Clinical therapeutics最新文献

{"title":"Biomarkers: A Concept in Reach of Maturity.","authors":"Paul Beninger","doi":"10.1016/j.clinthera.2025.08.016","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.016","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRINSUPRI (brensocatib).","authors":"Paul Beninger","doi":"10.1016/j.clinthera.2025.08.011","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.011","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing the Time Interval Suppresses Adverse Effects After Concomitant Use of Nafamostat Mesylate and Levocarnitine in Dialysis Patients: Case Series.","authors":"Lili Jiang, Jiaoyan Chen, Jurong Yang, Yan Sun, Mingyue Hou, Yunyan Wang","doi":"10.1016/j.clinthera.2025.08.014","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.014","url":null,"abstract":"<p><strong>Purpose: </strong>This is a series of reports describing how increasing the time interval between the administration of nafamostat mesylate (NM) and levocarnitine can suppress adverse reactions in maintenance hemodialysis patients after medication.</p><p><strong>Methods: </strong>Clinical assessments and medical record collection were conducted by nephrologists and nurses, while laboratory tests were performed by specialist doctors.</p><p><strong>Findings: </strong>Increasing the time interval between NM and levocarnitine administration (15-25 minutes) reduced adverse drug reactions, including nausea and vomiting, in 4 patients.</p><p><strong>Implications: </strong>This may provide clinical doctors with new insights and research directions when using levocarnitine and NM for dialysis treatment.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Fimasartan, Atorvastatin, and Ezetimibe Combination Therapy in Patients With Hypertension and Dyslipidemia: A Randomized, Double-Blind, Multicenter, Therapeutic Confirmatory, Phase III Clinical Trial.","authors":"Soon Jun Hong, Ju Hyeon Kim, Kwang Soo Cha, Jin Bae Lee, Jae Youn Moon, Goo-Yeong Cho, Deok-Kyu Cho, Jong-Pil Park, Jeong-Eun Yi, Kye Hun Kim, Hyeonju Jeong, Moo-Yong Rhee, Jung-Hee Lee, Kye Tack Ahn, Young Won Yoon, Sang-Yeub Lee, Ki-Chul Sung, Tae-Joon Cha, Jinho Shin, Yoon Haeng Cho, Jang-Won Son, Jong-Hwa Ahn, Sang-Don Park, Woong Chol Kang, Joo-Yong Hahn, Jong-Won Ha","doi":"10.1016/j.clinthera.2025.08.012","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.012","url":null,"abstract":"<p><strong>Background: </strong>Essential hypertension and primary hypercholesterolemia are common and independent cardiovascular risk factors that frequently coexist and warrant integrated management. This study aimed to evaluate the efficacy and safety of triple combination therapy (FMS + ATO/EZE) with Fimasartan (FMS), atorvastatin (ATV), and ezetimibe (EZE) compared with atorvastatin/ezetimibe (ATO/EZE) dual therapy or Fimasartan (FMS) monotherapy in patients with hypertension and hypercholesterolemia.</p><p><strong>Methods: </strong>This multicenter, randomized clinical trial was conducted across 25 clinical trial institutions in the Republic of Korea. A total of 315 participants were screened, of whom 148 eligible participants were randomized to receive FMS + ATO/EZE (n = 49), ATO/EZE (n = 49), or FMS (n = 50). The primary efficacy endpoints were the change in mean sitting systolic blood pressure (msSBP) from baseline to week 8 in the FMS + ATO/EZE group compared with that in the ATO/EZE group and the percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 8 in the FMS + ATO/EZE group compared with that in the FMS group. Safety was assessed based on treatment-emergent adverse events (TEAEs).</p><p><strong>Results: </strong>In the full analysis set, the FMS + ATO/EZE group demonstrated superior reduction in msSBP compared to the ATO/EZE group (least squares [LS] mean difference: -7.26 ± 2.84 mm Hg; 95% confidence interval [CI]: -12.91, -1.61; P = 0.0124). Similarly, the percentage reduction in LDL-C was significantly greater in the FMS + ATO/EZE group than in the FMS group (LS mean difference: -58.02% ± 4.03%; 95% CI: -66.03, -50.02; P < 0.0001). The incidence of TEAEs was comparable across treatment groups: FMS + ATO/EZE (20.83%), ATO/EZE (22.45%), and FMS (16.00%) (P = 0.7030). Serious adverse events occurred in 1.36% of the total safety population, without significant difference between the groups (P = 0.5480).</p><p><strong>Conclusions: </strong>Triple combination therapy with FMS + ATO/EZE was superior to dual therapy or monotherapy in reducing both BP and LDL-C levels in patients with essential hypertension accompanied by primary hypercholesterolemia. The safety profile was comparable with that of the individual components, confirming the tolerability and safety of FMS + ATO/EZE therapy. However, the 8-week follow-up period and enrollment of an exclusively Korean cohort may limit the assessment of long-term effects and generalizability to other ethnic populations.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase III Randomized Controlled Trial Evaluating the Efficacy and Safety of Azilsartan Medoxomil and Amlodipine Combination Therapy in Patients With Mild-to-Moderate Essential Hypertension Inadequately Controlled on Monotherapy.","authors":"Dae-Hee Kim, Sang Hyun Lee, Kyung Ah Han, Moo Hyun Kim, Dong-Ju Choi, Marcin Grabowski, Pawel Miekus, Tzung-Dau Wang, Ching-Pei Chen, Sungha Park","doi":"10.1016/j.clinthera.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.003","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the antihypertensive efficacy and safety of azilsartan medoxomil (AZM) and amlodipine (AML) combination therapy in patients with mild-to-moderate hypertension inadequately controlled by AZM or AML monotherapy.</p><p><strong>Methods: </strong>In this multicenter, randomized, double-blind Phase III study (NCT05385770), patients with mild-to-moderate hypertension inadequately controlled with AZM 40/80 mg or AML 5/10 mg were randomized (1:1:1) to receive low-dose or high-dose AZM/AML combination therapy or continued monotherapy as control. Eligible patients completed a 4-week active run-in period before randomization. The primary endpoint was change from baseline in mean sitting systolic blood pressure (SBP) after 8 weeks of treatment.</p><p><strong>Findings: </strong>A total of 890 patients were randomized. AZM/AML combination therapy resulted in significantly greater reductions in mean sitting SBP compared with AZM or AML monotherapy across all dose groups. Least-squares mean reductions in mean sitting SBP at week 8 ranged from 5.2 to 9.0 mm Hg across all monotherapy nonresponder groups, with all comparisons showing statistical significance (P < 0.05). Reductions in mean sitting diastolic blood pressure also favored combination therapy. Safety profiles were comparable across all treatment arms, with most adverse events mild or moderate in severity. No additional safety concerns were identified compared with monotherapy.</p><p><strong>Implications: </strong>AZM/AML combination therapy was more effective than monotherapy in patients with mild-to-moderate hypertension inadequately controlled with either agent alone, even at maximum doses. Both low-dose and high-dose combinations were well tolerated. AZM/AML combination therapy may offer enhanced BP-lowering efficacy compared with other angiotensin II receptor blocker-based regimens.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Chilling of Data Sharing and Reuse: Lives at Greater Risk in the Current Era.","authors":"Joel Cutcher-Gershenfeld, Paul Beninger, Alan Blatecky, Pat Canavan, Jill Gemmill, Brooks Hanson, John C Klensin, Michael Maffie, Erezi Ogbo-Gebhardt, Rajesh Sampath, Namchul Shin, Susan Winter, Kimberly E Zarecor","doi":"10.1016/j.clinthera.2025.08.006","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.006","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Ursodeoxycholic Acid Is Associated With Decreased Rate of AMD.","authors":"Kevin R Zhang, Rohini M Nair, Yineng Chen, Fangming Jin, Joshua L Dunaief, Brian L VanderBeek","doi":"10.1016/j.clinthera.2025.08.010","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.010","url":null,"abstract":"<p><strong>Purpose: </strong>Cholelithiasis is associated with decreased risk of age-related macular degeneration (AMD). Ursodeoxycholic acid (UDCA), a bile acid used to dissolve cholesterol gallstones, has been shown to be retina-protective in several mouse models. This study sought to determine if UDCA may protect against AMD.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using data between January 1, 2000 to June 30, 2022 in Optum's de-identified Clinformatics Data Mart database. All patients had a history of cholelithiasis, cholecystitis, or cholecystectomy. The exposed cohort included patients taking UDCA. Controls did not take UDCA and were matched 1:3 for age (±3 years), sex, race, type of gallbladder disease, and insurance coverage start and end date (±4 months). All included patients were 55 years old or older, had at least two years of data in the dataset, and no prior history of AMD. Inverse probability of treatment weighting (IPTW) was used to balance covariates at baseline. Cox proportional hazard regression modeling with IPTW was used to compare progression to AMD between the cohorts.</p><p><strong>Findings: </strong>A total of 5,863 patients taking UDCA and 17,164 matched controls were analyzed. In both cohorts after IPTW, roughly 56% of patients had cholelithiasis, 16% had cholecystitis, and 28% had cholecystectomy. Age and sex were balanced at baseline between cohorts (UDCA: 70.5 ± 9.54 years old and 58.6% female; controls: 70.3 ± 9.59 years old and 57.4% female). In the UDCA cohort, 384/5,705 (6.74%) were diagnosed with AMD. In the control cohort, 1,559/17,322 (9.00%) were diagnosed with AMD. This corresponded to a significantly decreased hazard of AMD (adjusted hazard ratio = 0.65, 95% CI: 0.58-0.74, P < 0.0001).</p><p><strong>Implications: </strong>UDCA was associated with a 35% reduction in the hazard of AMD in patients with underlying gallbladder disease. Determining the mechanism for this protective effect could improve understanding of AMD pathogenesis. These results also suggest that clinical trials evaluating the use of UDCA for AMD could be valuable.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissolution of Once-Nightly Sodium Oxybate in Soft Foods and Alternative Liquid Reconstitution Vehicles.","authors":"Maggie Lavender, Anne Marie Morse, Bahador Mark Tafazoli, Feri Ascencion, Ellen Wermter, Laura B Herpel, Jennifer Gudeman, William John Schaefer, Jason Vaughn","doi":"10.1016/j.clinthera.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.004","url":null,"abstract":"<p><strong>Purpose: </strong>Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness (EDS) and can occur with or without cataplexy. Once-nightly sodium oxybate (ON-SXB) is approved for the treatment of cataplexy or EDS in patients 7 years of age or older with narcolepsy. ON-SXB contains both immediate-release and pH-dependent, controlled-release granules designed to be reconstituted in water and administered orally once at bedtime. This study evaluated the dissolution profile of ON-SXB after reconstitution with soft foods and alternative liquid vehicles compared to water.</p><p><strong>Methods: </strong>ON-SXB 4.5 g and 9 g were reconstituted in soft foods (lemon pudding, low-fat vanilla yogurt, and applesauce) or liquid vehicles (raspberry lemonade solution, fruit punch solution, and alkaline water). Milli-Q water served as the control. Acceptance criteria for product specifications required 40% to 60%, 42% to 62%, and ≥80% dissolution at 15 minutes, 2 hours, and 4 hours, respectively.</p><p><strong>Findings: </strong>For ON-SXB 4.5 g and 9 g, respectively, mean dissolution at 15 minutes was 48% and 45% for lemon pudding, 50% and 50% for low-fat vanilla yogurt, 49% and 48% for applesauce, 51% and 50% for raspberry lemonade solution, 51% and 51% for fruit punch solution, and 49% and 51% alkaline water; at 2 hours, 50% and 51% for lemon pudding, 51% and 50% for low-fat vanilla yogurt, 50% and 49% for applesauce, 51% and 51% for raspberry lemonade solution, 50% and 51% fruit punch solution, and 50% and 51% alkaline water; and at 4 hours, 96% and 94% for lemon pudding, 91% and 88% for low-fat vanilla yogurt, 95% and 87% for applesauce, 97% and 88% for raspberry lemonade solution, 96% and 89% for fruit punch solution, and 92% and 87% for alkaline water. All tested vehicles met acceptance criteria with ON-SXB 4.5 g and 9 g.</p><p><strong>Implications: </strong>Lemon pudding, low-fat vanilla yogurt, applesauce, raspberry lemonade solution, fruit punch solution, and alkaline water are viable reconstitution alternatives and maintain the drug dissolution characteristics of ON-SXB when compared to water. Flexibility in the administration of ON-SXB may improve narcolepsy management, enhance medication adherence, and support medication persistency.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constructive Critique on \"Efficacy and Safety of Nintedanib in Japanese Patients With Early-Stage Idiopathic Pulmonary Fibrosis: A One-Year Interim Analysis from a Multicenter Observational Study in Kyushu and Okinawa, Japan\".","authors":"Parth Aphale, Himanshu Shekhar, Shashank Dokania","doi":"10.1016/j.clinthera.2025.08.009","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.009","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Polypharmacy and Drug-Drug Interactions in a Large Cohort of Direct Oral Anticoagulant Users With Atrial Fibrillation.","authors":"Veronica De Angelis, Ylenia Ingrasciotta, Maria Carelli, Alberto Spadotto, Martina Amadori, Claudia Pagliaro, Annalisa Di Giorgio, Valentina Isgrò, Saveria Serena Foti, Michele Tari, Igor Diemberger","doi":"10.1016/j.clinthera.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.007","url":null,"abstract":"<p><strong>Purpose: </strong>Despite their promising safety profile, use of direct oral anticoagulants (DOACs) presents challenges, particularly concerning polypharmacy and potential drug-drug interactions (DDIs). This study aimed to investigate real-world effects of polypharmacy and DDIs among DOAC users, focusing on patients with atrial fibrillation (AF).</p><p><strong>Methods: </strong>A retrospective cohort analysis was conducted using administrative health care data from the Caserta Local Health Unit (2012-2020). Incident DOAC users were categorized by type of anticoagulant (apixaban, dabigatran, rivaroxaban, and edoxaban). Polypharmacy and DDIs were analyzed before and after index date (ID), stratifying results by DOAC and therapeutic indication. The impact of DDIs on safety outcomes, particularly bleeding risk, was assessed. Bleeding outcomes were evaluated within 1 year after ID by multivariate regression models.</p><p><strong>Findings: </strong>Among 16,367 incident DOAC users, 68.9% were treated for AF. The number of interacting drugs increased in 55.2% of patients, with a higher prevalence of 3+ interacting drugs in low-dose users (35% vs 29.2% in high-dose users; P < 0.05). Before ID, 35.6% of the overall cohort had 0 interacting drugs compared with 15.2% after ID. Dabigatran users had the highest increase in interacting drugs (61.8%) compared with anti-Xa agents (56%). Patients with 6+ interacting drugs exhibited a 2.5% incidence of major bleeding after ID. Dabigatran use and low-dose DOAC regimens were independently associated with increased bleeding risks.</p><p><strong>Implications: </strong>Polypharmacy and DDIs are prevalent among real-world DOAC users, particularly in patients with AF. The observed association between DDIs and bleeding risk underscores the importance of personalized medication management strategies and routine DDI evaluations to optimize DOAC safety.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}