A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Group, Single Ascending Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Ziresovir in Healthy Subjects
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
- change from baseline in pH from urinalysis
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and pharmacokinetics (PK) of ziresovir following a single ascending oral dose administration in healthy adult subjects under fasted conditions.
详细描述
Up to 3 dose cohorts are planned. The ziresovir dose level of each cohort is determined based on the collective clinical and nonclinical data of ziresovir.
The proposed dose levels of Cohorts 1, 2 and 3 are 300 mg and up to 600 mg and up to 900 mg, respectively.
A total of up to 24 subjects will be randomized with 18 subjects to receive active drug and 6 subjects to receive placebo in a double-blind fashion. Eight subjects will be randomized in each dose cohort, with 6 subjects to receive active drug and 2 subjects o receive placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Capable of giving written informed consent and complying with study procedures;
- •Between the ages of 18 and 55 years, inclusive;
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50 kg;
- •Female subjects must have a negative pregnancy test result at screening;
- •Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, 12-lead ECG, and vital signs;
- •Willing and being able to adhere to study restrictions and to be confined at the Clinical Research Unit.
排除标准
- •Clinically significant reported history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator;
- •Poor venous access;
- •Taken an investigational drug or participated in a clinical trial evaluating an investigational drug or device within 30 days (or 5 half-lives) prior to the study drug dose, whichever is longer;
- •Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the study drug dose;
- •Major surgery or hospitalization within 6 months prior to screening that in the Investigator's opinion would put the subject or study conduct at risk, or have any scheduled surgery or hospitalization during the study period;
- •Any condition or finding that in the Investigator's opinion would put the subject or study conduct at risk if the subject were to participate in the study.
研究组 & 干预措施
ziresovir
The study drugs will be administered to subjects by CRU staff at approximately 8:00 a.m. (± 1 hour), following an overnight fast.
Immediately following administration of the assigned dose of the study drugs, subjects will be given water such that their water consumption is approximately 240 mL as follows:
- If administered 60 mL as the study drug dose, follow with approximately 180 mL water.
- If administered 120 mL as the study drug dose, follow with approximately 120 mL water.
- If administered 180 mL as the study drug dose, follow with approximately 60 mL water.
干预措施: Ziresovir (Drug)
placebo
The study drugs will be administered to subjects by CRU staff at approximately 8:00 a.m. (± 1 hour), following an overnight fast.
Immediately following administration of the assigned dose of the study drugs, subjects will be given water such that their water consumption is approximately 240 mL as follows:
- If administered 60 mL as the study drug dose, follow with approximately 180 mL water.
- If administered 120 mL as the study drug dose, follow with approximately 120 mL water.
- If administered 180 mL as the study drug dose, follow with approximately 60 mL water.
干预措施: Placebo (Other)
结局指标
主要结局
change from baseline in pH from urinalysis
时间窗: screen/day -1/day 2/day4
numbers of all AEs
时间窗: through study completion, an average of 22 days
The Common Terminology Criteria for Adverse Events (CTCAE) Version 5 will be used to grade AEs
percentages of all AEs
时间窗: through study completion, an average of 22 days
The Common Terminology Criteria for Adverse Events (CTCAE) Version 5 will be used to grade AEs
change from baseline in systolic and diastolic blood pressure
时间窗: screen/day -1/day 1/day 2/day 3/day4
blood pressure in millimeter of mercury
change from baseline in pulse rate
时间窗: screen/day -1/day 1/day 2/day 3/day4
pulse rate in times per minute
change from baseline in respiratory rate
时间窗: screen/day -1/day 1/day 2/day 3/day4
respiratory rate in times per minute
change from baseline in oral temperature
时间窗: screen/day -1/day 1/day 2/day 3/day4
oral temperature in degree
change from baseline in Prothrombin time/International Normalized Ratio
时间窗: screen/day -1/day 2/day4
INR is calculated from the PT and allows for worldwide standardization of results.
change from baseline in Thrombin time
时间窗: screen/day -1/day 2/day4
Thrombin time in seconds
change from baseline in activated Partial Thromboplastin time
时间窗: screen/day -1/day 2/day4
activated Partial Thromboplastin time in seconds
change from baseline in Hemoglobin (Hgb) count
时间窗: screen/day -1/day 2/day4
Hemoglobin (Hgb) in gram per liter
change from baseline in Hematocrit (Hct)
时间窗: screen/day -1/day 2/day4
change from baseline in Platelet count
时间窗: screen/day -1/day 2/day4
Platelet count per liter
change from baseline in appearance of U-waves from resting 12-lead ECGs
时间窗: screen/day -1/day1/day2/day4
ECGs will be performed after the subject has been supine for at least 5 minutes
change from baseline in Red blood cell (RBC) count
时间窗: screen/day -1/day 2/day4
change from baseline in White blood cell (WBC) count with differential
时间窗: screen/day -1/day 2/day4
change from baseline in Specific gravity from urinalysis
时间窗: screen/day -1/day 2/day4
Incidence of abnormal physical findings
时间窗: screen/day -1/day2/day3/day4
full physical examination will be conducted at screening and an abbreviated physical exam will be conducted on Day -1 and Day 2. A symptom-directed physical exam will be conducted on Day 3 and Day 4.
change from baseline in Protein from urinalysis
时间窗: screen/day -1/day 2/day4
change from baseline in Glucose from urinalysis
时间窗: screen/day -1/day 2/day4
change from baseline in Ketones from urinalysis
时间窗: screen/day -1/day 2/day4
change from baseline in Bilirubin from urinalysis
时间窗: screen/day -1/day 2/day4
change from baseline in Blood from urinalysis
时间窗: screen/day -1/day 2/day4
change from baseline in Nitrites from urinalysis
时间窗: screen/day -1/day 2/day4
change from baseline in Leukocytes from urinalysis
时间窗: screen/day -1/day 2/day4
change from baseline in Urobilinogen from urinalysis
时间窗: screen/day -1/day 2/day4
Incidence of abnormal Microscopic urine analysis
时间窗: screen/day -1/day 2/day4
change from baseline in heart rate-corrected QT interval from resting 12-lead ECGs
时间窗: screen/day -1/day1/day2/day4
ECGs will be performed after the subject has been supine for at least 5 minutes
change from baseline in heart rate from resting 12-lead ECGs
时间窗: screen/day -1/day1/day2/day4
ECGs will be performed after the subject has been supine for at least 5 minutes
change from baseline in QRS intervals from resting 12-lead ECGs
时间窗: screen/day -1/day1/day2/day4
ECGs will be performed after the subject has been supine for at least 5 minutes
change from baseline in treatment-emergent T-wave morphology from resting 12-lead ECGs
时间窗: screen/day -1/day1/day2/day4
ECGs will be performed after the subject has been supine for at least 5 minutes
次要结局
- To characterize the drug concentration of ziresovir following single ascending doses by oral administration in healthy adult male and female subjects(0 (within 90 minutes prior to dosing) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, and 72 hours post-dose)