Evaluation of XTYW007 in Healthy Subjects and Healthy Subjects With Elevated LDL-C:A Randomized, Double-Blind, Single-Center Phase I/IIa Study of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Food Effect Following Single and Multiple Doses
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Treatment-related adverse events
研究概览
简要总结
Aimed at evaluating the safety, tolerability, and pharmacokinetic characteristics of single and multiple doses of XTYW007 in healthy subjects and healthy subjects with elevated LDL-C, as well as studying the effects of food on the pharmacokinetics and metabolic transformation of XTYW007, and preliminarily assessing the pharmacodynamics of XTYW007.
详细描述
This study is a single-center, randomized, double-blind Phase I/IIa clinical trial assessing the safety, tolerability, and pharmacokinetics of single and multiple doses.Aimed at evaluating the safety, tolerability, and pharmacokinetic characteristics of single and multiple doses of XTYW007 in healthy subjects and healthy subjects with elevated LDL-C, as well as studying the effects of food on the pharmacokinetics and metabolic transformation of XTYW007, and preliminarily assessing the pharmacodynamics of XTYW007.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects voluntarily sign the informed consent before the trial, and fully understand the content, process and possible adverse effects of the trial;
- •They are able to complete the study according to the requirements of the trial protocol;
- •Subjects (including partners) are willing to have no pregnancy plan and voluntarily use effective contraceptive measures within 6 months from screening to the last dose of study drug;
- •Male and female subjects between the ages of 18 and 65 (including borderline values);
- •Male subjects weighing not less than 50 kg and female subjects weighing not less than 45 kg. Body mass index (BMI) = weight (kg)/ height 2 (m2), BMI within the range of 18-28 kg/m2 (including the threshold value);
- •During screening, for single-dose studies, fasting low-density lipoprotein cholesterol (LDL-C): 80 mg/dL < LDL-C < 120 mg/dL (2.06 mmol/L ~ 3.1 mmol/L); for multiple-dose studies, fasting low-density lipoprotein cholesterol (LDL-C) > 110 mg/dL (2.85 mmol/L);
- •Physical examination and vital signs are normal or abnormal without clinical significance.
排除标准
- •Individuals with allergic constitution (allergic to multiple drugs and foods) or intolerance to β-blockers;
- •History of thyroid-related diseases and/or thyroid function abnormalities during the screening phase that are clinically significant;
- •Individuals who smoked more than 5 cigarettes per day in the 3 months prior to the trial;
- •History of drug abuse and/or alcoholism (consuming 14 units of alcohol per week: 1 unit = 285 mL beer, 25 mL spirits, or 100 mL wine);
- •Blood donation or significant blood loss (>450 mL) within 3 months prior to taking the study drug;
- •Use of any prescription drugs, over-the-counter drugs, vitamins, herbal products, or alcohol within 14 days before taking the study drug;
- •Consumption of special foods (such as grapefruit, mango, dragon fruit, grape juice, orange juice, etc., rich in flavonoids or coumarins) within 2 weeks before taking the study drug, or engaging in intense exercise, or other factors affecting drug absorption, distribution, metabolism, or excretion;
- •Significant changes in diet or exercise habits recently;
- •Use of the study drug or participation in a drug clinical trial within 3 months before taking the study drug;
- •Difficulty swallowing or any gastrointestinal diseases affecting drug absorption within 6 months prior to the study;
- •Any disease that increases bleeding risk, such as hemorrhoids, acute gastritis, or gastroduodenal ulcer;
- •Clinically significant ECG abnormalities; QTcF > 470 ms (QTcF = QT/(RR)^0.33);
- •Female subjects who are breastfeeding during the screening or trial phase, planning pregnancy in the near future, or have positive serum pregnancy results;
- •Abnormal clinical laboratory test results with clinical significance, or other clinical findings within 12 months prior to screening that are clinically significant, including but not limited to diseases of the gastrointestinal tract, kidney, liver, nervous system, hematopoietic system, endocrine system, tumors, lungs, immune system, mental health, or cardiovascular and cerebrovascular systems;
- •Any positive result for hepatitis B surface antigen, hepatitis C antibody/core antigen, HIV antigen/antibody, or syphilis treponema antibody during screening;
- •Occurrence of acute illness or concomitant medication use from the screening phase to the start of study medication;
- •Consumption of chocolate, any caffeine-containing or xanthine-containing foods or beverages within 24 hours before taking the study drug;
- •Serum creatinine clearance ≤ 70 mL/min [calculation formula: Ccr: (140 - age) × weight (kg) / (0.818 × Scr) (μmol/L), ×0.85 for females];
- •Subjects with special dietary requirements who cannot consume the complete study meal or who do not agree to adhere to water intake regimen and position restrictions during the trial;
- •Subjects whom the investigator considers to have other factors that make them unsuitable for participation in this trial.
研究组 & 干预措施
Single dose group
Group 1 (0.2 mg), Group 2 (0.6 mg), Group 3 (1.5 mg), Group 4 (3 mg), Group 5, Group A (6 mg), Group 6 (10 mg), Group 7 (15 mg), optional dose Group 8 (20 mg)
干预措施: Test drug XTYW007 capsules and placebo,Single dose group (Drug)
Food Impact Group
Group 5, Subgroup A（6mg）, Group 5, Subgroup B（ 6 mg）
干预措施: Test drug XTYW007 capsules and placebo,Food Impact Group (Drug)
Multiple dosing group
Group 9 (1.5 mg), Group 10 (6 mg), Group 11 (15 mg)
干预措施: Test drug XTYW007 capsules and placebo,Multiple dosing group (Drug)
结局指标
主要结局
Treatment-related adverse events
时间窗: Days 1-11 of administration
Number of participants who experienced treatment-related adverse events as assessed by CTCAE v5.0.
Cmax
时间窗: Days 1-11 of administration
Cmax
Tmax
时间窗: Days 1-11 of administration
Tmax
t1/2
时间窗: Days 1-11 of administration
t1/2
AUC
时间窗: Days 1-11 of administration
AUC
CL/F
时间窗: Days 1-11 of administration
CL/F
Vz/F
时间窗: Days 1-11 of administration
Vz/F
CLr/F
时间窗: Days 1-11 of administration
CLr/F
次要结局
- Ae0-72 h(Days 1-4 of administration)
- Fe0-72 h(Days 1-4 of administration)
- Blood lipids(Days 1-11 of administration)
- Thyroid function(Days 1-11 of administration)
- Sex hormone-binding globulin (SHBG)(Days 1-11 of administration)