A Randomized, Double-Blind, Parallel Placebo-Controlled, Single and Multiple Ascending Dose Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Characteristics of Oral DC6001 Tablet in Healthy Chinese Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
This study adopts a randomized, double-blind, parallel placebo-controlled dose-escalation design, consisting of two parts: Part 1 includes a single ascending dose (SAD) study plus a food effect (FE) study, and Part 2 is a multiple ascending dose (MAD) study.
详细描述
Part 1: SAD and FE Studies The SAD and FE studies are conducted concurrently, with a total of 5 dose groups: 2 mg, 5 mg, 10 mg, 20 mg, and 40 mg. A total of 46 healthy adult subjects are planned for enrollment. Except for the 5 mg group, each dose group will include 8 subjects, who will be randomly assigned to receive DC6001 tablets (6 subjects) or DC6001 placebo (2 subjects). The 5 mg group will be combined with the FE study, with 14 planned subjects randomly allocated to DC6001 tablets (12 subjects) or placebo (2 subjects). In the first cycle, a single dose will be administered under fasting conditions. After blood sample collection and safety assessment on Day 9 (D9), the second cycle will be conducted on Day 10 (D10) with administration under high-fat postprandial conditions, followed by blood sample collection and discharge safety examinations.
Part 2: MAD Study The MAD study is tentatively designed with 3 dose groups: 2 mg, 5 mg, and 10 mg (to be adjusted based on SAD study results). A total of 30 healthy adult subjects are planned for enrollment, with 10 subjects per dose group randomly assigned to receive DC6001 tablets (8 subjects) or DC6001 placebo (2 subjects). The tentative administration regimen is once-daily fasting administration for 14 consecutive days (to be adjusted based on SAD study results).
The SAD and MAD study will proceed sequentially from the lowest dose group. After subjects in a given dose group complete discharge safety examinations, the Safety Review Committee (SRC) will assess whether the dose escalation termination criteria are met. If not, the dose will be escalated to the next group until the highest dose group is completed.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers aged 18-55 years (inclusive) at the time of signing the informed consent form, regardless of gender;
- •Male subjects with a body weight ≥ 50.0 kg and female subjects with a body weight ≥ 45.0 kg; BMI ranging from 19.0 to 28.0 kg/m² (inclusive of critical values);
- •Women of childbearing potential (WOCBP) or male subjects must agree to have no childbearing plans and voluntarily adopt effective contraceptive measures for 6 months from pre-screening to the last administration of the study drug, with no plans for sperm or egg donation. For WOCBP: The serum pregnancy test result of WOCBP must be negative before the first administration;
- •No history of major diseases; physical examination, vital signs, 12-lead electrocardiogram (ECG), chest X-ray, and laboratory test results during screening are normal, or slightly exceed the normal reference range but are deemed clinically insignificant by the investigator;
- •Subjects are able to maintain good communication with the investigator, comply with all requirements of the clinical trial, and voluntarily sign the informed consent form.
排除标准
- •Subjects with clinically significant abnormalities or diseases occurring within 1 week prior to screening or currently present that require exclusion;
- •Subjects with digestive system diseases affecting the absorption of fat-soluble vitamins occurring within 3 months prior to screening or currently present;
- •Subjects with diseases related to vitamin A deficiency occurring within 3 months prior to screening or currently present;
- •Subjects with acute diseases occurring from the screening phase to the first administration of the study drug that, in the investigator's judgment, may affect the study results;
- •History of severe visual, ocular, or retinal diseases;
- •Subjects with dysphagia;
- •Subjects with known or suspected allergic reactions to the study drug or any of its excipients (as judged by the investigator); or subjects with clinically significant atopy or history of allergic diseases (as judged by the investigator);
- •Subjects who have undergone surgery within 3 months prior to screening that, in the investigator's judgment, may affect drug absorption, distribution, metabolism, or excretion, or have severe surgical sequelae; or subjects planning to undergo surgery during the study;
- •Subjects who have donated blood, lost a large amount of blood (≥ 400 mL), donated ≥ 2 units of component blood, or received blood transfusion within 3 months prior to the first administration of the study drug; or subjects planning to donate blood during the study;
- •Subjects who have received any investigational drug or participated in any interventional clinical study within 3 months prior to the first administration of the study drug;
- •Subjects who smoked an average of more than 5 cigarettes per day within 3 months prior to the first administration of the study drug, or cannot abstain from using any tobacco products during the study;
- •Subjects who consumed an average of more than 14 units of alcohol per week within 3 months prior to the first administration of the study drug, or cannot abstain from using any alcohol-containing products during the study; or subjects with a positive breath alcohol test prior to study drug administration;
- •Subjects who consumed excessive tea, coffee, and/or caffeinated beverages within 3 months prior to the first administration of the study drug, or cannot abstain from consuming tea, coffee, and/or caffeinated beverages during the study;
- •Subjects who used any prescription drugs, over-the-counter drugs, Chinese patent medicines, Chinese herbal medicines, vitamins, or health food products within 28 days prior to screening or within 5 drug half-lives (whichever is shorter);
- •Subjects whose 12-lead electrocardiogram (ECG) during the screening period meets any of the following criteria: 1) PR interval > 200 ms; 2) QTcF > 450 ms; 3) QRS duration > 110 ms; 4) QT interval > 500 ms; 5) Heart rate (HR) < 50 bpm;
- •Pregnant or lactating female subjects; or female subjects of childbearing potential (WOCBP) with a positive serum pregnancy test at any time prior to the first administration;
- •Subjects with positive results or results exceeding the upper limit of the reference range in the eight infectious and immunological tests, which are deemed clinically significant by the investigator: hepatitis B virus (HBV) serology, hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV)-P24 antigen/antibody, and syphilis-specific antibody;
- •Subjects with a positive urine drug screen or a history of drug abuse or drug use within 5 years prior to the study;
- •Subjects who consumed or drank pitaya, mango, grapefruit, carambola, or foods/beverages prepared from these fruits; or foods/beverages containing xanthine, caffeine, or alcohol; or other special diets that may affect drug absorption, distribution, metabolism, or excretion within 72 hours prior to the first administration;
- •Subjects with special dietary requirements, lactose intolerance, or inability to accept a unified diet;
- •Subjects deemed unsuitable for participation in the study by the investigator.
研究组 & 干预措施
SAD: DC6001
Participants received single dose of DC6001 orally. Dose levels are 2 mg, 5 mg, 10 mg, 20 mg and 40 mg.
干预措施: DC6001 (Drug)
SAD: Placebo
Participants received single dose of placebo orally.
干预措施: Placebo (Drug)
MAD: DC6001
Participant received DC6001 orally once daily for 14 days. Dose levels are 2 mg, 5 mg and 10 mg.
干预措施: DC6001 (Drug)
MAD: Placebo
Participant received DC6001 placebo matching DC6001 orally once daily for 14 days.
干预措施: Placebo (Drug)
FE: DC6001
Participants received single dose of DC6001 5 mg orally under fed conditions.
干预措施: DC6001 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Up to 28 days
Incidence and severity of adverse events as assessed by CTCAE Version 6.0
次要结局
- The area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-∞)(Time Frame: From time zero up to 192 hours post-dose)
- The time required for the plasma concentration to decrease by half (T1/2)(From time zero up to 192 hours post-dose)
- Change from baseline in plasma RBP4 levels(From time zero up to 336 hours post-dose)
- The maximum plasma concentration of the drug (Cmax)(From time zero up to 192 hours post-dose)
- The time at which the peak plasma concentration is reached (Tmax)(From time zero up to 192 hours post-dose)
- The area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t)(From time zero up to 192 hours post-dose)