Cts-Clinical and Translational Science最新文献

{"title":"Pharmacokinetic Profiles of Lansoprazole in Patients With Morbid Obesity Post-Roux-en-Y Gastric Bypass Surgery","authors":"Suthep Udomsawaengsup,&nbsp;Sathienrapong Chantawibul,&nbsp;Naranon Boonyuen,&nbsp;Sarunnuch Panyavorakhunchai,&nbsp;Pattharasai Kachornvitaya,&nbsp;Wasu Wisanuyothin,&nbsp;Pittawat Somvanapanich,&nbsp;Warittha Lertwatthiphong,&nbsp;Napatsanan Tanathitiphuwarat,&nbsp;Pajaree Chariyavilaskul","doi":"10.1111/cts.70200","DOIUrl":"https://doi.org/10.1111/cts.70200","url":null,"abstract":"<p>Data on the effects of Roux-en-Y gastric bypass (RYGB) surgery on lansoprazole pharmacokinetics in morbidly obese patients are limited. This study aimed to evaluate the impact of RYGB surgery on the pharmacokinetic profile of lansoprazole in Thai morbidly obese patients. Participants received 30 mg of lansoprazole twice daily for 7 days before surgery and continued the regimen for 6 weeks post-surgery. Plasma lansoprazole concentrations were measured at predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 h after dosing, both pre- and post-surgery, using a validated high-performance liquid chromatography technique. <i>CYP2C19</i> genotyping classified participants as normal metabolizers (<i>*1</i>/<i>*1</i>) or intermediate metabolizers (<i>*1</i>/<i>*2</i> and <i>*1</i>/<i>*3</i>). Pharmacokinetic parameters, including the area under the plasma concentration-time curve from 0 to 8 h (AUC_0–8 h), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax), were compared before and after surgery. A total of 13 patients (mean age 37.0 ± 3.9 years; body mass index 54.0 ± 4.8 kg/m²) were enrolled. Post-surgery, AUC_0–8 h and Cmax decreased by 16% (<i>p</i> = 0.009) and 31% (<i>p</i> = 0.003), respectively, while Tmax remained unchanged. A 30% reduction in Cmax (<i>p</i> = 0.007) was observed in <i>CYP2C19</i> normal metabolizers, whereas no significant changes were noted in intermediate metabolizers. In conclusion, RYGB surgery significantly reduced lansoprazole systemic exposure, particularly in <i>CYP2C19</i> normal metabolizers. Further studies are needed to explore the clinical implications of these pharmacokinetic changes and develop optimized treatment strategies for post-RYGB patients.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: TCTR20220118001</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638677","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":"Perspectives on Using Pharmacogenomics to Guide Tobacco Cessation: Survey Results From an American Indian Community","authors":"Madeline L. Wichman,&nbsp;Daniela M. Wall,&nbsp;Suzanna S. Garcia Mota,&nbsp;Shayna R. Killam,&nbsp;Karen E. Brown,&nbsp;Kaja Aagaard,&nbsp;Juanita Swaney,&nbsp;LeeAnna I. Muzquiz,&nbsp;Bernadette N. Corum,&nbsp;Katrina G. Claw,&nbsp;Erica L. Woodahl","doi":"10.1111/cts.70194","DOIUrl":"https://doi.org/10.1111/cts.70194","url":null,"abstract":"<p>Pharmacogenomics research has predominantly focused on populations of European ancestry, limiting the application to diverse populations such as American Indian and Alaska Native (AIAN) communities. Our community-centric study aims to understand perspectives on utilizing pharmacogenomics to guide tobacco cessation in an AIAN community using a survey with qualitative and quantitative components. We assessed participant (<i>n =</i> 273) tobacco usage and cessation history, pharmacogenomics knowledge, and perceptions of utilizing pharmacogenomics in the context of tobacco cessation. We found that the majority of participants (92%) were aware of the risks associated with tobacco usage and believed it to be a problem within their community (76%). Our results showed that 29% of participants had some level of knowledge regarding pharmacogenomics and only 6% had previously participated in pharmacogenomics research, demonstrating the need for further education and awareness. Community involvement was a priority for participants, with 64% preferring Tribal inclusion in all research stages and 63% favoring partnerships with local health centers. We also found support for future research, with 68% viewing pharmacogenomics as a beneficial tool. Concerns were raised regarding the handling of genetic material and result dissemination, emphasizing the importance of ethical research practices, transparent communication, and community partnership. Our findings serve as a foundation for shaping future research efforts and developing a framework for implementing tobacco cessation interventions. Our community-centered approach addresses the specific needs of this AIAN community and offers insights applicable to research practices within other underserved and marginalized populations, particularly those with a historical distrust of research.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602786","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":"First-In-Human Safety, Tolerability, and Pharmacokinetics of PPI-1011, a Synthetic Plasmalogen Precursor","authors":"Tara Smith,&nbsp;Kaeli J. Knudsen,&nbsp;Shawn A. Ritchie","doi":"10.1111/cts.70195","DOIUrl":"https://doi.org/10.1111/cts.70195","url":null,"abstract":"<p>PPI-1011 is a synthetic plasmalogen precursor designed to augment plasmalogen levels in patients with Rhizomelic chondrodysplasia punctata (RCDP), an ultra-rare genetic disorder caused by a plasmalogen deficiency that results in significant physical and mental delays. We report here a Phase I, randomized, double-blind, placebo-controlled study that evaluated the safety, tolerability, and pharmacokinetics (PK) of single (10–100 mg/kg) and multiple (75 and 100 mg/kg/day) ascending doses of PPI-1011 in healthy adults. All treatment-emergent adverse events (TEAEs) were mild, monitorable, and resolved without intervention, suggesting no significant safety concerns. The most common TEAEs were gastrointestinal in both the placebo and PPI-1011 groups, suggesting they were likely related to the oil-based nature of the formulation. PK analysis confirmed that both single (25, 50, 75 and 100 mg/kg) and multiple-dose (75 and 100 mg/kg, once daily) administration of PPI-1011 significantly increased serum levels of the target plasmalogen (PlsEtn 16:0/22:6). With a once-daily regimen, PPI-1011 administration resulted in a sustained increase of PlsEtn 16:0/22:6 serum concentrations in healthy participants over a duration of 14 days and beyond.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622473","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":"Evaluating the Effect of Epigallocatechin Gallate (EGCG) in Reducing Folate Levels in Reproductive Aged Women by MTHFR and DHFR Genotype in Combination With Letrozole or Clomiphene","authors":"Jeremy J. Johnson,&nbsp;Hiba Siblini,&nbsp;Ayman Al-Hendy,&nbsp;James H. Segars,&nbsp;Frank González,&nbsp;Hugh S. Taylor,&nbsp;Bhuchitra Singh,&nbsp;Sandra A. Carson,&nbsp;Gregory M. Christman,&nbsp;Hao Huang,&nbsp;Bikash Dangi,&nbsp;Heping Zhang","doi":"10.1111/cts.70189","DOIUrl":"https://doi.org/10.1111/cts.70189","url":null,"abstract":"<p>Previous epidemiological studies have suggested that green tea catechins, including Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, may be associated with reduced serum folate levels. This is of particular interest as women of childbearing age may be consuming EGCG from tea, dietary supplements, or involved in active clinical trials studying EGCG or green tea extract. EGCG was reported to shrink uterine fibroids in preclinical and clinical studies. This observation led to the development of a multicenter NICHD-funded clinical trial to evaluate the safety of EGCG for treating women with fibroids and unexplained infertility (NCT04177693). To answer the question of whether green tea extract standardized to EGCG led to a reduction in folate, 39 women aged ≥ 18 to ≤ 40 years, with/without uterine fibroids, were evaluated. These women were randomized to receive either EGCG, EGCG + clomiphene, or EGCG + letrozole for 30 days. A daily dose of 720 mg of highly characterized green tea extract containing EGCG was used. Participants were genotyped for polymorphisms at positions 677 and 1298 in MTHFR and for the −19 bp deletion polymorphism of DHFR. During the intervention with EGCG, folate levels remained in the normal range in all subjects. Our data suggest that in reproductive-age women, a 30-day course of EGCG 720 mg daily taken alone or in combination with clomiphene citrate or letrozole (for 5 days) is well-tolerated and is not associated with folate deficiency even in the presence of MTHFR and/or DHFR polymorphisms known to negatively impact folate synthesis.</p><p><b>Trial Registration:</b> Clinical trial: NCT 01311869</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602579","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":"Psoriasis Risk Is Lower in Type 2 Diabetes Patients Using Dipeptidyl Peptidase-4 Inhibitors or Thiazolidinediones Compared to Sulfonylureas","authors":"Wei-Sheng Chen,&nbsp;Tzu-Min Lin,&nbsp;Yu-Sheng Chang,&nbsp;Yu-Chuan Shen,&nbsp;Hui-Ching Hsu,&nbsp;Tzu-Tung Kuo,&nbsp;Shu-Chuan Chen,&nbsp;Jin-Hua Chen,&nbsp;Chi-Ching Chang","doi":"10.1111/cts.70177","DOIUrl":"https://doi.org/10.1111/cts.70177","url":null,"abstract":"<p>The risk of psoriasis in diabetic patients has rarely been explored. This study aims to compare the risk of incident psoriasis in patients with Type 2 diabetes (T2D) who initiate dipeptidyl peptidase-4 inhibitors (DPP-4is) or thiazolidinediones (TZDs) with those who initiate sulfonylureas, the most common second-line glucose-lowering therapy, in addition to metformin monotherapy. This sequential, propensity-score-matched, new-user comparative effectiveness study utilized a target trial emulation framework. It included adults with T2D receiving metformin monotherapy, using data from 2006 to 2015 from a general population database in Taiwan. The primary outcome was the incidence of psoriasis, determined through diagnoses recorded in urgent care, hospital, and outpatient department records. Cox proportional hazards and Poisson regressions with 1:4 propensity score matching was employed to evaluate the risk factors for psoriasis after adjusting for comorbidities and the use of other medications. In 49,810 propensity score-matched adults with T2D (27,630 men [55.4%]; mean age 57.5 years) identified in the database, the incidence rate of psoriasis in DPP-4i users was 188 cases per 100,000 person-years, lower than in sulfonylurea users (467 cases per 100,000 person-years), with a hazard ratio(HR) of 0.422 (95% CI, 0.273–0.716). For the TZD vs. sulfonylurea comparison, the HR was 0.35, but the smaller matched dataset resulted in wide confidence intervals. The findings suggest that the use of DPP-4is is associated with a lower risk of psoriasis compared to sulfonylureas in patients with T2D. These results can guide the selection of glucose-lowering therapies in T2D patients who are at risk of developing psoriasis.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602665","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":"Assessment of Food Effect and pH-Dependent Drug–Drug Interactions of Fruquintinib in Healthy Subjects","authors":"Martha Gonzalez,&nbsp;Zhao Yang,&nbsp;William R. Schelman,&nbsp;Xiaofei Zhou,&nbsp;Neeraj Gupta,&nbsp;Caly Chien","doi":"10.1111/cts.70168","DOIUrl":"https://doi.org/10.1111/cts.70168","url":null,"abstract":"<p>This two-sequence, three-period study (NCT04645940) was designed to evaluate the effect of food and concomitant rabeprazole, a proton pump inhibitor, on the pharmacokinetics (PK) and safety of fruquintinib and its metabolite M11 after a single oral dose of fruquintinib 5 mg in healthy subjects. In the food effect treatment periods, 14 subjects were randomized in a 1:1 ratio utilizing a two-sequence (fed/fasted vs. fasted/fed), two-period, cross-over design. Fruquintinib was administered on Day 1 (Period 1) and Day 15 (Period 2). In the drug-interaction period (Period 3), all subjects received rabeprazole 40 mg 1 h prior to fruquintinib under fasted conditions, following a 6-day lead-in of rabeprazole 40 mg once daily. PK samples to measure fruquintinib and M11 were collected pre-dose and over 168 h after fruquintinib dosing. Administration of fruquintinib with a high-fat meal resulted in similar systemic exposure compared with fasted conditions. In addition, coadministration of fruquintinib with rabeprazole resulted in similar exposure compared with fruquintinib alone. For both evaluations, 90% confidence intervals for the ratio of geometric least square mean of the area under the curve and peak concentration for fruquintinib and M11 were entirely within 80%–125% bounds. The study results showed no effects of food or rabeprazole on fruquintinib PK, and support that fruquintinib can be taken without regard to food or concurrent gastric acid-reducing agents.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602580","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":"Establishing a Common Lexicon for Circulating Tumor DNA Analysis and Molecular Residual Disease: Insights From the BLOODPAC Consortium","authors":"Andrew G. Hadd,&nbsp;Angela Silvestro,&nbsp;Brittany Avin McKelvey,&nbsp;Jonathan Baden,&nbsp;Christina Bormann Chung,&nbsp;Ben Brown,&nbsp;Fernando Cruz-Guilloty,&nbsp;James Godsey,&nbsp;Gregory Jones,&nbsp;Cheng-Ho Jimmy Lin,&nbsp;Dorys Lopez Ramos,&nbsp;Daniel Norton,&nbsp;Melanie R. Palomares,&nbsp;Carol Pena,&nbsp;Thereasa Rich,&nbsp;Angel Rodriguez,&nbsp;Mark Stewart,&nbsp;Diana Merino Vega,&nbsp;Lauren C. Leiman","doi":"10.1111/cts.70185","DOIUrl":"https://doi.org/10.1111/cts.70185","url":null,"abstract":"<p>The use of a liquid biopsy to assess molecular residual disease (MRD) of solid tumors holds significant promise for improving outcomes for patients with cancer. Liquid biopsies are a minimally invasive approach for the identification of circulating tumor biomarkers through a simple blood sample. Assays capable of detecting MRD through analysis of circulating tumor DNA (ctDNA) are rapidly evolving for clinical study applications and therapeutic interventions. To address these opportunities, BLOODPAC—a multi-disciplinary consortium representing stakeholders from public, industry, academia, and regulatory agencies—formulated a lexicon that provides a shared framework and clear definitions using liquid biopsies for solid tumor MRD with an emphasis on ctDNA detection. The terms in the lexicon are categorized under general MRD, ctDNA testing methodologies, reporting results, and acquisition timepoints, including examples of current and potential clinical use cases for MRD tests. The overall goal is to provide a unified language and approaches to solid tumor MRD to advance applications of these technologies, allow data aggregation to strengthen future evidence, and facilitate regulatory approvals, leading to the use of liquid biopsy as an early endpoint in clinical trials. We believe that a common set of terminology and methods for solid tumor MRD can improve understanding and appropriate use of testing, accelerate clinical development, and improve outcomes for cancer patients.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602769","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":"A Tutorial and Use Case Example of the eXtreme Gradient Boosting (XGBoost) Artificial Intelligence Algorithm for Drug Development Applications","authors":"Matthew Wiens,&nbsp;Alissa Verone-Boyle,&nbsp;Nick Henscheid,&nbsp;Jagdeep T. Podichetty,&nbsp;Jackson Burton","doi":"10.1111/cts.70172","DOIUrl":"https://doi.org/10.1111/cts.70172","url":null,"abstract":"<p>Approaches to artificial intelligence and machine learning (AI/ML) continue to advance in the field of drug development. A sound understanding of the underlying concepts and guiding principles of AI/ML implementation is a prerequisite to identifying which AI/ML approach is most appropriate based on the context. This tutorial focuses on the concepts and implementation of the popular eXtreme gradient boosting (XGBoost) algorithm for classification and regression of simple clinical trial-like datasets. Emphasis is placed on relating the underlying concepts to the code implementation. In doing so, the aim is for the reader to gain knowledge about the underlying algorithm and become better versed with how to implement the algorithm functions for relevant clinical drug development questions. In turn, this will provide practical ML experience which can be applied to algorithms and problems beyond the scope of this tutorial.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595589","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":"Buprenorphine's Effect on the Human Immune System and Inflammation","authors":"Samuel D. Shin,&nbsp;Rachel Branning,&nbsp;Michele McGinnis,&nbsp;Alexandra Shin,&nbsp;Ming-Fen Ho,&nbsp;Victor M. Karpyak,&nbsp;Tyler Oesterle","doi":"10.1111/cts.70180","DOIUrl":"https://doi.org/10.1111/cts.70180","url":null,"abstract":"<p>Opioid use disorder is a persistent epidemic despite several FDA-approved medications for its treatment. While the pathogenesis of opioid use disorder has been classically attributed to dopamine pathways in the brain, there is emerging evidence and interest surrounding the role of inflammation and inflammatory signaling in its development and treatment. Buprenorphine has become the most prescribed medication for opioid use disorder, largely due to its ease of access and tolerability. This review aimed to better characterize contemporary knowledge of how buprenorphine modulates the human immune system and inflammatory functions in this population. A comprehensive review was conducted using 11 key databases, including Embase, MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. This review captured 8177 records, and 14 studies were ultimately selected for inclusion and discussion in this review. Notably, all 14 clinical studies evaluated buprenorphine's effect on the peripheral immune system, and the majority of the studies supported the notion that initiation and maintenance of buprenorphine restore immune suppression caused by opioid use disorder. In addition, we discuss how recent and ongoing work utilizing advanced imaging and cellular technologies is advancing the understanding of how buprenorphine affects the immune and inflammatory signaling in the brain.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595229","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":"Safety, Tolerability, and Pharmacokinetics of SC1011 (Sufenidone), a Novel Antifibrotic Small Molecule, in Phase 1 Studies in Healthy Subjects","authors":"Yun Liu,&nbsp;Xiaoning Chen,&nbsp;Huimin Tang,&nbsp;Fan Jiang,&nbsp;Yaqin Tang,&nbsp;Huijuan Zhu,&nbsp;Yanping Du,&nbsp;Hongjie Qian,&nbsp;Shuyun Liu,&nbsp;Xiaoshu Sun,&nbsp;Bin Zan,&nbsp;Yuexia Zeng,&nbsp;Yun Li,&nbsp;Zhen Ge,&nbsp;Yongguo Li,&nbsp;Zhongqi Yang","doi":"10.1111/cts.70179","DOIUrl":"https://doi.org/10.1111/cts.70179","url":null,"abstract":"<p>SC1011 (sufenidone) is a novel pyridone derivative with therapeutic potential for idiopathic pulmonary fibrosis (IPF). Two Phase 1 studies evaluated the safety and pharmacokinetics of single (SAD) and multiple ascending doses (MAD) of SC1011 immediate-release (IR) and modified-release (MR) oral formulations in healthy adult subjects. In Phase 1a, subjects were randomized to receive oral SC1011 IR or placebo in SAD (50 mg-300 mg) or MAD (100 mg and 200 mg) twice daily for 7 days. The Phase 1b study consisted of three treatment groups that received 100, 150, or 200 mg SC1011 MR twice daily for 7 days. SC1011 IR was absorbed rapidly (mean time to maximum concentration, T_max ≤ 1 h) and eliminated rapidly (mean terminal half-life, t_1/2: 1.23–2.64 h) following 50–300 mg single-dose administrations. Reduced maximum plasma concentration (C_max), delayed T_max, and comparable total exposure were observed with the MR formulation compared with the IR formulation. Both formulations demonstrated dose-proportional pharmacokinetics at the applied dose ranges, and no obvious accumulation of systemic exposure was observed upon repeated administration. All treatment-emergent adverse events (TEAEs) with both formulations were mild or moderate in severity, and gastrointestinal reactions were the most frequently reported TEAEs. The tolerability of SC1011 was markedly improved with the MR formulation. Exposure–adverse event (AE) analysis with the most frequent AEs identified C_max rather than total exposure as a good predictor of AEs. Compared to the IR formulation, SC1011 MR demonstrated improved exposure and tolerability, supporting its further development in patients with IPF.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594847","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}