A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of SHR4640 in Male Subjects With High Serum Uric Acid Level
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of Adverse events in terms of changes in Biochemistry (fasting)
研究概览
简要总结
This is a single-Center, randomized, double-Blind, placebo-controlled, multiple ascending-dose Phase I trail.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male, aged between 18 and 65 years, inclusive.
- •Body weight ≥ 50 kg and body mass index between 18.0 and 35.0 kg/m2, inclusive.
- •Screening sUA level ≥0.36 mmol/L.
- •Considered generally healthy upon completion of medical history, full physical examination, vital signs, laboratory parameters (including thyroid function and serological tests, hematology, urinalysis, and biochemistry), 12-lead ECG, and abdominal ultrasound, as judged by the Investigator.
- •Agrees to use a highly effective method of contraception, i.e. condom and suitable contraception for his female partner e.g. oral contraceptive or intrauterine contraceptive device during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence throughout the study period and for 30 days following final dose of study drug, and must agree to refrain from sperm donation from Day -2 until at least 30 days following final dose of study drug.
- •Negative drug screen (including alcohol) at screening and on admission to clinical site.
- •Able to understand the study procedures and the risks involved and must be willing to provide a written informed consent before any study-related activity.
排除标准
- •History of hypersensitivity to SHR4640 or its analogues.
- •History of gout.
- •Screening alanine aminotransferase, aspartate aminotransferase, total bilirubin, or gamma glutamyl transferase > 1.5 × upper limit of normal.
- •Positive result for human immunodeficiency virus (HIV).
- •Positive result for hepatitis B surface antigen or hepatitis C virus antibody.
- •History or presence of kidney stones.
- •Acute or chronic illness that, in the opinion of the Investigator, might confound the results of the trial or pose risk to the subject when administering the trial product.
- •Undergone major surgery within 3 months of Day 1 or has surgery planned during study participation.
- •Donated any blood or plasma in the past month or more than 400 mL within 3 months of Day
- •Has unsuitable venous for blood sampling.
- •Use of tobacco products within 30 days of Day
- •Heavy caffeine drinker (more than 5 cups or glasses of caffeinated beverages per day).
- •History of drug and/or alcohol abuse in the last year.
- •Consumes more than 14 units of alcohol per week (1 unit = 250 mL beer, 25 mL of 40% spirits and 125 mL glass of wine).
- •Consumes grapefruit and/or poppy seed within 5 days of Day
- •Unable to refrain from strenuous exercises, tobacco products, alcohol, grapefruit, and/or poppy seed from Day -2 to Day
- •Use of any of the following, unless agreed as nonclinically relevant by the Investigator and the Sponsor:
- •Prescription medication within 2 weeks of Day
- •Over-the-counter medication within 1 week of Day
- •Use of any over the-counter, nutraceuticals, or prescription medications that might interfere with the absorption, distribution, metabolism, or excretion of SHR4640 (proton-pump inhibitor, fluconazole, indomethacin, ranitidine, flurbiprofen, probenecid, aprepitant, etc.) within 1 month of Day
- •Received the last dose of a study drug (or treatment with a medical device) within 30 days or 5 T1/2 (whichever is longer) of the study drug of Day 1 or are currently participating in another study of a study drug (or medical device).
- •Any other medical or psychological condition, which in the opinion of the Investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or to complete the study.
研究组 & 干预措施
SHR4640 2.5mg
6 subjects assigned to 2.5mg SHR4640 and 2 subjects assigned to placebo
干预措施: SHR4640 (Drug)
SHR4640 10mg
6 subjects assigned to 10mg SHR4640 and 2 subjects assigned to placebo
干预措施: SHR4640 (Drug)
SHR4640 20mg
6 subjects assigned to 20mg SHR4640 and 2 subjects assigned to placebo
干预措施: SHR4640 (Drug)
结局指标
主要结局
Incidence of Adverse events in terms of changes in Biochemistry (fasting)
时间窗: Up to Day 14
Including Serum creatinine, Urea, Alanine aminotransferase, Aspartate aminotransferase, Gamma glutamyl transferase, Total bilirubin, Total protein, Albumin, Alkaline phosphatase, Serum uric acid, Glucose, Triglycerides, Total cholesterol, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol
Incidence of Adverse events in terms of changes in Physical examinations
时间窗: Up to Day 14
Review of body weight and height; general appearance; head; eyes; ears/nose/throat; neck; lymph nodes; neurological and musculoskeletal systems; heart; lungs; abdomen; skin; and extremities
Incidence of Adverse events in terms of changes in Vital signs
时间窗: Up to Day 14
Oral temperature, respiratory rate, blood pressure, and pulse rate
Incidence of Adverse events in terms of changes in 12-lead ECGs
时间窗: Up to Day 14
The 12-lead ECGs must be recorded after the subjects have rested in the supine position for 5 minutes to ensure a stable baseline.
Incidence of Adverse events in terms of changes in Hematology
时间窗: Up to Day 14
Hemoglobin Hematocrit Erythrocytes count Mean cell volume, Mean cell hemoglobin concentration, Leukocytes count, Neutrophils count, Lymphocytes count, Monocytes count, Eosinophils count, Basophils count, Platelets count
Incidence of Adverse events in terms of changes in Urinalysis
时间窗: Up to Day 14
Urobilinogen Dipstick urinalysis, including: pH, Specific gravity, Protein, Blood, Leukocytes, Glucose, Ketones, Bilirubin, Nitrites
次要结局
- Peak Plasma Concentration (Cmax) (of single dose and at stable status)(Up to Day 10)
- Area under the plasma concentration versus time curve (AUC) (of single dose and at stable status)(Up to Day 10)
- Half-time (T1/2) (of single dose and at stable status)(Up to Day 10)
- Time to the peak plasma concentration (Tmax) (of single dose and at stable status)(Up to Day 10)
- Changes in serum uric acid concentration from baseline(Up to Day 10)
- Changes in urinary uric acid excretion from baseline(Up to Day 10)