Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Single-Ascending Dose Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Subjects With Serious Adverse Event (SAEs) by Treatment Group
研究概览
简要总结
The objective is to evaluate the safety and tolerability of a single-ascending oral dose of UV-4B in healthy subjects and to determine pharmacokinetic parameters describing absorption and elimination following a single dose of UV-4B in healthy subjects.
详细描述
The causative agent of dengue fever is Dengue Virus (DENV), a member of the flavivirus genus. There are four DENV serotypes. Infection with one serotype results in lifelong immunity against that serotype, but only limited short-term cross-protection from infection with the other serotypes. Immunity to one serotype has a downside as subsequent infections by other serotypes increase the risk of developing more severe forms of dengue, which includes the most lethal form of the disease, dengue hemorrhagic fever. Traditional epidemiologic and serologic-based estimates suggest a range of 50 to 100 million DENV infections per year distributed over 100 countries. Recent cartographic-based modeling studies suggest that up to 390 million of dengue infections per year, of which 96 million are associated with clinical symptoms.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects
- •Women: non-pregnant, non-lactating; if of childbearing potential, on specified contraception measures during the study period
- •Men: using barrier contraception measures during the study period
排除标准
- •Health conditions
- •Taking prescription and non-prescription drugs (exceptions: acetaminophen, vitamins, hormonal birth control)
研究组 & 干预措施
Cohort 1 - 3 mg UV-4B
Subjects receiving UV-4B 3 mg oral solution or placebo
干预措施: UV-4B 3 mg (Drug)
Cohort 1 - 3 mg UV-4B
Subjects receiving UV-4B 3 mg oral solution or placebo
干预措施: Placebo (Drug)
Cohort 2 - 10 mg UV-4B
Subjects receiving UV-4B 10 mg oral solution or placebo
干预措施: UV-4B 10 mg (Drug)
Cohort 2 - 10 mg UV-4B
Subjects receiving UV-4B 10 mg oral solution or placebo
干预措施: Placebo (Drug)
Cohort 3- 30 mg UV-4B
Subjects receiving UV-4B 30 mg oral solution or placebo
干预措施: UV-4B 30 mg (Drug)
Cohort 3- 30 mg UV-4B
Subjects receiving UV-4B 30 mg oral solution or placebo
干预措施: Placebo (Drug)
Cohort 4 - 90 mg UV-4B
Subjects receiving UV-4B 90 mg oral solution or placebo
干预措施: UV-4B 90 mg (Drug)
Cohort 4 - 90 mg UV-4B
Subjects receiving UV-4B 90 mg oral solution or placebo
干预措施: Placebo (Drug)
Cohort 5 - 180 mg UV-4B
Subjects receiving UV-4B 180 mg oral solution or placebo
干预措施: UV-4B 180 mg (Drug)
Cohort 5 - 180 mg UV-4B
Subjects receiving UV-4B 180 mg oral solution or placebo
干预措施: Placebo (Drug)
Cohort 6 - 360 mg UV-4B
Subjects receiving UV-4B 360 mg oral solution or placebo
干预措施: UV-4B 360 mg (Drug)
Cohort 6 - 360 mg UV-4B
Subjects receiving UV-4B 360 mg oral solution or placebo
干预措施: Placebo (Drug)
Cohort 7 - 720 mg UV-4B
Subjects receiving UV-4B 720 mg oral solution or placebo
干预措施: UV-4B 720 mg (Drug)
Cohort 7 - 720 mg UV-4B
Subjects receiving UV-4B 720 mg oral solution or placebo
干预措施: Placebo (Drug)
Cohort 8 - 1000 mg UV-4B
Subjects receiving UV-4B 1000 mg oral solution or placebo
干预措施: UV-4B 1000 mg (Drug)
Cohort 8 - 1000 mg UV-4B
Subjects receiving UV-4B 1000 mg oral solution or placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Subjects With Serious Adverse Event (SAEs) by Treatment Group
时间窗: From time of the first dose administration through Day 9 ± 1
Subjects with AEs considered serious by the investigator
Number of Subjects With Vital Sign Values of Toxicity Grade 1 or Higher Postdose by Treatment Group (Safety Population)
时间窗: From time of the first dose administration through Day 9 ± 1
Number of subjects in a treatment group, who had a vital sign value of toxicity Grade 1 or higher: supine and standing systolic blood pressure (BP), supine and standing diastolic BP, supine and standing pulse rate, respiratory rate, and temperature
Number of Subjects With Clinical Laboratory Test Results of Toxicity Grade 1 or Higher at Day 9 by Treatment Group
时间窗: Day 9 ± 1
Number of subjects with Grade 1 toxicity or higher for hematology, coagulation, chemistry and urinalysis analytes. ULN=upper limit of normal; WBC=white blood cell count.
Number of Subjects With Electrocardiogram Outlier Values Postdose by Treatment Group
时间窗: From time of the first dose administration through Day 9 ± 1
Number of subjects in a treatment group with outlier ECG findings: QTcF (Fridericia's), PR, and QRS intervals
Subjects With Treatment-emergent Adverse Event (TEAEs) by Treatment Group
时间窗: From time of the first dose administration through Day 9 ± 1
TEAEs are those AEs occurring only after administration of investigational product
次要结局
- Interval and Cumulative Amount (mg) of UV-4 Excreted in Urine, Ae, by Treatment Group(Pooled urine samples were collected at predose (-12 to 0 hour), and from 0 to 6, 6 to 12, 12 to 24, and 24 to 48 hours postdose)
- Cmax by Treatment Group: UV-4(Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose))
- Tmax by Treatment Group: UV-4(Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose))
- Vz/F by Treatment Group: UV-4(Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose))
- CLr by Treatment Group: UV-4(Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose))
- AUC(0-last) by Treatment Group: UV-4(Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose))
- AUC(0-inf) by Treatment Group: UV-4(Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose))
- CL/F by Treatment Group: UV-4(Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose))
- Interval and Cumulative Percent of UV-4 Excreted in Urine, fe, by Treatment Group(Pooled urine samples were collected at predose (-12 to 0 hour), and from 0 to 6, 6 to 12, 12 to 24, and 24 to 48 hours postdose)
- t(1/2) by Treatment Group: UV-4(Blood samples were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 18, 24, 36, and 48 hours postdose (1 hour window for predose))