A First-in-Human (FIH), Randomized, Double-Blind, Placebo-controlled, Phase 1a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of TU7710 Following Single, Ascending, Intravenous, Dose Administration in Warfarin Anti-coagulated Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Number and proportion of participants with adverse events
研究概览
简要总结
This is a Phase 1a, double-blind, randomized, placebo- controlled, SAD study to assess safety, tolerability, PK, and PD of TU7710 in warfarin treated healthy male participants.
详细描述
The 40 subjects will be divided into 5 cohorts, and the subjects assigned to each cohort will be randomly assigned with 6 persons receiving TU7710 and 2 persons receiving a placebo for TU7710. Each cohort will proceed in sequence and the next cohort study will be decided by the Safety Monitoring Committee (SMC) .
Subjects will be participated in the study after warfarin anti-coagulation to maintain the INR between 2.00 and 3.00 as a preventive measure for potential thrombosis prior to the IP administration.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 19 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age ≥19 and ≤45
- •BMI of ≥18.0 kg/m2 and ≤30.0 kg/m2
- •Body weight of ≥55.0 kg and ≤90.0 kg
- •Provide informed consent and willing to comply with study requirements.
排除标准
- •History or at risk of developing diseases related to venous thromboembolic events or has family history of such disease
- •History of major bleeding/traumatic event or major surgery within 6 month
- •History of any other clinically relevant coagulation disorder (such as gastrointestinal bleeding, hemorrhoid hemorrhage)
- •Abnormal coagulation related laboratory abnormal test results, including protein C, protein S, PT, aPTT
- •history or current symptoms of gastrointestinal, liver, or renal disease that may affect the pharmacokinetics of the IP
- •History of or are currently with hepatitis B or C (active or carrier state) or human immunodeficiency virus (HIV) or syphilis infection.
- •Currently smoking or have smoked within 1 month before IP or positive cotinine results
- •History of alcohol abuse or positive alcohol breath test
- •Excessive caffeine intake within 7 days before IP
- •INR results not between 2.0~3.0 range after warfarin treatment
- •History of hypersensitivity to medicinal product similar to TU7710 active ingredient or excipient
- •Laboratory abnormal test results, such as QTcF <340msec or >450msec (or family history of long QT syndrome), LDL >190mg/dl , Total cholesterol >300mg/dl, triglycerides > 350mg/dl, ALT >1.5*ULN, AST >1.5*ULN, bilirubin >1.5*ULN
- •Abnormal vital sign SBP >140mmHG, DBP <90mmHg, heart rate <40bpm or >85bpm
- •Any medical history that may increase the risk or affect the evaluation of study objectives by participating in this study at the discretion of the investigator. (e.g., neurology or psychiatric history)
研究组 & 干预措施
TU7710
TU7710 of escalating 5 doses
干预措施: TU7710 (Drug)
Normal Saline (placebo of TU7710)
Placebo of TU7710 at corresponding TU7710 dose level
干预措施: Normal saline (Drug)
结局指标
主要结局
Number and proportion of participants with adverse events
时间窗: 30 days post-dose
Number and proportion of participants with adverse events/ adverse reaction /SAE overall and by treatment group
Number of subjects with significant abnormal laboratory values
时间窗: 30 days post-dose
Mean with standard deviation, median, maximum, minimum results of laboratory values in each treatment group. The laboratory parameters that will be assessed are clinical chemistry, hematology and urinalysis.
ADA and Neutralizing antibody results
时间窗: 30 days post-dose
Incidence of subjects with ADA and Nab positive results
Number of subjects with significant abnormal Electrocardiography (ECG) findings
时间窗: 30 days post-dose
Mean with standard deviation, median, maximum, minimum results of ECG results in each treatment group. The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF interval.
Number of subjects With Significant Abnormal vital sign findings
时间窗: 30 days post-dose
Mean with standard deviation, median, maximum, minimum results of vital sign values in each treatment group. The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
次要结局
- Pharmacokinetics assessment_AUC last(4 days post-dose)
- Pharmacodynamic assessment_INR change from baseline(5 days post-dose)
- Pharmacokinetics assessment_Maximum concentration(4 days post-dose)
- Pharmacokinetics assessment_AUC inf(4 days post-dose)
- Pharmacokinetics assessment_Clearance(4 days post-dose)
- Pharmacokinetics assessment_Volume of distribution(4 days post-dose)
- Pharmacokinetics assessment_Dose proportionality(4 days post-dose)
- Pharmacokinetics assessment_Tmax(4 days post-dose)
- Pharmacodynamic assessment_PT change from baseline(5 days post-dose)
- Pharmacodynamic assessment_aPTT change from baseline(5 days post-dose)
- Pharmacokinetics assessment_incremental recovery(4 days post-dose)