Clinical Drug Investigation最新文献

{"title":"Willingness to Pay for Treatment Attributes in Diffuse Large B-Cell Lymphoma: A Discrete Choice Experiment in Japan.","authors":"Yasuyuki Arai, Timothy Bolt, Hikaru Onishi, Michael LoPresti, Victoria Arguissain, Jörg Mahlich","doi":"10.1007/s40261-026-01549-9","DOIUrl":"10.1007/s40261-026-01549-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>Treatment decision-making in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is increasingly complex, especially with the emergence of novel, high-cost therapies such as chimeric antigen receptor (CAR) T-cell therapy. Understanding how physicians weigh various clinical and nonclinical treatment attributes is essential for aligning healthcare decisions with both clinical value and economic sustainability. This study aims to quantify Japanese physicians' preferences in health outcomes and patient experience outcomes through eliciting trade-offs in a choice experiment for specific treatment characteristics in R/R DLBCL.</p><p><strong>Methods: </strong>We performed a discrete choice experiment (DCE) with Japanese hematologists and oncologists. Participants completed an online best-worst scaling three alternative discrete choice experiment featuring a series of hypothetical treatment outcomes for DLBCL. The DCE included two patient vignettes: patient Q, a 70-year-old male with two prior treatment lines and Eastern Cooperative Oncology Group (ECOG) performance status 1; and patient R, a 58-year-old female with three prior treatment lines and ECOG performance status 2. Predefined attributes included: overall survival (OS) rates at 12 and 24 months, change in ECOG status at 6 months, CAR-T related side effects (risk of severe cytokine release syndrome (CRS), and risk of severe neurological events), duration of hospitalization, time until treatment initiation, and total treatment cost. A conditional logit model was used to calculate odds ratios (OR) for each attribute's influence on selecting the preferred treatment recommendation. ORs were translated into willingness-to-pay (WTP) estimates for the health outcomes, changes in adverse event risks and waiting time/hospitalization duration.</p><p><strong>Results: </strong>A total of 231 Japanese hematologists and oncologists participated, each making six treatment decisions for two patient vignettes. Across both profiles, 12- and 24-month overall survival (OS), hospitalization duration, waiting time, and treatment cost significantly influenced preferences. For patient Q, reduced CRS risk was significant, while for patient R, ECOG improvement was influential. Willingness to pay (WTP) for a 1% increase in 24-month OS was approximately JPY 1.4 million (~USD 9520) for patient Q and JPY 1.8 million (~USD 12,240) for patient R; corresponding estimates for 12-month OS were slightly lower. A 1-week reduction in hospital stay was valued at JPY 1.1-1.9 million (USD 7480-12,920), and a 1-week reduction in waiting time at JPY 600,000-1.5 million (USD 4080-10,200). Overall, physicians prioritized long-term survival more strongly for the younger, more severe patient, whereas preferences were more balanced for the older patient. Clinical improvement (ECOG) weighed more heavily for the younger patient, while safety concerns were more salient in the older case.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"619-630"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653826","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":"Correction: A Single-Center, Randomized, Open-Label, Two-Formulation, Two-Sequence, Two-Period Crossover Study to Evaluate the Bioequivalence of Two Eltrombopag Olamine Tablets (25 mg) in Healthy Chinese Subjects in the Fed State.","authors":"Keyi Wu, Qing Ren, Yanli Wang, Yannan Zhou, Zhengzhi Liu, Yang Cheng, Qiaohuan Deng, Yingzi Cui, Haimiao Yang","doi":"10.1007/s40261-026-01542-2","DOIUrl":"10.1007/s40261-026-01542-2","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"681"},"PeriodicalIF":2.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764588","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":"Efficacy and Safety of Topical Anticholinergics in the Treatment of Primary Axillary Hyperhidrosis: A Systematic Review and Meta-analysis.","authors":"Jiah Kim, Nayoung Han, Hyunji Koo, Younghwa Kim, Eun Jung Hwang, Min-Soo Kim, Christine E Staatz, In-Hwan Baek","doi":"10.1007/s40261-026-01550-2","DOIUrl":"10.1007/s40261-026-01550-2","url":null,"abstract":"<p><strong>Background: </strong>Topical anticholinergic agents are non-invasive treatment options for primary axillary hyperhidrosis (PAH). Sofpironium bromide was recently approved by the US Food and Drug Administration (FDA). A comprehensive evaluation of the efficacy and safety of available topical anticholinergics may inform clinical practice.</p><p><strong>Objectives: </strong>To assess the efficacy and safety of topical anticholinergic therapies for PAH through systematic review and meta-analysis of randomized controlled trials (RCTs).</p><p><strong>Methods: </strong>Five databases were searched on September 9, 2024. Primary outcomes included a ≥2-point improvement in the Hyperhidrosis Disease Severity Scale (HDSS) and ≥50% reduction in gravimetric sweat production (GSP). Secondary outcomes included subjective symptom improvement and objective sweat reduction. Safety outcomes included treatment-emergent adverse events (TEAEs), anticholinergic-related adverse events, and local application site reactions. The review protocol was registered in PROSPERO (CRD42024583376).</p><p><strong>Results: </strong>Eight RCTs (n = 1921) that evaluated glycopyrronium, sofpironium bromide, and umeclidinium were included. Topical agents significantly outperformed placebos for HDSS ≥2-point improvement (risk ratio [RR]: 2.40; 95% confidence interval [CI]: 2.01-2.86) and GSP ≥50% reduction (RR: 1.43; 95% CI: 1.21-1.70). Sofpironium was the most effective HDSS treatment, whereas glycopyrronium showed highest efficacy against GSP. Topical agents were associated with increased risk of TEAEs (RR: 1.43; 95% CI: 1.14-1.79), with sofpironium associated with highest risk of dry mouth and glycopyrronium with highest risks for mydriasis and constipation.</p><p><strong>Conclusions: </strong>Topical anticholinergic agents are effective for PAH treatment, with distinct efficacy and safety profiles. Although the available evidence is limited by the small number of trials, short follow-up durations, and heterogeneity in outcome reporting, these findings support the role of topical anticholinergic therapy as an effective non-invasive option for PAH.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"583-594"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698049","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":"Comparative Sensory Evaluation of Pediatric Liquid Omeprazole Formulations Available in the UK.","authors":"Sejal R Ranmal, Elisa Alessandrini, Catherine Tuleu","doi":"10.1007/s40261-026-01548-w","DOIUrl":"10.1007/s40261-026-01548-w","url":null,"abstract":"<p><strong>Background: </strong>Omeprazole is a widely prescribed proton pump inhibitor used to treat gastroesophageal reflux disease and other acid-related disorders in children. Despite its clinical importance, the availability of licensed liquid formulations varies worldwide, often resulting in the use of extemporaneously compounded preparations. These liquid products have varying sensory characteristics that can influence patient acceptability.</p><p><strong>Methods: </strong>A randomized, single-blind sensory evaluation study was conducted with a panel of 30 adult volunteers (aged 24 ± 2.6 years; 77% female) to assess the palatability of six omeprazole liquid formulations available in the UK. Participants rated taste, aftertaste, smell, and mouthfeel aversiveness using a visual analog scale, overall acceptability using a 5-point facial hedonic scale, and provided qualitative feedback.</p><p><strong>Results: </strong>The compounded 8.4% sodium bicarbonate suspension had a significantly more aversive taste (mean ± standard deviation: 74 ± 31; median [interquartile range]: 83 [63-100]) and aftertaste (55 ± 33; 61 [23-80]) compared with all licensed formulations (p < 0.001), with bitterness being a prominent attribute. The licensed menthol-flavored 10-mg/15-mL oral solution received the lowest taste aversiveness rating (17 ± 23; 6 [1-19]), and the highest overall acceptability. Other licensed formulations were generally rated as mild to moderately aversive, with some irritating or burning sensations also reported.</p><p><strong>Conclusions: </strong>A sensory analysis revealed clear differences between compounded and licensed omeprazole formulations, highlighting the importance of developing and prescribing palatable age-appropriate formulations for pediatric populations.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"669-680"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608328","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":"Clinical Benefit of Multiple Myeloma Drugs at Regulatory Approval in Brazil, Europe, and the USA: A Retrospective Cohort Study (2003-2024).","authors":"Marina Alacoque Rodrigues, Cristiane Aparecida Menezes de Pádua, Paula Lana de Miranda Drummond, Pedro Henrique Carvalho de Souza, Jéssica Soares Malta, Adriano Max Moreira Reis","doi":"10.1007/s40261-026-01552-0","DOIUrl":"10.1007/s40261-026-01552-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>The value of new therapies depends on the magnitude of their clinical benefit. In multiple myeloma (MM), numerous drugs have been approved in the past two decades, yet the extent of clinical benefit at authorization remains uncertain. This study evaluated MM drugs approved by the European Medicines Agency (EMA), the Food and Drug Administration (FDA), and the Brazilian Health Regulatory Agency (Anvisa).</p><p><strong>Methods: </strong>This retrospective cohort study assessed MM drugs approved between 2003 and 2024. Data were extracted from publicly available regulatory documents. Clinical benefits were assessed using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale for Haematological Malignancies (ESMO-MCBS:H v 1.1) based on pivotal trials. Descriptive statistics, Kaplan-Meier curves and log-rank tests were performed.</p><p><strong>Results: </strong>During the study period, the EMA approved 17 drugs for MM, with 11 (64.7%) supported by single-arm studies and 4 (23.5%) through accelerated assessment. The FDA also approved 17 drugs, with 12 (70.6%) based on single-arm studies, 11 (64.7%) through expedited pathways, and 8 (47.1%) designated as Breakthrough Therapies. Anvisa approved 12 drugs, with 7 (58.3%) under priority registration. According to the ESMO-MCBS:H v1.1 scoring, only 4 of 17 drugs (23.5%) demonstrated meaningful clinical benefit, defined as a grade ≥4 in the non-curative setting. Accelerated timelines in Brazil were significantly associated with biologicals, monoclonal antibodies, and Breakthrough Therapy status (all p < .05).</p><p><strong>Conclusion: </strong>Most MM therapies approved entered the market with limited evidence of meaningful clinical benefit. These findings support using the ESMO-MCBS:H to guide regulatory and reimbursement decisions in resource-constrained settings.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"641-653"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764579","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":"Budget Impact Analysis of Pulsed Field Versus Cryoballoon and Laser Procedures for Atrial Fibrillation in Italy.","authors":"Erika Fiumalbi, Ilaria Valentini, Marzia Giaccardi, Chiara Bartoli, Maria Lucia Narducci, Giovanni Arcuri, Carmen Furno","doi":"10.1007/s40261-026-01540-4","DOIUrl":"10.1007/s40261-026-01540-4","url":null,"abstract":"<p><strong>Background and objectives: </strong>Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with a higher prevalence due to the ageing of the population. Traditional ablation techniques, such as cryoballoon ablation (CB) and laser ablation (LA), are widely used but may be associated with longer procedure times and a risk of collateral tissue injury. Pulsed field ablation (PFA) is an emerging non-thermal technology that uses electroporation, with early evidence suggesting a favourable safety profile and improved procedural efficiency. This study assessed the budget impact of the introduction of PFA within the Italian National Health Service (NHS) compared with current CB and LA practice, estimating short-term differences in healthcare costs to support resource allocation decisions.</p><p><strong>Methods: </strong>A 5-year budget impact model compared two scenarios: current clinical practice (CB and LA) and a progressive uptake of PFA, increasing from 20% in 2025 to 67.2% in 2029. The analysis included direct medical costs: device acquisition, staff time, procedural resources, complications and repeat interventions. The population and treatment assumptions were based on national and regional data from Italy. The analysis was conducted from the perspective of the NHS. A deterministic sensitivity analysis was performed to assess the robustness of the results.</p><p><strong>Results: </strong>The introduction of PFA resulted in cumulative cost savings of €11.7 million over 5 years. In the current scenario, costs increased from €36.2 million to €38.1 million. In contrast, costs in the PFA scenario decreased from €35.8 million to €33.2 million. The main savings came from reduced staff and procedural costs (€7.6 million), fewer recurrences (€5.9 million) and lower costs related to complication (€1.5 million). Sensitivity analysis confirmed the robustness of the results, with device cost, CB pricing and procedure time identified as the most influential parameters.</p><p><strong>Conclusions: </strong>Our study suggests that the progressive integration of PFA into routine AF care within the Italian NHS could generate meaningful cost savings while maintaining clinical outcomes.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"655-667"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590379","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":"Pharmacokinetic Drug-Drug Interaction of Leritrelvir in Healthy Chinese Volunteers: A Single-Arm, Open-Label, Dual-Cohort Study.","authors":"Jiao Peng, Juan Chen, Xiao-Xiao Du, Hai-Jun Li, Ru-Zhai Qin, Si-Han Chen, Xian Liu, Qi Cheng, Xiao-Mei Li, Dong-Xiang Huang, Lian Duan, Ming-Yan Li, Wen-Zheng Wu, Li-Ka Ye, You-Yun Li, Zhi-Hong Xie, Ke Han","doi":"10.1007/s40261-026-01556-w","DOIUrl":"10.1007/s40261-026-01556-w","url":null,"abstract":"<p><strong>Background and objectives: </strong>Preclinical studies have shown that leritrelvir, an anti-coronavirus disease 2019 (COVID-19) drug, is a substrate of CYP3A and P-gp. It also inhibits CYP3A, CYP2C19, and OATP1B3. This study systematically evaluated leritrelvir's pharmacokinetic interactions with sensitive substrates, inhibitors, or inducers of the aforementioned metabolic pathways. The short-term safety of co-administration was also assessed.</p><p><strong>Methods: </strong>We conducted a phase Ⅰ, single-arm, open-label, dual-cohort clinical trial in healthy Chinese adults. Cohort 1 evaluated the effect of multiple doses of leritrelvir on the pharmacokinetics of midazolam, omeprazole, and rosuvastatin. Serial blood samples were collected for the determination of midazolam and omeprazole concentrations at pre-dose and post-dose on days 1-2 (midazolam and omeprazole alone) and days 10-11 (midazolam and omeprazole co-administered with leritrelvir). For rosuvastatin, blood samples were collected at pre-dose and post-dose on days 3-6 (rosuvastatin alone) and days 12-15 (rosuvastatin co-administered with leritrelvir). Cohort 2 assessed the effect of multiple dose administration of verapamil and rifampicin on the pharmacokinetics of leritrelvir. Serial blood samples were collected for the determination of leritrelvir concentrations at pre-dose and post-dose on days 1-4 (leritrelvir alone), days 9-12(leritrelvir co-administered with verapamil), and days 28-31(leritrelvir co-administered with rifampicin).</p><p><strong>Results: </strong>In cohort 1, leritrelvir minimally affected omeprazole and rosuvastatin exposure. The geometric mean ratios (GMRs) for their area under the plasma concentration-time curve from time zero to the lowest detectable plasma concentration (AUC_0-t) were 98.3% and 113.2%, respectively, versus administration alone. In contrast, leritrelvir increased midazolam AUC_0-t to 232.1% (GMR) versus administration alone. In cohort 2, verapamil increased leritrelvir AUC_0-t to 251.8% (GMR) versus administration alone. Rifampicin decreased leritrelvir AUC_0-t to 80.6% (GMR).</p><p><strong>Conclusions: </strong>The potential for drug-drug interactions between leritrelvir and CYP2C19 or OATP1B3 is low. The same applies to its interaction with a CYP3A inducer. However, as a moderate CYP3A inhibitor, leritrelvir requires caution when co-administered with CYP3A substrates, especially those with a narrow therapeutic index. Although moderate inhibitors of CYP3A and P-gp increased the leritrelvir exposure, this increase may not require dose adjustment on the basis of the phase I PK data of leritrelvir.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT06031454.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"609-618"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811778","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":"Cost Effectiveness of Osimertinib with Chemotherapy Compared to Osimertinib Monotherapy and First-Generation EGFR-TKIs in Advanced NSCLC in the USA.","authors":"Mohammad Alnuman, Kangho Suh","doi":"10.1007/s40261-026-01535-1","DOIUrl":"10.1007/s40261-026-01535-1","url":null,"abstract":"<p><strong>Background and objectives: </strong>In clinical trials, osimertinib combined with chemotherapy has demonstrated improved efficacy in patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer. However, the projected long-term outcomes and the associated cost effectiveness compared to osimertinib monotherapy and first-generation EGFR-tyrosine kinase inhibitors remain uncertain.</p><p><strong>Methods: </strong>A lifetime partitioned survival model was developed from the US healthcare sector perspective using clinical trial data from pivotal trials FLAURA and FLAURA2. Model inputs included drug costs, administration costs, and health utilities sourced from the published literature. Dynamic drug pricing and a 3% discount rate were incorporated. Outcomes included life-years, quality-adjusted life-years (QALYs), total costs, and incremental cost-effectiveness ratios. One-way and probabilistic sensitivity analyses were performed.</p><p><strong>Results: </strong>Combination therapy yielded 2.96 QALYs at a cost of $692,796. The resultant incremental cost-effectiveness ratio was $265,601/QALY versus osimertinib monotherapy and $467,747/QALY versus first-generation EGFR-tyrosine kinase inhibitors. Findings were consistent across sensitivity analyses.</p><p><strong>Conclusions: </strong>While clinically effective, based on commonly accepted cost-effectiveness thresholds in the USA, our study suggests that osimertinib plus chemotherapy was not cost effective compared to osimertinib alone or first-generation EGFR-tyrosine kinase inhibitors.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"541-549"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289159","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":"Determinants and Prognostic Impact of In-Hospital Sodium-Glucose Cotransporter-2 Inhibitor Initiation in Patients with Heart Failure.","authors":"Takuya Okamoto, Koichiro Matsumura, Shohei Hakozaki, Eijiro Yagi, Kazuyoshi Kakehi, Ayano Yoshida, Takayuki Kawamura, Kosuke Fujita, Masafumi Ueno, Kimiko Fujiwara, Manabu Takegami, Gaku Nakazawa","doi":"10.1007/s40261-026-01539-x","DOIUrl":"10.1007/s40261-026-01539-x","url":null,"abstract":"<p><strong>Background and objectives: </strong>Initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients hospitalised for heart failure (HF) is crucial for improving long-term outcomes. However, in real-world practice, a considerable proportion of patients are discharged without initiation. This study aimed to evaluate the initiation rate of SGLT2i, identify clinical factors associated with non-initiation, and examine the impact on long-term prognosis in patients hospitalised for HF.</p><p><strong>Methods: </strong>This single-centre, retrospective, observational analysis of a prospective registry included 781 consecutive patients who were hospitalised for HF between 2021 and 2024. The primary endpoint was the in-hospital initiation rate of SGLT2i. Secondary endpoints included clinical factors associated with non-initiation, assessed using multivariable logistic regression, and the incidence of the composite endpoint of all-cause mortality or HF rehospitalisation at 1 year according to SGLT2i prescription status at discharge, evaluated by log-rank test and Cox proportional hazards analysis.</p><p><strong>Results: </strong>A total of 467 patients (median age 81 [74-87] years, 50.3% male) were included in the final analysis. The initiation rate of SGLT2i during hospitalisation was 37.3% (174/467), and treatment discontinuation after initiation occurred in 8.6% (15/174). Multivariable analysis revealed that older age, non-diabetes, impaired renal function, higher left ventricular ejection fraction, malnutrition, impaired mobility, and cognitive dysfunction were independently associated with non-initiation. Among 346 patients with available follow-up data, the incidence of the composite endpoint at 1 year was significantly higher in the non-initiation group than in the initiation group (37.5% vs 21.3%, log-rank p = 0.001). In multivariable Cox analysis, not prescribed SGLT2i at discharge remained independently associated with worse long-term outcomes (hazard ratio 1.70, 95% confidence interval 1.07-2.69, p = 0.02).</p><p><strong>Conclusion: </strong>Both conventional clinical factors (e.g., diabetes, left ventricular ejection fraction) and aging-related factors (e.g., nutritional status, mobility, cognitive function) were independently associated with non-initiation of SGLT2i in hospitalised patients with HF. Importantly, non-initiation at discharge was significantly associated with worse long-term outcomes, underscoring the need to promote active initiation of SGLT2i in this population.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"489-499"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442928","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":"Effects of Ensitrelvir on the Pharmacokinetics of Combined Oral Contraceptives (Ethinyl Estradiol/Drospirenone) in Healthy Adult Women: A Phase 1 Fixed-Sequence, Multiple-Dose, Drug-Drug Interaction Study.","authors":"Ryosuke Shimizu, Risa Yokokawa Shibata, Ryuji Kubota, Sho Okuda, Takuhiro Sonoyama","doi":"10.1007/s40261-026-01541-3","DOIUrl":"10.1007/s40261-026-01541-3","url":null,"abstract":"<p><strong>Background and objective: </strong>Ensitrelvir has shown cytochrome P450 3A (CYP3A) inhibitory/induction potential in in vitro studies. This open-label, fixed-sequence Phase 1 study evaluated potential drug-drug interactions between ensitrelvir and a combined oral contraceptive (COC) containing ethinyl estradiol (EE) and drospirenone in healthy women of childbearing age.</p><p><strong>Methods: </strong>Healthy premenopausal women received EE/drospirenone (0.02 mg/3 mg) on days 1-24. Ensitrelvir was co-administered on day 20 (375 mg) and days 21-24 (125 mg/day). Blood samples were collected on days 19, 20, and 24 to assess plasma EE, drospirenone, and ensitrelvir concentrations. The primary endpoint was evaluation of the maximum plasma concentration, time to maximum plasma concentration, and area under the plasma concentration-time curve over the dosing interval τ (AUC_0-τ) assessed using noncompartmental methods. Treatment-emergent adverse events (TEAEs) were recorded for safety assessments.</p><p><strong>Results: </strong>The safety and pharmacokinetic parameter population comprised 24 and 23 participants, respectively. Compared with day 19, AUC_0-τ ratios on days 20 and 24 were 1.02- and 1.07-fold for EE and 1.10- and 1.80-fold for drospirenone, respectively. This result suggested the inhibitory potential for CYP3A to be likely weaker on the first day than on the last day. Ensitrelvir AUC_0-τ was higher on day 24 versus day 20 and comparable with that reported previously. Treatment-emergent adverse events occurred in 58.3% of participants, none of which were severe, serious, or led to treatment discontinuation.</p><p><strong>Conclusion: </strong>Ensitrelvir has no clinically meaningful effect on the pharmacokinetics of EE and drospirenone, and the combination was well tolerated. These findings support the co-administration of ensitrelvir with COCs in clinical practice.</p><p><strong>Trial registration: </strong>NCT06775730.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"561-570"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580472","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}