Expert opinion on investigational drugs最新文献

The first-in-human study of QHRD106 functioning as a safe and effective long-acting kallikrein drug potentially aiding ischemic stroke. QHRD106作为一种安全有效的长效降凝血酶药物，可能有助于缺血性中风，这是首次进行人体研究。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-11-19 DOI: 10.1080/13543784.2024.2430200

Lei Huang, Runbin Sun, Hengwen Song, Zhiyou Chen, Yuxin Hong, Haoyi Yang, Yuwen Zhang, Lijun Wei, Fei Fei, Juan Li

{"title":"The first-in-human study of QHRD106 functioning as a safe and effective long-acting kallikrein drug potentially aiding ischemic stroke.","authors":"Lei Huang, Runbin Sun, Hengwen Song, Zhiyou Chen, Yuxin Hong, Haoyi Yang, Yuwen Zhang, Lijun Wei, Fei Fei, Juan Li","doi":"10.1080/13543784.2024.2430200","DOIUrl":"10.1080/13543784.2024.2430200","url":null,"abstract":"Background: This study assessed the pharmacokinetics (PK), pharmacodynamics (PD) and safety of QHRD106, and made a comparison with urinary kallindinogenase (UKN) in healthy volunteers.Methods: This study comprised a randomized, double-blind, placebo-controlled, single-dose escalation phase and an open-label, multiple-dose escalation phase. Ninety-four subjects received intramuscular injections of QHRD106/placebo only once and 30 subjects received QHRD106 four times. Six subjects received 0.15 PNA units UKN intravenously for 7 d. PK and PD analysis were conducted by using a electrochemiluminescent assay and a liquid chromatography/mass spectrometry methodology, respectively. Cerebral circulation was assessed by the magnetic resonance imaging system.Results: QHRD106 exhibited a slow absorption profile in the human body. Compared to UKN, QHRD106-induced changes in bradykinin concentration later, but with a noticeably prolonged duration. Compared to baseline, cerebral blood flow exhibited a significant improvement on d 7 after a single dose of 18,900 IU and an improvement from d 2 to d 14 after multiple doses of 8400 IU of QHRD106. QHRD106 appeared generally good safety and no severe adverse events occurred in all the groups.Conclusions: This study provided initial evidence of potential treatment for ischemic strokes that the QHRD106 injection functioned as a safe and effective long-acting kallikrein drug.Registration: This study was registered on ClinicalTrials.gov with the identifier NCT06380699 and NCT06388772.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-9"},"PeriodicalIF":4.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Promising selective progesterone receptor modulators: what's new in female contraception? 前景看好的选择性孕酮受体调节剂：女性避孕的新动向？

IF 5.4 2区医学

Expert opinion on investigational drugs Pub Date : 2024-11-18 DOI: 10.1080/13543784.2024.2422838

Anita Nelson, Marit Pearlman Shapiro

{"title":"Promising selective progesterone receptor modulators: what's new in female contraception?","authors":"Anita Nelson, Marit Pearlman Shapiro","doi":"10.1080/13543784.2024.2422838","DOIUrl":"10.1080/13543784.2024.2422838","url":null,"abstract":"Introduction: Selective progesterone receptor modulators (SPRMs), such as mifepristone and ulipristal acetate (UPA), have demonstrated high efficacy and safety as single-dose treatments for medication abortion and emergency contraception (EC). Other obstetrical and gynecologic applications have emerged, both for episodic and ongoing uses. The potential of these compounds to provide estrogen-free, ongoing contraception is promising; however, the rare, but serious, hepatic injury cases seen with UPA have put at least a temporary halt to further research in this area.Areas covered: This paper reviews the biophysical impacts and clinical applications of SPRMs in women's reproductive health, with a focus on the roles of mifepristone and UPA in family planning. Given the political environment, especially in the United States where these applications may be threatened, extensive description is dedicated to mechanisms of action of these agents.Expert opinion: Both mifepristone and ulipristal acetate are first-line options for single-use applications. There continues to be a need for estrogen-free ongoing contraception that does not have unpopular impacts on bleeding caused by contraceptive methods and for treatments for heavy menstrual bleeding. However, current restrictions on UPA limit longer term use. Perhaps other SPRMs without hepatic impacts may emerge to fill this need.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-12"},"PeriodicalIF":5.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting a key FAK-tor: the therapeutic potential of combining focal adhesion kinase (FAK) inhibitors and chemotherapy for chemoresistant non-small cell lung cancer. 靶向关键的FAK-tor：结合焦点粘附激酶（FAK）抑制剂和化疗治疗化疗耐药非小细胞肺癌的治疗潜力。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-10-22 DOI: 10.1080/13543784.2024.2417762

Emma Geijerman, Francesca Terrana, Godefridus J Peters, Dongmei Deng, Patrizia Diana, Elisa Giovannetti, Geng Xu

{"title":"Targeting a key FAK-tor: the therapeutic potential of combining focal adhesion kinase (FAK) inhibitors and chemotherapy for chemoresistant non-small cell lung cancer.","authors":"Emma Geijerman, Francesca Terrana, Godefridus J Peters, Dongmei Deng, Patrizia Diana, Elisa Giovannetti, Geng Xu","doi":"10.1080/13543784.2024.2417762","DOIUrl":"https://doi.org/10.1080/13543784.2024.2417762","url":null,"abstract":"Introduction: NSCLC is the leading cause of cancer-related deaths globally, with a low survival rate primarily due to NSCLC frequently becoming chemoresistant. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in pathways regulating multiple processes in the cell, including survival, migration, and the TME, that contribute to both tumor progression and drug resistance. Recently, FAK inhibitors (FAKi) have shown promising potential for the treatment of NSCLC.Areas covered: This narrative review aims to summarize key signaling pathways involving FAK that contribute to tumor progression and drug resistance. It will further provide an overview of FAKi currently in pre- and early-phase clinical trials for solid tumors, as well as the therapeutic potential of combining FAKi with chemotherapy, as this has emerged as a promising strategy to overcome chemoresistance in NSCLC.Expert opinion: It is becoming increasingly clear that FAK is not an oncogenic driver but rather contributes to tumor progression and drug resistance. Hence, while FAKi have only demonstrated modest results in clinical trials when given by themselves, treatment regimens combining other therapies with FAKi have shown promising potential to overcome drug resistance. Lastly, of particular novelty are FAK-PROTACs (proteolysis-targeting chimaeras), which uniquely target both cytosolic and nuclear FAK.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-16"},"PeriodicalIF":4.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual blockade of endothelin A and angiotensin II type 1 receptors with sparsentan as a novel treatment strategy to alleviate IgA nephropathy. 用司帕生坦双重阻断内皮素 A 和血管紧张素 II 1 型受体，作为缓解 IgA 肾病的新型治疗策略。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-10-18 DOI: 10.1080/13543784.2024.2414902

Hajime Nagasawa, Hitoshi Suzuki, Seiji Ueda, Yusuke Suzuki

{"title":"Dual blockade of endothelin A and angiotensin II type 1 receptors with sparsentan as a novel treatment strategy to alleviate IgA nephropathy.","authors":"Hajime Nagasawa, Hitoshi Suzuki, Seiji Ueda, Yusuke Suzuki","doi":"10.1080/13543784.2024.2414902","DOIUrl":"https://doi.org/10.1080/13543784.2024.2414902","url":null,"abstract":"Introduction: Although immunoglobulin A nephropathy (IgAN) had been discovered more than 50 years ago, 30-40% of IgAN patients still have primary glomerular disease that progresses to end-stage renal disease. However, various treatment strategies for IgAN have rapidly expanded in recent years to include endothelin (ET) receptor antagonists.Areas covered: In this review, we discuss the role of the ET-1/ETA receptor axis in the development of IgAN, especially focusing on the potential of sparsentan, a dual ET and angiotensin receptor antagonist as a novel therapy for IgAN.Expert opinion: Evaluation of the MEST-C score at the time of renal biopsy in IgAN is important in determining treatment strategies. If lesions are mainly in the acute phase, such as crescents, steroid therapy should be continued. However, if lesions are mainly in the chronic phase, such as glomerulosclerosis, sparsentan rather than steroid or angiotensin II receptor blocker alone may improve renal outcomes. Although further clinical studies are needed to back up these assumptions, appropriate combination of new drugs containing sparsentan and conventional drugs for IgAN treatment at the appropriate disease stage is expected to further inhibit the progression of renal damage.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-10"},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Management of inflammaging in kidney diseases: focusing on the current investigational drugs. 肾脏疾病的炎症管理：关注当前的研究药物。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-10-16 DOI: 10.1080/13543784.2024.2417755

Vishwadeep Shelke, Neha Dagar, Maciej Lech, Anil Bhanudas Gaikwad

{"title":"Management of inflammaging in kidney diseases: focusing on the current investigational drugs.","authors":"Vishwadeep Shelke, Neha Dagar, Maciej Lech, Anil Bhanudas Gaikwad","doi":"10.1080/13543784.2024.2417755","DOIUrl":"https://doi.org/10.1080/13543784.2024.2417755","url":null,"abstract":"Introduction: To improve kidney disease treatments, it is crucial to understand how inflammaging affects patients´ longevity. We could potentially slow down kidney disease progression and enhance longevity by targeting specific pathways involved in inflammaging with potential drugs.Areas of covered: This review offers an updated overview of 'anti-inflammaging' drugs currently in the kidney disease research pipeline, as well as those with potential for future therapeutic use. Furthermore, these drugs are categorized according to their mechanisms, including targeting inflammation, immune and metabolic regulation, oxidative stress, senescence, and autophagy, as demonstrated in preclinical and early clinical trials. Additionally, the review provides insights into key challenges and opinions for future advancements in this field.Expert opinion: We reviewed recent advancements in applying different therapies to mitigate inflammaging in kidney diseases. We underscore the need for continued research to elucidate the complex pathways underlying inflammaging, which will be essential for the development of more precise and effective treatments. As research in this field advances, several emerging drugs appear promising for future investigation. While current findings are encouraging, further clinical studies are required to validate the therapeutic potential of these agents in kidney diseases, ultimately paving the way for more targeted and efficacious interventions.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-14"},"PeriodicalIF":4.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein phosphatase 2A activators under investigation for smoking-related chronic obstructive pulmonary disease and related disorders. 正在研究用于治疗与吸烟有关的慢性阻塞性肺病和相关疾病的蛋白磷酸酶 2A 激活剂。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-10-15 DOI: 10.1080/13543784.2024.2416982

Sabina Antoniu, Setfan Rascu

{"title":"Protein phosphatase 2A activators under investigation for smoking-related chronic obstructive pulmonary disease and related disorders.","authors":"Sabina Antoniu, Setfan Rascu","doi":"10.1080/13543784.2024.2416982","DOIUrl":"https://doi.org/10.1080/13543784.2024.2416982","url":null,"abstract":"Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation during therapy. Cystic fibrosis (CF), alpha-one antitrypsin deficiency (AATD), and non-CF bronchiectasis are also chronic respiratory disorders with inflammation and progression that share many similarities with COPD. Therefore, various anti-inflammatory approaches are currently being investigated, and protein phosphatase 2A (PP2A) activators may represent one such approach.Areas covered: Systematic review of papers published from 2000-to date on the anti-inflammatory role of endogenous PP2A, the consequences of its inhibition by smoking, and the beneficial effects of its activation in COPD.Expert opinion: PP2A activation is a plausible therapeutic approach in COPD and related disorders, such as CF, AATD, and non-CF bronchiectasis, although the available evidence is still mostly experimental. Metformin repurposing and consideration of inhalation for some of the molecules discussed in this study are promising approaches.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-8"},"PeriodicalIF":4.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Theranostic strategies in sarcoma: preliminary clinical evidence. 肉瘤的血清疗法策略：初步临床证据。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-10-09 DOI: 10.1080/13543784.2024.2414119

Luca Filippi, Cristina Ferrari, Giuseppe Rubini

{"title":"Theranostic strategies in sarcoma: preliminary clinical evidence.","authors":"Luca Filippi, Cristina Ferrari, Giuseppe Rubini","doi":"10.1080/13543784.2024.2414119","DOIUrl":"10.1080/13543784.2024.2414119","url":null,"abstract":"Introduction: Sarcomas encompass a highly diverse range of malignancies, characterized by varied morphological and molecular profiles. Treatment options in case of therapy-refractory or advanced disease are limited. In this context, theranostics emerges as an innovative platform seamlessly integrating diagnosis and therapy, offering promising prospects.Areas covered: This special report delves into the initial clinical applications of theranostic-based approaches in sarcomas. Specifically, it examines various strategies targeting biomarkers associated with sarcomas, including fibroblast activation protein (FAP), prostate-specific membrane antigen (PSMA), C-X-C chemokine receptor type 4 (CXCR4) and somatostatin receptor 2 (SSTR2).Expert opinion: The heterogeneous uptake of the CXCR4-targeted radioligand in lesions, along with its poor correlation with immunohistochemistry data, diminishes the attractiveness of this theranostic approach in the sarcoma oncological setting. SSTR2-targeted approaches in sarcoma, although potentially effective, are limited to a single case. Early experiences with FAP inhibitors in sarcoma patients have shown particularly promising outcomes, indicating effective disease control with minimal toxicity. While PSMA presents an enticing target for theranostic approaches in sarcomas, its utilization remains anecdotal and requires further investigation. Prospective and well-designed clinical trials are imperative to delineate the potential impact of FAPI- and PSMA-based approaches on sarcoma therapeutic landscapes, offering innovative and personalized treatment options.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-9"},"PeriodicalIF":4.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing the clinical potential of plozasiran, an APOC3 siRNA therapy for severe hypertriglyceridemia. 评估 APOC3 siRNA 治疗严重高甘油三酯血症的临床潜力。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-10-09 DOI: 10.1080/13543784.2024.2414126

Xuan L Tang, Amanda J Hooper, John R Burnett

引用次数: 0

A four-in-one first-in-human study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and concentration-QTc relationship of HRS-1780, a selective non-steroidal mineralocorticoid receptor antagonist, in healthy men. 这是一项四合一的首次人体试验，目的是评估 HRS-1780（一种选择性非甾体类矿物质皮质激素受体拮抗剂）在健康男性中的安全性、耐受性、药代动力学、药效学和浓度-QTc 关系。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-10-01 Epub Date: 2024-08-26 DOI: 10.1080/13543784.2024.2393867

Qi Shen, Lingzhi Li, Weilin Qian, Xue Dong, Manchen Bao, Rong Huang, Na Li, Zi Ye, Gang Cheng, Quanren Wang, Kai Shen, Zhu Luo

{"title":"A four-in-one first-in-human study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and concentration-QTc relationship of HRS-1780, a selective non-steroidal mineralocorticoid receptor antagonist, in healthy men.","authors":"Qi Shen, Lingzhi Li, Weilin Qian, Xue Dong, Manchen Bao, Rong Huang, Na Li, Zi Ye, Gang Cheng, Quanren Wang, Kai Shen, Zhu Luo","doi":"10.1080/13543784.2024.2393867","DOIUrl":"10.1080/13543784.2024.2393867","url":null,"abstract":"Background: This first-in-human study evaluated HRS-1780, an oral selective non-steroidal mineralocorticoid receptor antagonist, in healthy men.Research design and methods: In single ascending dose (SAD) part, 10 participants for each dose cohort (5, 10, 20, 40, 60, and 80 mg) were randomized (8:2) to HRS-1780 or placebo. In multiple ascending dose part, 12 participants for each dose (10, 20, and 40 mg) were randomized (9:3) to HRS-1780 or placebo once daily for 7 days. The primary endpoint was safety and tolerability.Results: HRS-1780 was well tolerated with all adverse events being mild. In the steady state, the median time to maximum concentration (Tmax) was 0.750 h and mean half-life was 1.76-1.96 h. High-fat/high-calorie meal prolonged Tmax but did not affect exposure. Multiple dosing of HRS-1780 at 40 mg showed a decreasing trend in systolic blood pressure compared with placebo. Changes in plasma aldosterone and norepinephrine with HRS-1780 were higher compared to placebo. Upper bounds of two-sided 90% confidence interval of placebo-adjusted change-from-baseline QTcF were below 10 msec at the maximum concentration in SAD. The trial had limited sample size and short study duration.Conclusions: HRS-1780 had favorable safety and pharmacokinetic profiles and did not cause clinically meaningful QTcF prolongation.Trial registration: ClinicalTrials.gov (NCT05638126).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1083-1093"},"PeriodicalIF":4.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects. 首次在健康受试者中开展人体研究，评估因子 XI 单克隆抗体 SHR-2004 的安全性、耐受性、药代动力学和药效学。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2024-10-01 Epub Date: 2024-08-22 DOI: 10.1080/13543784.2024.2391837

Tingting Ma, Zuyi Weng, Bei Cao, Yanli Dong, Chanjuan Deng, Lei Huang, Yuanxun Yang, Yuqi Wang, Chenxi Shen, Lei Wang, Kai Shen, Juan Li

{"title":"The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects.","authors":"Tingting Ma, Zuyi Weng, Bei Cao, Yanli Dong, Chanjuan Deng, Lei Huang, Yuanxun Yang, Yuqi Wang, Chenxi Shen, Lei Wang, Kai Shen, Juan Li","doi":"10.1080/13543784.2024.2391837","DOIUrl":"10.1080/13543784.2024.2391837","url":null,"abstract":"Background: Inhibiting the coagulation factor XI (FXI) is a novel strategy for prevention and treatment of thromboembolism without affecting extrinsic coagulation pathways. SHR-2004 is a humanized monoclonal antibody that selectively binds to FXI and factor XIa (FXIa).Research design & methods: This randomized, double-blind, dose-escalation, placebo-controlled study evaluated SHR-2004 administered either intravenously (i.v.; Part A) or subcutaneously (s.c.; Part B). In Part A, 24 subjects received a single i.v. dose of SHR-2004 (0.1, 0.3, or 1.0 mg/kg) or placebo. In Part B, 40 subjects received a single s.c. dose of SHR-2004 (0.5, 1.0, 3.0, or 4.5 mg/kg) or placebo.Results: SHR-2004 was well tolerated. Plasma exposure to SHR-2004 increased in a dose-dependent manner. The geometric mean half-time ranged from 11.6 to 13.0 days. FXI activity decreased, and the activated partial thromboplastin time (APTT) was prolonged after i.v. and s.c. administration in a dose- and time-dependent manner. FXI activity was nearly completely abolished immediately after administering the highest i.v. dose, with the average APTT prolonged to nearly three times of baseline.Conclusion: SHR-2004 is a promising candidate for further development as an anticoagulant drug that exerts effective anticoagulation with minimal risk of bleeding.Clinical trial registration: www.clinicaltrials.gov identifier is NCT05369767.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1075-1082"},"PeriodicalIF":4.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0