A Phase I, Randomized, Double-blind, Placebo-Controlled, Single Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous SHR0410 in Healthy Male Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Incidence of Adverse events in terms of changes in Physical examinations
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, single ascending-dose study to investigate the effect of a single intravenous (IV) dose of SHR0410 at 6 dose levels (0.5 μg/kg, 1 μg/kg, 2 μg/kg, 5 μg/kg, 10 μg/kg and 20 μg/kg) in healthy participants.
详细描述
Forty eight eligible participants will be enrolled into the 6 dose cohorts. For each cohort, a sentinel group of 2 subjects (1 receiving SHR0410 and 1 receiving placebo) will be dosed first (1:1 ratio). If no drug related adverse events occur in the sentinel participants, the remaining 6 subjects in a cohort will be dosed on the next day or later in a 5:1 ratio (5 subjects receiving SHR0410 and 1 subject receiving placebo). SHR0410 will be diluted in saline and administered as a 15 min constant dose IV infusion at a rate of 20 ml/hr on Day 1.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male between the ages of 18 and 45 years, inclusive.
- •Body mass index (BMI) of 18.0 to 30.0 kg/m2 and a total body weight of 50 kg to 125kg, inclusive.
- •Considered generally healthy upon completion of medical history, physical examination, vital signs, SpO2, laboratory parameters, and ECG, as judged by the Investigator.
排除标准
- •Known sensitivity to any of the components of the investigational product formulation, or any other opioids.
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- •Any other medical or psychological condition, which in the opinion of the Investigator, might create undue risk to the participant or interfere with the participant's ability to comply with the protocol requirements, or to complete the study.
研究组 & 干预措施
0.5 μg/kg SHR0410
8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 0.5μg/kg SHR0410 (n=6) or placebo (n=2)
干预措施: 0.5μg/kg SHR0410 (Drug)
1 μg/kg SHR0410
8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 1μg/kg SHR0410 (n=6) or placebo (n=2)
干预措施: 1μg/kg SHR0410 (Drug)
2 μg/kg SHR0410
8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 2μg/kg SHR0410 (n=6) or placebo (n=2)
干预措施: 2μg/kg SHR0410 (Drug)
5 μg/kg SHR0410
8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 5μg/kg SHR0410 (n=6) or placebo (n=2)
干预措施: 5μg/kg SHR0410 (Drug)
10 μg/kg SHR0410
8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 10μg/kg SHR0410 (n=6) or placebo (n=2)
干预措施: 10μg/kg SHR0410 (Drug)
20 μg/kg SHR0410
8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 10μg/kg SHR0410 (n=6) or placebo (n=2)
干预措施: 20μg/kg SHR0410 (Drug)
结局指标
主要结局
Incidence of Adverse events in terms of changes in Physical examinations
时间窗: Up to Day 8
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 8
Oral temperature, respiratory rate, blood pressure, and pulse rate
Incidence of Adverse events in terms of changes in Hematology
时间窗: Up to Day 8
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 8
Urobilinogen Dipstick urinalysis, including: pH, Specific gravity, Protein, Blood, Leukocytes, Glucose, Ketones, Bilirubin, Nitrites
Incidence of Adverse events in terms of changes in Biochemistry (fasting)
时间窗: Up to Day 8
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 12-lead ECGs
时间窗: Up to Day 8
The 12-lead ECGs must be recorded after the subjects have rested in the supine position for 5 minutes to ensure a stable baseline.
次要结局
- Area under the plasma concentration versus time curve (AUC)(Up to 24 hours post dose)
- Time to the peak plasma concentration (Tmax)(Up to 24 hours post dose)
- Urine output rate(Up to 48 hours post dose)
- Peak Plasma Concentration (Cmax)(Up to 24 hours post dose)
- Half-time (T1/2)(Up to 24 hours post dose)
- Serum prolactin release rate(Up to 48 hours post dose)