NCT06385964已完成1 期
A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Dose of SHR-4597 Inhalation in Healthy Subjects and Asthmatic Patients
Guangdong Hengrui Pharmaceutical Co., Ltd1 个研究点 分布在 1 个国家目标入组 62 人开始时间: 2024年5月7日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Incidence and severity of inhalant adverse events after 4 days of single inhalation of SHR4597 in healthy subjects
研究概览
简要总结
The primary objective of this randomized, double-blind, single/multiple ascending dose, placebo-controlled Phase I clinical trial was to evaluate the safety and tolerability of SHR-4597 in healthy subjects and asthmatic patients. The study consists of two parts: Part 1 involves single ascending inhalation dose in healthy subjects; Part 2 involves multiple ascending inhalation dose in asthmatic patients, further divided into Part 2A: multiple ascending inhalation dose in mild to moderate asthmatic patients, and Part 2B: multiple ascending inhalation dose in moderate to severe asthmatic patients. Subsequent lung pharmacokinetic studies of SHR-4597 inhalation will be conducted based on patients' PKPD data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects:
- •Understand the specific procedures of the trial, voluntarily participate in this trial, and sign the informed consent form in writing.
- •Aged between 18 and 55 years old (inclusive of boundary values).
- •Male subjects with a weight of ≥ 50 kg and female subjects with a weight of ≥ 45 kg, with a body mass index (BMI) between 18 and 30 kg/m2 (inclusive of boundary values).
- •Vital signs, physical examinations, laboratory tests, chest X-rays, etc., are either normal or clinically insignificant in abnormalities.
- •Female subjects of reproductive potential or male subjects whose partners are of reproductive potential must agree, from the time of signing the informed consent form until 1 month after the last dose of study drug administration, to have no plans for pregnancy and voluntarily adopt effective contraception measures (including partners), while also avoiding sperm/egg donation (see Appendix 1 for details).
- •During the study period, participants must be able to comply with all study regulations and procedures and be able to use the inhalation device used in this study correctly.
- •Asthma patients:
- •Age ≥ 18 years and ≤ 75 years, gender not specified.
- •Body Mass Index (BMI) during screening period ≥ 18 and ≤ 30 kg/m
- •History records and objective evidence of asthma diagnosis meeting current guidelines in the 12 months prior to randomization.
- •Not received any asthma treatment or only used short-acting bronchodilators (SABA) on an as-needed basis in the 4 weeks prior to randomization; or received maintenance therapy with medium to high daily doses of inhaled corticosteroids (ICS) and/or other asthma control medications for at least 3 months prior to randomization, and the dosage regimen and asthma condition remained stable in the 4 weeks prior to randomization.
- •FEV1 ≥ 60% or ≥40% and < 80% of predicted value before inhalation bronchodilator use during screening and baseline.
- •FeNO value ≥ 25 ppb during screening and baseline.
- •Female subjects of reproductive potential or male subjects whose partners are of reproductive potential must agree, from the time of signing the informed consent form until 1 month after the last dose of study drug administration, to have no plans for pregnancy and voluntarily adopt effective contraception measures (including partners), while also avoiding sperm/egg donation (see Appendix 1 for details).
- •Voluntarily sign the informed consent form to participate in this study.
排除标准
- •Healthy subjects:
- •Suffering from any clinically serious disease such as circulatory, endocrine, nervous, digestive, respiratory, hematological, immunological, psychiatric and metabolic abnormalities, or any other disease that might interfere with the study results;
- •Previous history of malignant tumor;
- •Current or recent (within 3 months) respiratory disease or a history of severe respiratory disease, and researchers assess that it may affect drug absorption or pose a safety risk;
- •Patients with severe infection, severe trauma or major surgical operation within 3 months before administration; Patients who plan to undergo surgery during the trial period and within two weeks of its end;
- •12-lead ECG abnormalities are clinically significant or ECG QT interval (QTc) > 450 ms in male subjects and ECG QTc > 470 ms in female subjects;
- •Screening for infectious diseases during the screening period, including positive results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody, human immunodeficiency virus antibody, and syphilis treponema antibody;
- •People with a suspected history of allergy to the investigational drug or any of the ingredients in the investigational drug, allergies or a history of severe drug allergy;
- •Previous blood collection difficulties or can not tolerate venipuncture, such as fainting needle, fainting blood
- •Had taken any prescription, over-the-counter, or Chinese herbal medicine within 14 days prior to taking the study drug, or within 5 half-lives of the drug at the time of screening; Plan to take non-study medications during the trial period.;
- •Participants who have participated in clinical trials of any drug or medical device within 3 months prior to screening, or those still within 5 half-lives of a drug prior to screening (whichever is longer);
- •Blood donation or blood loss ≥ 200 mL within 1 month prior to administration, or blood donation or blood loss ≥ 400 mL within 3 months prior to administration, or received blood transfusion within 8 weeks;
- •Average smoking ≥ 5 cigarettes per day in the three months prior to administration; More than 15 g of alcohol per day on average in the month prior to administration (15 g of alcohol is equivalent to 450 mL of beer or 150 mL of wine or 50 mL of low-alcohol liquor);
- •People who do not refrain from smoking, drinking or consuming caffeinated food or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before administration and during the trial period; Those who cannot prohibit the consumption of grapefruit or grapefruit juice; And those who have special requirements for diet and cannot comply with a unified diet;
- •Subjects who are pregnant (tested positive during screening or baseline pregnancy test) or who plan to become pregnant while breastfeeding or during the study;
- •Participants with positive drug screening or alcohol breath test during screening visit/baseline visit;
- •Other conditions deemed by the investigator as unsuitable for participation in this trial;
- •Asthma patients:
- •Combined with clinically significant lung diseases, including but not limited to active pulmonary tuberculosis, bronchiectasis, atelectasis, idiopathic pulmonary fibrosis, bronchopulmonary aspergillosis, and chronic obstructive pulmonary disease (COPD);
- •Malignant tumors diagnosed within 5 years prior to randomization (Excluding malignancies with low risk of metastasis and death, such as adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix);
- •Combined with poorly controlled hypertension (systolic blood pressure ≥180mmHg, and/or diastolic blood pressure ≥110mmHg during screening) or uncontrolled severe cardiovascular and cerebrovascular disease;
- •Known immunodeficiency;
- •A history of infections requiring clinical intervention within 4 weeks prior to randomization, including but not limited to respiratory infections:
- •Known parasitic infection within 6 months prior to randomization;
- •Receiving a non-selective beta-blocker (e.g., propranolol) within 1 week prior to randomization;
- •Blood donation or significant blood loss (≥400ml), or transfusion of blood products or immunoglobulin within 4 weeks prior to randomization;
- •Received attenuated live vaccines within 4 weeks prior to randomization;
- •Allergen immunotherapy was administered 8 weeks before randomization
- •Used systemic immunosuppressive agents (including systemic corticosteroids for asthma treatment, and other systemic corticosteroids <3 days for conditions other than asthma), or immunomodulators, or biologics or Th2 cell cytokine inhibitors within 12 weeks prior to randomization or within 5 half-lives of the drug (whichever is longer, with reference to the drug's prescribing information; for drugs with unknown half-life, the 12 weeks prior to randomization is considered;
- •Bronchial thermoplasty was performed within 1 year prior to randomization
- •Planned surgical procedures during the study period, or other therapeutic measures deemed by the investigator to potentially affect the assessment of the subjects;
- •The screening period or baseline laboratory tests showed significant abnormalities
- •Prolonged ECG QTc interval (men >450ms, women >470ms) or other clinically significant abnormal results that may pose a significant safety risk to subjects during the screening period
- •Screening period is still smoking or quit smoking less than 6 months, or previous smoking ≥10 pack years (pack years = number of years of smoking × number of packs per day)
- •A history of drug use, alcohol abuse (average consumption of ≥14 units of alcohol per week: 1 unit = 285 mL for beer, or 25 mL for spirits, or 100 ml for wine) or drug abuse within 1 year prior to screening
- •Participated in another clinical study and used investigational drugs containing active ingredients within 30 days prior to screening, or still within 5 half-lives of the investigational drug at the time of screening (whichever is longer).
- •Subjects who are pregnant (screening or baseline blood pregnancy test positive) or who plan to become pregnant while breastfeeding or during the study
- •People who are allergic to the drug or its excipients, allergic or have a history of severe drug allergy
- •Other reasons deemed by the investigator as unsuitable for participation in the study
研究组 & 干预措施
SHR-4597
Experimental
干预措施: SHR-4597 (Drug)
SHR-4597 Placebo
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and severity of inhalant adverse events after 4 days of single inhalation of SHR4597 in healthy subjects
时间窗: 4 days for healthy subjects
Incidence and severity of inhalant adverse events after 16 days of multiple inhalation of SHR4597 in asthmatic patients,
时间窗: 16 days for asthmatic patients.
次要结局
未报告次要终点
研究者
研究点 (1)
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