Clinical Drug Investigation最新文献

{"title":"The Effect of Multiple Oral Doses of a Glycine Transporter 1 Inhibitor, Iclepertin (BI 425809), on the Steady-state Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinylestradiol and Levonorgestrel: a Phase I Clinical Trial in Healthy Females.","authors":"Shilpa Madari, Yesilda Balavarca, Yury Shatillo, Corey Reuteman-Fowler, Michael Desch","doi":"10.1007/s40261-025-01472-5","DOIUrl":"10.1007/s40261-025-01472-5","url":null,"abstract":"<p><strong>Background: </strong>Iclepertin is a selective inhibitor of glycine transporter 1 recently investigated as a novel treatment for cognitive impairment associated with schizophrenia. Iclepertin is a potential mild inducer of liver cytochrome P450 3A4, which metabolises ethinylestradiol and levonorgestrel, which are used in combined oral contraceptives (OCs).</p><p><strong>Objectives: </strong>This trial investigated the potential drug interaction effect of steady-state iclepertin on the steady-state pharmacokinetics of combined OCs.</p><p><strong>Methods: </strong>This phase I, non-randomised, open-label, two-period, fixed-sequence trial was conducted in healthy pre-menopausal female volunteers aged 18-35 years. In period 1, participants received a combined OC (ethinylestradiol 30 µg/levonorgestrel 150 µg once daily; reference treatment). In period 2, participants received a combined OC and iclepertin 10 mg once daily (test treatment). Primary pharmacokinetic endpoints of ethinylestradiol or levonorgestrel in plasma at steady state over a uniform dosing interval τ were area under the concentration-time curve (AUC_τ,ss) and maximum and minimum measured concentration (C_max,ss and C_min,ss); drug interaction potential was estimated by geometric mean ratios (test treatment/reference treatment) with two-sided 90% confidence intervals (CIs) using analysis of variance. Safety assessments included monitoring adverse events (AEs).</p><p><strong>Results: </strong>In total, 19 participants entered the trial; 17 were treated (periods 1 and 2). Steady-state pharmacokinetics of ethinylestradiol and levonorgestrel were similar with and without iclepertin; geometric mean ratios for AUC_τ,ss, C_max,ss, and C_min,ss were slightly above 100%, and 90% CIs were within standard bioequivalence boundaries (80-125%). The number of on-treatment AEs was similar in period 1 (n = 13) and period 2 (n = 15); AEs were of mild-to-moderate severity.</p><p><strong>Conclusion: </strong>Iclepertin 10 mg had no meaningful effect on the pharmacokinetics of ethinylestradiol and levonorgestrel, suggesting that these drugs can be administered concomitantly.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT05613777; registered on 18 October 2023).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"767-779"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991673","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":"Off-Label Prescription of Benzodiazepines: A Retrospective Cohort Study of Prescribing Prevalence in Primary Care.","authors":"Kevin Trimm, Maria-Teresa Moraga, Bärbel Knäuper, Elham Rahme, Emily Gibson McDonald, Robyn Tamblyn","doi":"10.1007/s40261-025-01476-1","DOIUrl":"10.1007/s40261-025-01476-1","url":null,"abstract":"<p><strong>Background and objectives: </strong>Benzodiazepines are commonly prescribed medications approved for and used in the treatment of anxiolytic and sleep disorders, as well as for seizures, and alcohol withdrawal. However, benzodiazepines are also controlled substances because of their potential for abuse and personal harm, which are especially prevalent among older people. It is therefore important to understand how benzodiazepines are being prescribed, and the prevalence of off-label benzodiazepine prescribing, of which very little is known because of challenges in documenting treatment indication. The aim of this study was to detail the prevalence of benzodiazepine off-label prescribing.</p><p><strong>Methods: </strong>Data from the MOXXI (Medical Office of the XXIst century) electronic health record system in Quebec Canada were used, where specifying the treatment indication for each prescription is required, to estimate the prevalence of off-label prescribing and indications for off-label use of benzodiazepines. Each drug indication was retrospectively classified as either on-label or off-label according to the Health Canada drug database. Off-label prescriptions were further classified as having class congruence supporting their prescription if another benzodiazepine had been approved for the indication by Health Canada.</p><p><strong>Results: </strong>There were 20,125 (17.0%) adult patients prescribed benzodiazepines out of the 118,223 patients enrolled in the MOXXI system. The patients were predominantly female (65.6%) and tended to be older with an average age of 60.14 years at the time of the first benzodiazepine prescription. A total of 101,583 unique prescriptions were written for 14 different benzodiazepines. An approximately equal number of benzodiazepines were prescribed on- and off-label (49.3% on-label, 49.2% off-label). Most off-label prescription indications were classified as having class congruence (95.2%).</p><p><strong>Conclusions: </strong>Benzodiazepines were frequently prescribed in the province of Quebec and were prescribed off-label approximately half of the time. When prescribed off-label, we found that most of these prescriptions were for indications that were approved for other benzodiazepines. The most common indication for off-label benzodiazepine prescriptions with class congruence was insomnia.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"793-801"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999851","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":"Radioligand Therapies (RLTs) and Healthcare System Readiness: From the Experience in GEP-NET, a Retrospective Analysis on DRG and Mobility to Improve the Accessibility to the Future RLT in Italy.","authors":"Paolo Sciattella, Matteo Scortichini, Orazio Caffo, Marco Maccauro, Alfredo Muni, Francesco Panzuto","doi":"10.1007/s40261-025-01471-6","DOIUrl":"10.1007/s40261-025-01471-6","url":null,"abstract":"<p><strong>Background and objectives: </strong>Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare diverse group of malignancies, which range from well-differentiated indolent tumors to high-grade aggressive forms. Based on the World Health Organization classification, GEP-NETs are divided into well-differentiated neuroendocrine tumors and poorly differentiated carcinomas. While localized GEP-NETs are primarily treated surgically, non-resectable GEP-NETs have evolved toward targeted therapies, including radioligand therapy. This study describes inpatient resource utilization and inter-regional healthcare mobility for patients with GEP-NETs in Italy, focusing on radioligand therapy.</p><p><strong>Methods: </strong>We retrieved Italian Hospital Discharge Records (SDO) from 2018 to 2021. Given the absence of specific International Classification of Diseases, Ninth Revision, Clinical Modification codes for GEP-NETs, all potentially related diagnoses were included. Radioligand therapy-related hospitalizations were identified using Diagnosis-Related Group code 409 for radiotherapy, focusing on discharge disciplines of nuclear medicine, radiotherapy, or radiation oncology. We analyzed hospitalization rates by region and regimen and assessed inter-regional mobility using the Attraction and Escape Mobility Indexes.</p><p><strong>Results: </strong>Over the study period, 4837 radioligand therapy-related GEP-NET hospitalizations were recorded, with 2942 involving the targeted disciplines. Hospitalizations increased by 48.4%, mainly owing to growth in short-stay (0-1 day) discharges (from 37 in 2018 to 228 in 2021), while longer stays (≥ 2 days) rose from 552 to 644. Day hospital accounted for only 0.2% of cases. Regional disparities were prominent, with Emilia-Romagna, Lombardia, and Sicilia managing 88.9% of cases; ten regions recorded no hospitalizations, reflecting a high mobility index (45.8%) and significant inter-regional patient mobility.</p><p><strong>Conclusions: </strong>The study underscores the need for regulatory adjustments, resource allocation improvements, and healthcare system adaptations to effectively support innovative therapies for GEP-NETs. Addressing these needs is essential to optimize patient outcomes and address regional disparities in Italy's healthcare system.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"815-824"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Safety of Very-Low-Dose Rosuvastatin-Ezetimibe Therapy in Korean Patients with Dyslipidaemia: A Multicentre Prospective Observational Study.","authors":"Ji Woong Roh, Moon-Hwa Park, Ji-Won Son, SungA Bae","doi":"10.1007/s40261-025-01482-3","DOIUrl":"10.1007/s40261-025-01482-3","url":null,"abstract":"<p><strong>Background and objectives: </strong>Dyslipidaemia is a key modifiable risk factor for atherosclerotic cardiovascular disease. However, achieving recommended low-density lipoprotein cholesterol (LDL-C) target levels is challenging owing to dose-dependent adverse effects and limited tolerability of high-dose statins. This study evaluated the real-world efficacy and safety of combining very-low-dose rosuvastatin (2.5 mg) with ezetimibe (10 mg) in adult patients with dyslipidaemia across different cardiovascular risk strata.</p><p><strong>Methods: </strong>This multicentre prospective study in South Korea enrolled 2,388 patients. Participants were stratified into low-, moderate-, or high-risk groups on the basis of the 2019 European Society of Cardiology and European Atherosclerosis Society guidelines. Lipid profiles and safety outcomes were assessed at baseline and after 12 weeks. The primary and secondary outcomes were LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) target level achievements, respectively, and adverse events were monitored.</p><p><strong>Results: </strong>After 12 weeks, LDL-C target levels were achieved by 82.6% of low-risk (< 116 mg/dL), 73.9% of moderate-risk (< 100 mg/dL), and 50.4% of high-risk (< 70 mg/dL) patients. Non-HDL-C target level achievement followed a similar trend. Combination therapy with ezetimibe and low-dose statin resulted in significant LDL-C reductions, compared with statins alone. Adverse events were infrequent (0.6%), and only 0.2% of patients discontinued treatment owing to medication-related concerns.</p><p><strong>Conclusions: </strong>Very-low-dose rosuvastatin-ezetimibe combination therapy significantly lowered LDL-C levels and improved lipid profiles across various risk groups, demonstrating a favourable safety profile. These findings support its use as an effective, well-tolerated option for managing dyslipidaemia. Longer-term studies are warranted to evaluate sustained lipid control and cardiovascular outcomes.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"803-813"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069219","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":"Emerging Trends and Future Directions in the Development of Anti-hepatitis B Therapies: A Horizon Scanning Review.","authors":"Kaijie Yao, Hao Feng, Ying Chen, Yun Bao, Mengxia Yan, Wen Li, Bin Wu","doi":"10.1007/s40261-025-01477-0","DOIUrl":"10.1007/s40261-025-01477-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic hepatitis B virus infection remains a Major global public health challenge, affecting over 254 million individuals and causing substantial mortality owing to the limited curative potential of current therapies. This horizon scanning review aims to comprehensively analyze emerging trends and future directions in novel anti-hepatitis B virus therapeutic development, evaluating their progress and potential to achieve functional or complete cures.</p><p><strong>Methods: </strong>We conducted a systematic horizon scanning review from January 2020 to June 2025, searching databases (PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure [CNKI], and WanFang), clinical trial registries (ClinicalTrials.gov, EU Clinical Trials Register, World Health Organization International Clinical Trials Registry, Chinese Clinical Trial Registry, and chinadrugtrials.org), hepatology conference abstracts (American Association for the Study of Liver Diseases, European Association for the Study of the Liver), and pharmaceutical company websites. Inclusion criteria focused on studies detailing novel anti-hepatitis B virus treatments, with data extracted on category, target, clinical phase, and discontinuation reasons.</p><p><strong>Results: </strong>Our analysis identified 161 unique anti-hepatitis B virus treatments: 75 in clinical trials, 34 in preclinical development, and 52 discontinued post-clinical trials because of safety or insufficient efficacy. The pipeline reveals a diversification of targets, with capsid assembly modulators, therapeutic vaccines, and monoclonal antibodies being most prevalent. Three therapies representing novel mechanisms have reached phase III-bepirovirsen (an antisense oligonucleotide), canocapavir (a capsid assembly modulator), and εPA-44 (a therapeutic vaccine), illustrating diversification of late-stage pipelines; however, 6-month off-treatment endpoints should be interpreted cautiously across modalities until durability is established.</p><p><strong>Conclusions: </strong>The robust and diverse pipeline of novel anti-hepatitis B virus treatments offers promise for improving functional cure rates, but definitive conclusions await longer off-treatment follow-up and durability data. Continued research, rational combination strategies, and global collaboration are crucial to overcome challenges and ensure equitable access to these transformative therapies worldwide.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"681-700"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074664","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":"Low-Dose Propranolol versus Amitriptyline for Episodic Migraine Prophylaxis: A Randomized Controlled Trial Assessing Efficacy, Safety, and Cost-Effectiveness.","authors":"Vandana Roy, Nasra Banu, Girish Gulab Meshram, Debashish Chowdhury","doi":"10.1007/s40261-025-01481-4","DOIUrl":"10.1007/s40261-025-01481-4","url":null,"abstract":"<p><strong>Background and objectives: </strong>Direct head-to-head evidence of propranolol and amitriptyline for migraine prophylaxis is limited. This clinical trial compared the efficacy, safety, and cost-effectiveness of low-dose propranolol versus amitriptyline for episodic migraine prophylaxis over a 3-month period.</p><p><strong>Methods: </strong>This randomized, controlled, open-label, prospective, parallel, single-center trial was conducted at a tertiary care hospital in India. A total of 60 prophylaxis-naïve patients with episodic migraine were randomized 1:1 to receive either low-dose propranolol (80 mg/day) or amitriptyline (10 mg/day). The primary outcome was the improvement in the monthly headache frequency at 3 months from baseline, while the secondary outcomes included improvements from baseline in the proportions of patients achieving a ≥ 50% reduction in monthly headache days, headache severity, headache-induced disability, monthly rescue medication intake, quality of life, and cost-effectiveness (measured by the average cost-effectiveness ratio [ACER] and incremental cost-effectiveness ratio [ICER]).</p><p><strong>Results: </strong>At 3 months, propranolol showed a significantly greater reduction in monthly headache frequency compared with amitriptyline (- 3.67 ± 1.47 versus -  2.87 ± 1.36 days, P = 0.03). More patients in the propranolol group (60%) achieved a ≥ 50% reduction in monthly headache days compared with the amitriptyline group (43.33%) (P = 0.02). Propranolol also showed a greater reduction in monthly rescue medication intake (P = 0.01), but differences in headache severity, headache-induced disability, and quality of life were not significant. Both groups experienced mild adverse drug reactions. Cost-effectiveness analysis revealed propranolol had a higher ACER (US $5.44) and ICER (US $0.40/1% reduction) than amitriptyline.</p><p><strong>Conclusions: </strong>In our trial, low-dose propranolol demonstrated superior efficacy to amitriptyline in episodic migraine prophylaxis. Both drugs were well tolerated. Our study suggests that amitriptyline was more cost-effective than propranolol.</p><p><strong>Trial registration number: </strong>Clinical Trial Registry-India (Date: 27 October 2020; registration no.: CTRI/2020/01/022972).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"781-791"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032761","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":"A Retrospective Analysis of the Clinical and Economic Burden of Mitral Regurgitation in Italy Using Real-World Data.","authors":"Paolo Sciattella, Belén Martí-Sánchez, Matteo Vernia, Stefano Giardina, Federico De Marco","doi":"10.1007/s40261-025-01459-2","DOIUrl":"https://doi.org/10.1007/s40261-025-01459-2","url":null,"abstract":"<p><strong>Introduction: </strong>Mitral regurgitation (MR) is the second most common valve disease in Europe with an increasing prevalence, causing a significant healthcare burden and impacting quality of life. Despite its clinical importance, real-world data on MR burden are limited.</p><p><strong>Objectives: </strong>This study aimed to estimate MR prevalence, describe patient profiles, and assess healthcare resource utilization and related costs, stratified by degenerative (DMR) and functional (FMR) aetiologies, using real-world data from Italy.</p><p><strong>Methods: </strong>A retrospective study using Italy's Hospital Discharge Records was conducted including patients discharged in 2018 with a diagnosis of MR. The cohort was stratified into degenerative (DMR) and functional MR (FMR) based on comorbidities and clinical criteria. Patients were followed for 12 months to assess interventions received, including surgical (SMVr) and transcatheter mitral valve repair (TMVr), as well as length of stay, in-hospital mortality, and associated costs.</p><p><strong>Results: </strong>In 2018, 5816 patients who met the eligibility criteria were hospitalised with MR (83.6% DMR, 16.4% FMR). Among DMR patients, 44.2% underwent isolated valve repair (89.7% SMVr, 10.3% TMVr), while 29.1% of FMR patients received repair (59.6% SMVr, 40.4% TMVr). TMVr patients were older (DMR: 41.6%, FMR: 42.9% aged ≥75 years) and had more comorbidities. Untreated patients had higher 1-year in-hospital mortality (DMR: 4.7%, FMR: 8.5%) compared to treated groups and the highest reintervention rate at 1 year (DMR: 19.9%, FMR: 13.3%). Re-intervention rates were lower in DMR (SMVr: 0.4%, TMVr: 0%) versus FMR (SMVr: 0.6%, TMVr: 0.9%). The cost differences between interventions were negligible, primarily reflecting the different DRG tariffs applied for each intervention type.</p><p><strong>Conclusions: </strong>Untreated MR is associated with worse clinical outcomes and higher long-term resource use. These findings support early intervention strategies and highlight the need to improve access to care, especially for high-risk populations. Further studies are warranted to explore outpatient care and address treatment disparities.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184650","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":"CT-P47/Tocilizumab-anoh: A Tocilizumab Biosimilar.","authors":"Aisling McGuigan","doi":"10.1007/s40261-025-01483-2","DOIUrl":"https://doi.org/10.1007/s40261-025-01483-2","url":null,"abstract":"<p><p>CT-P47/tocilizumab-anoh (AVTOZMA^®) is a biosimilar of reference tocilizumab, an IL-6R inhibitor. CT-P47 is approved for treating rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, Coronavirus disease 2019 and cytokine release syndrome in the USA and the EU. CT-P47 has similar physicochemical properties to those of reference tocilizumab, with demonstrated pharmacokinetic comparability in patients with moderate to severe rheumatoid arthritis. In this patient population, CT-P47 demonstrated clinical efficacy equivalent to reference tocilizumab and was generally well tolerated. The overall safety and immunogenicity profiles of CT-P47 were similar to those of reference tocilizumab, and switching from reference tocilizumab to CT-P47 did not affect safety or efficacy. The role of reference tocilizumab in the management of inflammatory diseases is well established and CT-P47 provides an effective biosimilar alternative for patients requiring tocilizumab therapy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191449","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, Safety, and Tolerability of Efbemalenograstim Alfa (F-627), a Novel Long-Acting rhG-CSF, in Healthy Chinese Participants: An Open-Label, Single-Center Phase I Study.","authors":"Zhihai Cao, Yao Li, Denny Hou, Shufang Wang, Wei Yao, Gaochong Zhang, Jianmin Chen, Zhengwei Tang, Linda Song, Xingna Zhao, Xiaoxiang Chu, Xiaoyan Wang, Renshu Li, Wei Hu","doi":"10.1007/s40261-025-01488-x","DOIUrl":"https://doi.org/10.1007/s40261-025-01488-x","url":null,"abstract":"<p><strong>Background and objectives: </strong>In clinical practice, granulocyte colony-stimulating factor (G-CSF) is often used to lower infection risk and avoid poor outcomes from chemotherapy dose reduction or delay. Efbemalenograstim alfa (also known as F-627) is a non-pegylated but long-acting (once-per-cycle) recombinant human granulocyte colony-stimulating factor (rhG-CSF) compared with pegfilgrastim. This study was designed to obtain pharmacokinetic (PK)/pharmacodynamic (PD), safety, and tolerability data for F-627 in healthy Chinese participants.</p><p><strong>Methods: </strong>This was a single-center, open-label phase I clinical study involving 24 healthy Chinese volunteers (sex ratio = 1:1). All the participants were administered a single subcutaneous injection of 20 mg F-627 into the abdomen.</p><p><strong>Results: </strong>In this study, 15 (62.5%) participants reported 28 treatment-related adverse events. PK/PD data showed that after a single 20 mg subcutaneous (SC) F-627 abdominal injection in healthy Chinese participants, serum concentrations peaked at 36 h post dose, while the absolute neutrophil count (ANC) peaked at 96 h. After peaking, F-627 serum levels decreased rapidly to low concentrations by 120 h, while ANC declined gradually to near baseline by day 15. Similar trends in serum concentration and ANC kinetics were seen between sex.</p><p><strong>Conclusions: </strong>This phase I study showed that 20 mg F-627 was well tolerated and exhibited a favorable safety profile in a healthy Chinese population. The PK and PD data correlated well and were consistent across sex.</p><p><strong>Trial registration: </strong>This trial was registered at the Chinese Clinical Trial Registry (chictr.org.cn) on 10 September 2024 (registration ID: ChiCTR2400089548).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184668","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":"Resmetirom: The First FDA-Approved Drug for Metabolic Dysfunction-Associated Steatohepatitis (MASH) with a Perspective on Precision Medicine.","authors":"Fengshuo Zhang, Yicong Meng, Bohan Zhao, Ziang Li, Mengran Han, Ming Li, Yun Zhou","doi":"10.1007/s40261-025-01484-1","DOIUrl":"https://doi.org/10.1007/s40261-025-01484-1","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD) involving hepatocyte destruction, inflammation, and typically pericellular fibrosis, potentially progressing to cirrhosis. Resmetirom, a T3 analogue and an oral agonist of thyroid hormone receptor-β(THR-β), represents a significant advancement in targeted drug therapy for MASH as the first US Food and Drug Administration (FDA)-approved treatment. Clinical trials have shown that resmetirom effectively improves MASH markers, reduces liver fat content, and exhibits high selectivity for THR-β, which is predominantly expressed in the liver. Despite promising research data, challenges remain in the treatment of MASH with resmetirom, including adverse reactions and limited efficacy in some patients. This article reviews the discovery, mechanisms, and clinical evaluation of resmetirom in detail, and discusses the challenges encountered in MASH precision therapy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124546","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}