Varenicline Tartrate

注册号： Registration number： ChiCTR2600119043 最近更新日期： Date of Last Refreshed on： 2026-02-14 11:15:19 注册时间： Date of Registration： 2026-02-14 00:00:00 注册号状态： 预注册Registration Status： Prospective registration注册题目： 评价ALT001 在中国健康受试者中单、多次给药安全性、耐受性的随机、双盲、安慰剂对照，I 期临床研究Public title： A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Tolerability of Single and Multiple Doses of ALT001 in Healthy Chinese Subjects注册题目简写：English Acronym：研究课题的正式科学名称： 评价ALT001 在中国健康受试者中单、多次给药安全性、耐受性的随机、双盲、安慰剂对照，I 期临床研究Scientific title： A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Tolerability of Single and Multiple Doses of ALT001 in Healthy Chinese Subjects研究课题代号(代码)： Study subject ID：在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：申请注册联系人： 王轶伦  研究负责人： 王伊龙 Applicant： Yilun Wang  Study leader： Yilong Wang 申请注册联系人电话： Applicant telephone： +86 188 1151 6024 研究负责人电话： Study leader's telephone： +86 139 1166 6571申请注册联系人传真 ： Applicant Fax： 研究负责人传真： Study leader's fax：申请注册联系人电子邮件： Applicant E-mail： rebecca@darwincell.net 研究负责人电子邮件： Study leader's E-mail： yilong528@gmail.com申请单位网址(自愿提供)： Applicant website(voluntary supply)： 研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：申请注册联系人通讯地址： 中国北京市石景山区六工汇B1 栋 研究负责人通讯地址： 中国北京市丰台区南四环西路119号Applicant address： Building B1, Liu Gong Hui, Shougang Park, Shijingshan District, Beijing, China Study leader's address： No. 119 South Fourth Ring Road West, Fengtai District, Beijing, China申请注册联系人邮政编码： Applicant postcode： 研究负责人邮政编码： Study leader's postcode：申请人所在单位： 达尔文起航(北京)生物科技有限公司Applicant's institution： Darwin Launch (Beijing) Biotechnology Co., Ltd.研究负责人所在单位： 首都医科大学附属北京天坛医院Affiliation of the Leader： Capital Medical University Affiliated Beijing Tiantan Hospital是否获伦理委员会批准： 是Approved by ethic committee： Yes伦理委员会批件文号： Approved No. of ethic committee： YW2025-064-03 伦理委员会批件附件： Approved file of Ethical Committee： 查看附件View批准本研究的伦理委员会名称： 首都医科大学附属北京天坛医院医学伦理委员会Name of the ethic committee： Medical Ethics Committee of Beijing Tiantan Hospital, Capital Medical University伦理委员会批准日期： Date of approved by ethic committee： 2026-02-09 00:00:00伦理委员会联系人： 孙伟Contact Name of the ethic committee： Wei Sun伦理委员会联系地址： 中国北京市丰台区南四环西路119号Contact Address of the ethic committee： No. 119, South 4th Ring West Road, Fengtai District, Beijing, China伦理委员会联系人电话： Contact phone of the ethic committee： +86 10 5997 8555 伦理委员会联系人邮箱： Contact email of the ethic committee：研究实施负责（组长）单位： 首都医科大学附属北京天坛医院Primary sponsor： Beijing Tiantan Hospital, Capital Medical University研究实施负责（组长）单位地址： 中国北京市丰台区南四环西路119号Primary sponsor's address： No. 119 South Fourth Ring Road West, Fengtai District, Beijing, China试验主办单位(项目批准或申办者)： Secondary sponsor： 国家： 中国 省(直辖市)： 湖北 市(区县)： Country： China Province： Hubei City： 单位(医院)： 达尔文起点（湖北）生物制药有限责任公司 具体地址： 湖北省武汉东湖新技术开发区九 峰一路 1 号生物创新园二期 A12 栋 1 楼 04 号 Institution hospital： Darwin Origin (Hubei) Biopharmaceutical Co., Ltd. Address： Room 04, 1st Floor, Building A12, Phase II, Biological Innovation Park, No. 1 Jiufeng 1st Road, Wuhan East Lake High-Tech Development Zone, Hubei Province, China经费或物资来源： 自筹Source(s) of funding： Self funding研究疾病： 缺血性脑卒中  Target disease： Ischemic Stroke研究疾病代码：Target disease code：研究类型： 干预性研究Study type： Interventional study研究所处阶段： 其它 Study phase： N/A研究设计： 随机平行对照 Study design： Parallel 研究目的： 观察单次和多次给予不同剂量ALT001对中国健康受试者的安全性； 探索最大耐受剂量(MTD)和后续研究推荐剂量(RD); 探索细胞因子和免疫功能改变。  Objectives of Study： To evaluate the safety of single and multiple doses of ALT001 at various dose levels in healthy Chinese subjects; To explore the maximum tolerated dose (MTD) and the recommended dose (RD) for subsequent studies; To investigate changes in cytokines and immune function.药物成份或治疗方案详述： Description for medicine or protocol of treatment in detail： 纳入标准： 受试者必须符合以下所有标准，才有资格入组本试验： 1. 年龄为18~45周岁(包含临界值，以签署知情同意书时间为准)健康男性或女性 受试者 ； 2. 体重指数(BMI)为18.5~27.9kg/m²(包括临界值),男性受试者体重不得低于 50 kg,女性受试者体重不得低于45kg; 3. 研究者根据受试者的病史、体格检查、生命体征、12导联心电图检查、实验室检 查(血常规、尿常规、血生化、凝血功能)、病毒血清学等结果判断其总体健康状况良好(检查结果正常或异常无临床意义); 4. 女性受试者必须是非怀孕和非哺乳期状态；受试者(男性或女性)同意从筛选期 开始至最后一次使用试验药物后6个月内避孕(采取医学认可的有效避孕措施)； 5. 受试者必须自愿并能够参与研究，签署知情同意书，并承诺完成所有与研究相关的程序和访视，按照试验方案要求完成研究。Inclusion criteria Subjects must meet all of the following criteria to be eligible for enrollment in this trial: 1. Healthy male or female subjects aged 18 to 45 years (inclusive of the upper and lower limits), with age determined by the date of signing the informed consent form; 2. Body Mass Index (BMI) ranging from 18.5 to 27.9 kg/m^2 (inclusive of the upper and lower limits); male subjects must have a body weight of no less than 50 kg and female subjects no less than 45 kg; 3. In good general health as assessed by the investigator based on medical history, physical examination, vital signs, 12-lead electrocardiogram, laboratory tests (complete blood count, urinalysis, blood biochemistry, coagulation function) and viral serology results, with all test findings being either normal or showing clinically insignificant abnormalities; 4. Female subjects must be non-pregnant and non-lactating; all subjects (male and female) must agree to use medically accepted effective contraceptive measures from the screening period until 6 months after the last administration of the investigational product; 5. Subjects must voluntarily agree to and be capable of participating in the study, sign the informed consent form, and commit to completing all study-related procedures and visits in accordance with the requirements of the study protocol.排除标准： 符合以下任一标准的受试者均将从本试验中排除： 1. 过敏性体质(多种药物及食物过敏),有严重过敏/超敏反应史，或经研究者判断 可能会对试验药物或试验药物中的任何成分过敏者(如既往有蛋白类药物过敏史者); 2. 筛选期合并其他严重的和(或)无法控制的重要脏器或不稳定的系统性疾病，包 括但不限于未控制的糖尿病，不稳定型心绞痛，脑血管意外或短暂性脑缺血(筛选前 6个月内),心肌梗塞(筛选前6个月内),严重的充血性心力衰竭，未控制的高血 压，无法控制的活动性感染，肝脏、肾脏或其他严重代谢性疾病，严重胃肠道疾病； 3. 筛选期白细胞或中性粒细胞计数异常且经研究者判定为有临床意义者； 4. 筛选期肝功能异常者：总胆红素>1.5×正常上限(ULN),AST>1.5×ULN,ALT>1.5 ×ULN; 5. 筛选期估算肾小球滤过率<90 mL/min/1.73m²(eGFR公式); 6. 筛选期任何有临床意义的静息心电图的节律、传导或形态异常，以及研究者认为 可能干扰QTc间隔变化的12-导联心电图的任何有临床意义的重要异常，包括ST-T波 形异常，QTc间期>450ms(Fridericia’s校正)或有QTc间期延长综合征家族史； 7. 有出血倾向病史或经确诊的凝血因子异常(如家族性凝血因子缺乏)者； 8. 筛选期休息后生命体征异常，包括收缩压<90mmHg或>139mmHg、舒张压< 60mmHg或>89mmHg、脉搏<50次或>100次/分钟； 9. 筛选前6个月内有过外科手术，或试验期间计划进行手术者； 10. 筛选前6个月内每周饮酒量大于14单位酒精(1单位酒精=360 mL啤酒或45mL 酒精含量为40%的烈酒或150mL葡萄酒)或给药前72小时服用过含酒精的制品，或 酒精呼气测试结果阳性(>0mg/100mL); 11 筛选前3个月内每日吸烟量大于5支或习惯性使用含尼古丁制品(包括但不限于 电子烟、烟斗、雪茄、咀嚼烟草、尼古丁贴片、尼古丁含片或尼古丁口香糖、瓦伦尼 克林、安非他酮),或烟碱筛查阳性者； 12. 筛选期前3个月内献血或失血>400 mL或4周内献血或失血>200 mL或计划在研究 期间献血者； 13. 在筛选前4周内全身使用免疫抑制剂(如皮质类固醇、甲氨蝶呤、硫唑嘌呤、环孢菌素等); 14. 筛选前2周内使用过任何处方药、非处方、中草药或保健品(避孕药物或研究者 评估可以应用的外用药物除外),如半衰期较长，则所需的时间间隔将更长，应至少 为该药物的5个半衰期； 15. 筛选前2周内接受过疫苗接种，或计划在试验期内接种疫苗者； 16. 有药物滥用史的受试者或药物滥用筛查阳性者； 17. 筛选期乙肝(HBV)表面抗原阳性、丙肝(HCV)抗体阳性，人体免疫缺陷病毒 (HIV)抗体阳性，或梅毒螺旋体检测阳性； 18. 不能耐受静脉穿刺者，有晕针晕血史者； 19. 筛选前3个月内参加过其他临床试验，使用了任何其他临床试验用药或器械者； 或既往参与过干细胞疗法或基因疗法治疗； 20. 研究者认为不宜参与本研究的患者(如显著有临床意义的体检或实验室检查异常等)。Exclusion criteria： Subjects who meet any of the following criteria will be excluded from this trial: 1. Having an allergic diathesis (allergic to multiple drugs and foods), a history of severe hypersensitivity/anaphylactic reactions, or being judged by the investigator to be at risk of allergy to the investigational product or any of its components (e.g., a prior history of allergy to protein-based drugs); 2. Complicated with other severe and/or uncontrolled diseases of vital organs or unstable systemic diseases during the screening period, including but not limited to uncontrolled diabetes mellitus, unstable angina pectoris, cerebrovascular accident or transient ischemic attack (within 6 months before screening), myocardial infarction (within 6 months before screening), severe congestive heart failure, uncontrolled hypertension, uncontrollable active infection, severe hepatic, renal or other metabolic diseases, and severe gastrointestinal diseases; 3. Having clinically significant abnormal white blood cell or neutrophil counts during the screening period as determined by the investigator; 4. Having abnormal liver function during the screening period: total bilirubin >1.5×upper limit of normal (ULN), aspartate aminotransferase (AST) >1.5×ULN, alanine aminotransferase (ALT) >1.5×ULN; 5. Having an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73m² (per the eGFR formula) during the screening period; 6. Having any clinically significant abnormal rhythm, conduction or morphology on resting electrocardiogram (ECG) during the screening period, or any clinically significant major ECG abnormalities judged by the investigator to potentially interfere with QTc interval changes, including abnormal ST-T wave morphology, QTc interval >450 ms (per Fridericia’s correction), or a family history of congenital long QT syndrome; 7. Having a history of bleeding tendency or confirmed coagulation factor abnormalities (e.g., congenital coagulation factor deficiency); 8. Having abnormal vital signs after rest during the screening period, including systolic blood pressure <90 mmHg or >139 mmHg, diastolic blood pressure <60 mmHg or >89 mmHg, and pulse rate <50 beats/min or >100 beats/min; 9. Having undergone major surgery within 6 months before screening, or planning to undergo surgery during the trial; 10. Having an alcohol consumption of more than 14 alcohol units per week within 6 months before screening (1 alcohol unit = 360 mL beer, 45 mL spirits [40% alcohol by volume], or 150 mL wine), having consumed alcohol-containing products within 72 hours before drug administration, or having a positive breath alcohol test result (>0 mg/100mL); 11. Having a daily cigarette consumption of more than 5 cigarettes or habitual use of nicotine-containing products (including but not limited to e-cigarettes, pipe tobacco, cigars, chewing tobacco, nicotine patches, lozenges or gum, Varenicline, Bupropion) within 3 months before screening, or having a positive nicotine screening result; 12. Having donated blood or suffered blood loss >400 mL within 3 months before screening, donated blood or suffered blood loss >200 mL within 4 weeks before screening, or planning to donate blood during the trial; 13. Having received systemic immunosuppressants (e.g., corticosteroids, Methotrexate, Azathioprine, Cyclosporine, etc.) within 4 weeks before screening; 14. Having taken any prescription drugs, over-the-counter (OTC) drugs, Chinese herbal medicines or dietary supplements within 2 weeks before screening (except for contraceptives or topical medications approved by the investigator); for drugs with a long half-life, a longer washout period of at least 5 half-lives is required; 15. Having received any vaccination within 2 weeks before screening, or planning to receive vaccination during the trial; 16. Having a history of substance abuse or a positive substance abuse screening result; 17. Testing positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), human immunodeficiency virus antibody (anti-HIV), or Treponema pallidum antibody during the screening period; 18. Having an intolerance to venipuncture, or a history of needle phobia or blood phobia; 19. Having participated in another clinical trial, used any other investigational drugs or medical devices within 3 months before screening, or previously received stem cell therapy or gene therapy; 20. Being deemed ineligible for study participation by the investigator due to other reasons (e.g., significant clinically abnormal physical examination or laboratory test findings).研究实施时间： Study execute time： 从 From 2026-02-12 00:00:00至 To 2026-09-30 00:00:00 征募观察对象时间： Recruiting time： 从 From 2026-02-24 00:00:00 至 To 2026-07-31 00:00:00干预措施： Interventions： 组别： 试验组 样本量： 48 Group： Experimental group Sample size： 干预措施： 单次给药：第1天静脉给予1次 ALT001；多次给药：从第1天开始每日1次，连续静脉给予ALT001，连续给药14天 干预措施代码： Intervention： Single dose: ALT001 will be administered intravenously once on Day 1. Multiple doses: ALT001 will be administered intravenously once daily from Day 1 for 14 consecutive days. Intervention code： 组别： 安慰剂组 样本量： 16 Group： Placebo group Sample size： 干预措施： 单次给药：第1天静脉给予1次安慰剂；多次给药：从第1天开始每日1次，连续静脉给予安慰剂，连续给药14天 干预措施代码： Intervention： Single dose: Placebo will be administered intravenously once on Day 1. Multiple doses: Placebo will be administered intravenously once daily from Day 1 for 14 consecutive days. Intervention code：研究实施地点： Countries of recruitment and research settings： 国家： 中国 省(直辖市)： 北京  市(区县)： Country： China Province： Beijing City： 单位(医院)： 首都医科大学附属北京天坛医院  单位级别： 三甲  Institution hospital： Beijing Tiantan Hospital, Capital Medical University Level of the institution： Tertiary A测量指标： Outcomes： 指标中文名： 不良事件(AE)和严重不良事件(SAE)的发生情况：包括发生次数、类型、严重程度、持续时间、与药物的相关性、与剂量的关系等；因药物毒性停药的受试者比例； 指标类型： 主要指标 Outcome： Occurrence of adverse events (AEs) and serious adverse events (SAEs), including incidence, type, severity, duration, relationship to the study drug, dose relationship, etc.; proportion of subjects who discontinued due to drug toxicity. Type： Primary indicator 测量时间点： 测量方法： Measure time point of outcome： Measure method： 指标中文名： 剂量递增观察期内，各剂量组的显著不耐受事件(SIE)发生率、探索最大耐受剂量 (MTD)、评估后续研究推荐剂量(RD) 指标类型： 主要指标 Outcome： During the dose-escalation observation period: incidence of Significant Intolerance Events (SIE) in each dose cohort; exploration of the Maximum Tolerated Dose (MTD); and evaluation of the Recommended Dose (RD) for subsequent studies. Type： Primary indicator 测量时间点： 测量方法： Measure time point of outcome： Measure method： 指标中文名： 细胞因子(IFN-Y、IL-10、IL-13、IL-1β、IL-4、IL-5、IL-6、GRO-α、TNF-a,IL2) 和免疫功能(IgG、IgM、IgA、CD3+CD4+、CD3+CD8+、CD3+CD4+/CD3+CD8+、CD28+、 CD16+)在用药前后的改变 指标类型： 次要指标 Outcome： Changes in cytokines (IFN-γ, IL-10, IL-13, IL-1β, IL-4, IL-5, IL-6, GRO-α, TNF-α, IL-2) and immune function parameters (IgG, IgM, IgA, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+ ratio, CD28+, CD16+) before and after dosing. Type： Secondary indicator 测量时间点： 测量方法： Measure time point of outcome： Measure method：采集人体标本： Collecting sample(s) from participants： 标本中文名： 血液 组织： Sample Name： Blood Tissue： 人体标本去向 使用后销毁   说明 Fate of sample： Destruction after use Note：征募研究对象情况： Recruiting status： 尚未开始 Not yet recruiting 年龄范围： Participant age： 最小 Min age 18 岁 years 最大 Max age 45 岁 years性别： 男女均可 Gender： Both随机方法（请说明由何人用什么方法产生随机序列）： 统计专家根据“临床研究随机化方案”对试验用药进行随机编码。受试者必须自始至终 处于盲态。 (1)试验采用区组随机方法对筛选成功的受试者进行随机化入组。随机分配编码由 统计分析单位采用SAS 软件的PROC PLAN 过程在计算机上产生随机分配表。试验用的各 类药物将按随机分配表进行编码。 (2)受试者签署知情同意书后，临床试验参加单位给其分配唯一的筛选编号(该编号 不得重复使用),进行筛选相关检查和评价。试验过程中，筛选成功的受试者根据筛选成 功的时间，依次入组并严格按照从小到大的顺序分配随机号，不得跳号(替补受试者除外), 该随机编号为唯一且永久的标识号。Randomization Procedure (please state who generates the random number sequence and by what method)： Biostatisticians shall conduct random coding of the investigational products in accordance with the Randomization Protocol for the Clinical Study. Subjects must remain in a blinded status throughout the trial. (1) The trial adopts the block randomization method for the randomized enrollment of subjects who pass the screening. The random allocation codes shall be generated by the statistical analysis unit via the PROC PLAN procedure of the SAS software on a computer to create a random allocation table. All types of investigational products for the trial shall be coded in accordance with this random allocation table. (2) After a subject signs the informed consent form, the clinical trial site shall assign a unique screening number to the subject (the number shall not be reused), and then conduct screening-related examinations and evaluations. During the trial, subjects who pass the screening shall be enrolled sequentially in the order of their successful screening, and random numbers shall be assigned strictly in ascending numerical order with no skipping of numbers (except for substitute subjects). Such random numbers shall serve as the subjects’ unique and permanent identifiers.是否公开试验完成后的统计结果: Calculated Results after the Study Completed public access: 不公开/Private盲法： 采用双盲设计，除紧急情况及特殊分析需求外，受试者、 研究者、研究中心工作人员、申办者研究团队将对受试者接受的治疗与随机分组信息保持盲态，直至数据库锁定后揭盲。不同剂量组为非盲信息，各剂量组内具体治疗(安慰剂与试验药物)为盲态信息。Blinding： A double-blind design is adopted. Except for emergency situations and special analysis needs, subjects, investigators, study site staff and the sponsor's research team shall remain blinded to the treatment received by subjects and the randomization grouping information until unblinding is performed after database lock. The different dose groups are unblinded information, while the specific treatments (placebo and investigational product) within each dose group are blinded information.是否共享原始数据： IPD sharing 否No共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）： 无The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)： N/A数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC： 电子采集和管理系统Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture： Electronic Data Capture, EDC数据与安全监察委员会： Data and Safety Monitoring Committee： 无/No注册人： Name of Registration： 2026-02-14 11:15:02

本综述概述了用于制备许多现代六元杂环化合物的最常见的合成路线。所报道的例子是基于顶级零售药物分子，结合了来自科学期刊和更广泛的专利文献的合成信息。希望本汇编结合先前发表的关于五元环的综述，为对药物、合成和制备化学感兴趣的个人形成一个全面的基础和参考来源。 The subsections are: 1. Pyridines and quinolines 2. Dihydropyridines and piperidines 3. Pyrimidines and quinazolines 4. Pyrazines and piperazines 5. Pyridazines and perhydropyridazines 6. Triazines and polyazacyclic systems 之前，我们回顾了市面上最畅销的含五元环杂环药物的最常见合成路线，这让我们能够分析药物化学家在过去30年是如何应对挑战的。这项工作不仅是对各种化学转化的概述，也让我们可以判断是否和在何种程度上新的想法和概念已经收获，以提高成功率和加快药物的开发时间。在这篇新的综述文章中，我们希望对目前含有六元杂环的药物的合成路线进行补充汇编。我们相信，芳香族和非芳香族六元结构的结合将提供一个全面的概述，对任何学生、学者或未来对应用化学合成感兴趣的药物化学家都有价值。 clarinex的合成： rosiglitazone的合成路线一： rosiglitazone的合成路线二： pioglitazone的合成： etoricoxib的合成路线一： etoricoxib的合成路线二： moxifloacin的合成： clevidipine的三条合成路线： tiagabine的合成： solifenacin的合成： carmegliptin HCl salt的合成： raltegravir的合成： imatinib的合成路线一： imatinib的合成路线二： erlotinib的合成路线一： erlotinib的合成路线二： lapatinib的合成： varenicline的合成： bortezomib的合成： cilazapril的合成： imiquimod的合成路线一： imiquimod的合成路线二： abacavir的合成： ocinaplon的合成： sidenafil的合成路线一： sidenafil的合成路线二： vardenafil的合成： 参考文献：Beilstein J. Org. Chem. 2013, 9,2265–2319.