healthcare policy challenge for resource allocation due to their substantial financial burden. This study assessed the reporting quality of health economic evaluation (HEE) studies of ICIs.</p><p><strong>Methods: </strong>This study conducted a systematic literature search of four databases (PubMed, EMBASE, Cochrane CENTRAL, and the International HTA Database) for studies published between January 1, 2014 and December 31, 2022. All ICIs approved up to December 31, 2022, in the USA, EU, China, and Japan were included. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards published in 2013 (CHEERS 2013), which is the most widely recognised and implemented reporting guideline for HEE studies. Subgroup analyses were also performed based on the risk of sponsorship bias or citation of CHEERS 2013.</p><p><strong>Results: </strong>A total of 5368 records were identified, 252 of which were included after full-text review. The study design, setting, and ICIs most frequently observed were cost-effectiveness and cost-utility analyses (63.5%), the USA (46.0%), and pembrolizumab (38.1%), respectively. Of the 24 items of CHEERS 2013, fully reported items were limited, particularly in the Methods section. Setting and location were not reported in 94.4% of the records. Subgroup analyses also revealed insufficient reporting of items in the Methods section, particularly \"Setting and location\".</p><p><strong>Conclusion: </strong>Health economic evaluation studies on ICIs between 2014 and 2022 had limited reporting across the 24 items of CHEERS 2013, regardless of sponsorship bias risk or citations. The items on setting and location in the Methods section were particularly underreported, emphasising the need for transparent reporting in HEE studies of ICIs.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fremanezumab for the Treatment of Migraine Complicated by Medication Overuse: A Systematic Review.","authors":"Ibrahim Hajjaj, Carlo Baraldi, Lanfranco Pellesi","doi":"10.1007/s40261-025-01433-y","DOIUrl":"https://doi.org/10.1007/s40261-025-01433-y","url":null,"abstract":"<p><strong>Background: </strong>Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, such as fremanezumab, are effective for migraine prevention. However, their effectiveness in treating migraine complicated by medication overuse, remains underexplored.</p><p><strong>Objective: </strong>This systematic review aims to evaluate the effectiveness of fremanezumab in adults with migraine complicated by medication overuse.</p><p><strong>Methods: </strong>We systematically searched PubMed and Embase (Ovid) databases for studies on fremanezumab, selecting primary studies that included adults with migraine complicated by medication overuse and reported at least one efficacy outcome. The search was performed in January 2024 and then updated in June 2024. Risk of bias for randomized controlled trials was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, while real-world studies were evaluated using both the ROBINS-I and ROB-ME tools. Data extraction and analysis followed established guidelines.</p><p><strong>Results: </strong>Our search identified 176 records, of which 2 clinical trials and 7 real-world studies were included. Included studies recruited a total of 1422 adults with migraine complicated by medication overuse. In post hoc analyses from clinical trials, fremanezumab significantly reduced monthly migraine days, days with acute headache medication use, and Headache Impact Test (HIT-6) scores compared to placebo during a 12-week period. The real-world studies reported a reduction in monthly headache days at 6 months, and a high reversion rate from medication overuse headache (MOH) after one year of treatment.</p><p><strong>Conclusion: </strong>Both post hoc analyses from clinical trials and real-world studies support fremanezumab benefits in reducing migraine frequency, medication use, and headache-related disability in adults with migraine complicated by medication overuse. Given the limited quality of data, further real-world research with standardized reporting criteria is needed to substantiate long-term benefits and establish optimal treatment protocols.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Food on the Pharmacokinetic Characteristics of a Single Oral Dose of D-1553, a Selective Inhibitor of KRAS^G12C, in Healthy Chinese Subjects.","authors":"Yue Liu, Xin Gao, Yang Li, Xuemei He, Zhe Shi, Ling Zhang, Yaolin Wang, Aixin Shi","doi":"10.1007/s40261-025-01430-1","DOIUrl":"https://doi.org/10.1007/s40261-025-01430-1","url":null,"abstract":"<p><strong>Background and objective: </strong>D-1553 (garsorasib) is a novel and selective oral KRAS^G12C inhibitor. This study aims to evaluate the effect of food on the single-dose pharmacokinetics (PK) of D-1553 tablet in healthy Chinese subjects. Also the safety and tolerability of single-dose D-1553 in subjects are also evaluated.</p><p><strong>Methods: </strong>A randomized, open-label, single-dose, two-intervention (fed vs fasting), two-period, two-sequence crossover study was performed on 14 healthy Chinese subjects. Plasma concentrations of D-1553 were determined by the liquid chromatography-tandem mass spectrometry method. Safety evaluations were carried out during the study period. The main PK parameters of the two formulations of D-1553 were calculated by non-compartmental analysis using Phoenix WinNonlin (Version 8.3) software.</p><p><strong>Results: </strong>The geometric mean ratios (90% confidence interval [CI]) of AUC_0-t and AUC_0-∞ in the high-fat meal condition versus the fasting condition were 86.19% (78.30%, 94.87%) and 83.30% (75.77%, 91.58%), respectively. The geometric mean ratio (90% CI) of C_max values in high-fat meal condition to that observed in fasting condition were 109.74% (100.22%,120.15%). The p value of T_max was 0.1484 (fed vs fasting). Two subjects (14.3%) reported 4 treatment-emergent adverse events (TEAEs) in the fasting condition, and no subjects reported TEAEs in the fed condition. All adverse reactions were mild and had recovered by the end of the study.</p><p><strong>Conclusion: </strong>The study indicated that a high-calorie and high-fat meal has no clinically relevant impact on the PK and bioavailability of D-1553 in healthy Chinese subjects. D-1553 was generally safe and well-tolerated under both fasting and fed conditions. The findings suggest that D-1553 could be administered orally with or without food.</p><p><strong>Clinical trials: </strong>ClinicalTrials.gov Identifer CTR20212761; registered on 4 Nov 2021.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Pharmacodynamics, and Safety Evaluation of the Novel HIF-PH Inhibitor Enarodustat: An Open-Label Phase I Study in Healthy Chinese Participants.","authors":"Cheng Cui, Xiaoye Niu, Haiyan Li, Ruijie Zhang, Lei Geng, Wei Lin, Zichen Liu, Xiaohong Wang, Dongyang Liu","doi":"10.1007/s40261-025-01428-9","DOIUrl":"https://doi.org/10.1007/s40261-025-01428-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>Enarodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor. We evaluated the pharmacokinetics, pharmacodynamics, and safety profile of domestic enarodustat (SAL-0951) and analyzed the influence of ethnic factors.</p><p><strong>Methods: </strong>In this phase I study, healthy Chinese participants received single and multiple oral doses (1, 5, and 15 mg) of SAL-0951 while in a fasted state. We monitored the pharmacokinetics, pharmacodynamics, and safety characteristics and analyzed the impact of ethnicity on pharmacokinetic characteristics.</p><p><strong>Results: </strong>In total, 33 healthy Chinese participants were enrolled; the mean age was 31.2 ± a standard deviation of 5.5 years. After single doses of 1, 5, and 15 mg were administered under fasted conditions, SAL-0951 was rapidly absorbed. Mean maximum plasma concentration and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration increased dose proportionately from 0.14 to 2.54 μg/mL and from 0.63 to 9.50 h × μg/mL, respectively. The elimination half-life was 6.13, 6.32, and 6.74 h, respectively, in these three groups, and the mean value of apparent clearance ranged from 1.64 to 1.89 L/h. SAL-0951 was excreted mostly as the parent compound. It reached a stable concentration after 5 days of multiple-dose administration. We observed no drug accumulation or time-dependent pharmacokinetic characteristics and no significant difference in pharmacokinetic characteristics between Chinese and Japanese participants.</p><p><strong>Conclusion: </strong>SAL-0951 was safe and well tolerated in healthy Chinese participants and had a linear pharmacokinetic profile. We found no ethnic differences in the pharmacokinetic characteristics of the drug between Chinese and Japanese populations.</p><p><strong>Clinical trial registration: </strong>Registered at Chinadrugtrials.org.cn, registration number CTR2020245.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of Acute Kidney Injury After the Initiation of Vitamin D Receptor Activators: A Multicenter Retrospective Observational Study.","authors":"Masanori Nakanishi, Tomohiro Mizuno, Shinya Sakai, Daiki Hira, Takenao Koseki, Takeshi Matsubara, Hideki Yokoi, Motoko Yanagita, Tomohiro Terada, Shigeki Yamada, Naotake Tsuboi","doi":"10.1007/s40261-025-01429-8","DOIUrl":"https://doi.org/10.1007/s40261-025-01429-8","url":null,"abstract":"<p><strong>Background and objectives: </strong>Vitamin D receptor activators (VDRAs) are widely used in patients with osteoporosis; however, the frequency of acute kidney injury (AKI) due to VDRAs is unclear. This study aimed to investigate whether the incidence of AKI after VDRA initiation differed among patients with different renal functions.</p><p><strong>Methods: </strong>The medical records of Japanese patients who were newly prescribed with VDRAs for osteoporosis at the Fujita Health University Hospital or Kyoto University Hospital between April 2012 and March 2022 were retrospectively reviewed in this study. The RIFLE (Risk, Injury, Failure, Loss of function, End-stage kidney disease) criteria were used to assess the incidence of AKI within 7 days after initiation of VDRA therapy. Additionally, the AKI algorithm was used to assess the incidence of AKI from 8 to 365 days after initiation of VDRA therapy.</p><p><strong>Results: </strong>The incidence of AKI, as defined by the RIFLE criteria, was significantly higher in patients with normal renal function or end-stage renal failure than in those with mild renal decline (p < 0.05); the incidence of AKI, defined using the AKI algorithm, showed a similar trend. We found that the lack of serum calcium level monitoring before the initiation of VDRAs might be a risk factor for AKI defined by the RIFLE criteria (odds ratio = 2.004, p = 0.096).</p><p><strong>Conclusions: </strong>The incidence of AKI after the initiation of VDRA therapy was high, even if renal function was normal. Thus, our results suggest that monitoring serum calcium levels before the initiation of VDRA therapy is necessary, regardless of renal function.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guanfacine Use in the ICU for Management of Sedation Weaning.","authors":"Young R Lee, Alayna Garza, Laureen Kiama","doi":"10.1007/s40261-025-01434-x","DOIUrl":"https://doi.org/10.1007/s40261-025-01434-x","url":null,"abstract":"<p><p>Recent evidence highlights the increasing utilization of guanfacine in the intensive care unit. While dexmedetomidine is a widely used sedative and anti-anxiety agent in the intensive care unit, prolonged use can lead to withdrawal effects when attempting to reduce the dosage. This has generated interest in using guanfacine to manage agitation in patients being weaned off dexmedetomidine. Clonidine has been used for dexmedetomidine weaning, but its use has been associated with adverse cardiovascular events. Some observational studies and case reports have explored the use of guanfacine and have shown its benefits and tolerability for patients taking dexmedetomidine experiencing adverse effects. Guanfacine is increasingly being used in the intensive care unit instead of clonidine and is commonly prescribed for the management of withdrawal effects. While there are limited data from observational studies, it holds promise for future clinical research and broader adoption of guanfacine in the intensive care unit.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Comparison of Pharmacokinetics of Long-Acting Local Analgesics: CPL-01, a Novel Extended-Release Ropivacaine, Demonstrates Consistent and Predictable Exposure Compared with Liposomal Bupivacaine.","authors":"Stevie Pope, Christopher Crean, Sarah Thrasher, Hanghang Xu, P J Chen, Lee Chen, DeeDee Hu, Erol Onel","doi":"10.1007/s40261-025-01431-0","DOIUrl":"https://doi.org/10.1007/s40261-025-01431-0","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tebentafusp Versus Nivolumab Plus Ipilimumab for Metastatic Uveal Melanoma: An E-Value Sensitivity Analysis Assessing Effect of Unmeasured Confounders on Observational Associations.","authors":"Na Zhang, Yu-Wei Qiao, Dan Su, Guo Yu, Guo-Fu Li","doi":"10.1007/s40261-025-01422-1","DOIUrl":"10.1007/s40261-025-01422-1","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"165-168"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}