A Single-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Oral Doses of RFUS-949 Tablets in Healthy Chinese Participants
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events (AEs) and serious adverse events (SAEs).
研究概览
简要总结
This is a single-center, randomized, double-blind, placebo-controlled Phase I clinical trial. The primary objective is to evaluate the safety, tolerability, and pharmacokinetics (PK) of RFUS-949 tablets following multiple oral doses in healthy Chinese adult participants (aged 18 to 45 years).
The study is designed to explore the multiple-dose characteristics of the investigational drug. It consists of a once-daily (QD) dosing cohort and three twice-daily (BID) dose escalation cohorts. Participants will receive multiple oral doses of either RFUS-949 or a matching placebo in a fasting state for 6 consecutive days, with rigorous safety monitoring and PK blood sampling throughout the study period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent form (ICF) prior to the study, fully understands the study content, procedures, and possible adverse reactions; willing to participate and able to complete the study according to the protocol requirements.
- •Male or female, aged 18 to 45 years (inclusive).
- •Body weight >= 50.0 kg for males and >= 45.0 kg for females, with Body Mass Index (BMI) between 19.0 and 28.0 kg/m^2 (inclusive).
- •Female participants and their partners are willing to have no pregnancy plans and use effective contraception methods from 2 weeks prior to screening up to 6 months after the last dose; male participants and their partners are willing to have no pregnancy plans and use effective contraception methods from signing the ICF up to 6 months after the last dose. No sperm or egg donation plans during this period.
排除标准
- •Known allergy to the active ingredient or excipients of the study drug, history of specific allergies (e.g., asthma, urticaria, eczema), or highly allergic constitution (e.g., allergic to two or more drugs/foods, highly sensitive to environmental substances).
- •History or presence of clinically significant diseases requiring exclusion as judged by the investigator, including but not limited to neurological/psychiatric, respiratory, cardiovascular, hematological/lymphatic, urinary, endocrine, immune system diseases, and metabolic abnormalities.
- •History of dysphagia or gastrointestinal diseases, especially those affecting drug absorption (e.g., gastric or small bowel resection, gastric or duodenal ulcers, atrophic gastritis, gastrointestinal bleeding, obstruction, cholecystitis, gallstones), or chronic constipation/diarrhea.
- •Received surgical operation within 3 months prior to randomization, planned surgery during the study, or previous surgery that may affect drug absorption, distribution, metabolism, or excretion.
- •Clinically significant abnormal findings in physical examination, vital signs, or laboratory tests at screening, which in the opinion of the investigator make the participant unsuitable for the study.
- •* History or presence of prolonged QTc interval, or screening QTcF > 450 ms (females) or QTcF > 430 ms (males) (Fridericia's formula: QTc = QT/RR^0.33), or clinically significant abnormal ECG results at screening.
- •Positive test results for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, Treponema pallidum (syphilis) antibody, or Human Immunodeficiency Virus (HIV) antibody at screening.
- •Use of any prescription drugs, over-the-counter (OTC) drugs, herbal medicines, vitamins, or dietary supplements within 14 days or 5 half-lives of the drug/active metabolite (whichever is longer) prior to randomization.
- •Use of any drugs that inhibit or induce hepatic drug metabolism within 30 days prior to randomization (e.g., inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; inhibitors: SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines, statins).
- •Consumption of dragon fruit, mango, grapefruit, starfruit, or foods/drinks prepared from them, or foods/drinks containing xanthine, caffeine, or alcohol (including chocolate, tea, coffee, cola, cocoa, etc.), or other special diets affecting drug absorption, distribution, metabolism, or excretion within 48 hours prior to randomization, or inability to stop such diet during the study.
- •Average daily consumption of excessive tea, coffee, and/or caffeinated beverages (> 8 cups/day, 1 cup ≈ 250 mL) within 3 months prior to randomization, or inability to abstain during the study.
- •Special dietary requirements or inability to accept the standardized diet during the study.
- •Intolerance to venipuncture, or history of needle phobia or blood phobia.
- •Smoking more than 5 cigarettes per day within 3 months prior to randomization, or inability to stop using any tobacco products during the study.
- •Average weekly alcohol consumption > 14 units (1 unit ≈ 360 mL beer, 45 mL spirits with 40% alcohol, or 150 mL wine) within 3 months prior to randomization, inability to abstain from alcohol during the study, or a positive alcohol breath test.
- •History of drug abuse within 6 months prior to randomization, positive result in any drug abuse screen, or history of drug addiction/long-term drug use.
- •Vaccinated within 1 month prior to randomization or plan to be vaccinated during the study.
- •Blood donation or blood loss >= 200 mL, or receipt of blood transfusion/blood products within 3 months prior to randomization, or plan to donate blood or blood components during the study or within 3 months after the study ends.
- •Female participants who are pregnant, lactating, or have a positive pregnancy test result at screening or during the study.
- •Female participants who have used oral contraceptives within 30 days, or long-acting estrogen or progestin injections/implants within 6 months prior to study drug administration.
- •Participation in another clinical trial and received study treatment within 3 months prior to randomization.
- •Any other condition that, in the opinion of the investigator, makes the participant unsuitable for the study.
结局指标
主要结局
Number of participants with adverse events (AEs) and serious adverse events (SAEs).
时间窗: From screening (Day -14) up to telephone follow-up at Day 13 (±1).
Safety and tolerability will be assessed by monitoring the incidence and severity of AEs/SAEs, physical examinations, clinical laboratory tests (hematology, blood biochemistry, coagulation, urinalysis), vital signs, and 12-lead ECGs.
Maximum plasma concentration (Cmax) of RFUS-949.
时间窗: Up to Day 9 (72 hours after the last dose on Day 6).
Cmax will be evaluated after the first dose, and steady-state Cmax (Cmax,ss) will be evaluated after the last dose.
Area under the plasma concentration-time curve (AUC) of RFUS-949.
时间窗: Up to Day 9 (72 hours after the last dose on Day 6).
AUC from time zero to the last quantifiable concentration (AUC0-t) will be evaluated after the first dose, and steady-state AUC within the dosing interval (AUC0-tau,ss) will be evaluated after the last dose.
次要结局
未报告次要终点
研究者
Cao Yu
Professor
The Affiliated Hospital of Qingdao University