A Randomized, Double-blind, Placebo-controlled Multiple-ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AP303 Following 2-week Oral Administration in Healthy Chinese Participants.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- AUC0-t
研究概览
简要总结
The study will be a single center, double-blind, randomized, placebo-controlled, multiple-ascending-dose study to evaluate the safety, tolerability, PK and PD of AP303 following 2-week oral administration to healthy Chinese participants.
详细描述
Eligible study participants will be enrolled and randomized into one of the two dose cohorts, each cohort will include 9 participants randomized to AP303 and placebo at 2:1 ratio (6 on AP303 and 3 on placebo).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female participants, 18-50 years of age.
- •BMI (body mass index) 18-27 kg/m
- •Important Exclusion criteria:
- •History or symptoms of any clinically significant kidney, liver, broncho-pulmonary, gastrointestinal, neurological, psychiatric, cardiovascular, endocrine/metabolic, hematological disease or cancer.
- •Personal history of congenital long QT syndrome or family history of sudden death.
- •People with a history of specific severe allergies, or severe allergic conditions or known allergies to the study or any of its ingredients or excipients as judged by the investigator, or any acute confirmed significant allergic reactions to any drug, or multiple drug severe allergies (non-active hay fever is acceptable). Allowing for childhood asthma, history of mild eczema that has had no flare ups for ≥5 years or is fully resolved.
- •History of having received or currently receiving any systemic anti-neoplastic or immunomodulatory treatment (including systemic oral or inhaled corticosteroids) ≤6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
- •Participants who have had significant acute infection, e.g., COVID-19, influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks before study drug administration.
- •Confirmed systolic BP greater than 140 or less than 90 mmHg, and diastolic BP greater than 90 or less than 50 mmHg at screening.
- •Abnormalities of ECG parameters and abnormal shape of ECG wave on screening ECG.
- •Implantation of cardiac pacemaker or clinically significant arrhythmias.
- •Estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 (using the CKD-EPI equation).
- •Positive test at screening of any of the following: Hepatitis B (HBsAg), Hepatitis C (HCVAb), human immunodeficiency virus (HIV Ab) or syphilis AB.
- •ALT or AST >1.5 × ULN, or any other clinically significant abnormalities in laboratory test results at screening.
- •Dosed with a small-molecule or biologic investigational drug within 30 days or 90 days, respectively, or 5 half-lives whichever is the longer) prior to first dose of this study.
- •Donation of component (plasma or platelet) or whole blood ≥200 mL within 4 weeks prior to screening.
- •Receipt of a live vaccine within 4 weeks of prior to screening (Influenza and COVID-19 vaccines are allowed).
- •Positive urine test for drugs of abus.
- •History of drug and/or alcohol abuse or addiction.
- •History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption within 48 hours before screening.
- •Use of >5 cigarettes or equivalent nicotine-containing product per day.
- •Taking any prescribed or over-the-counter medications (including vitamins or herbal remedies) within 30 days or 5 half-lives (whichever is the longer) of the first dose of study drug. Occasional paracetamol is allowed (see section on Permitted Therapy). Exceptions may be made on a case-by-case basis following discussion and agreement between the investigator and the sponsor.
- •Medical or social conditions that would potentially interfere with the participant's ability to comply with the study visit schedule or the study assessments.
排除标准
- 未提供
研究组 & 干预措施
AP303
干预措施: AP303 150 μg (Drug)
AP303
干预措施: AP303 300 μg (Drug)
Placebo
干预措施: Placebo 150 μg (Drug)
Placebo
干预措施: Placebo 300 μg (Drug)
结局指标
主要结局
AUC0-t
时间窗: Day 3-14
Area under the plasma concentration-time curve for a dosing interval
CL/F
时间窗: Day 1
Apparent oral clearance calculated from Dose/ AUC0-inf
Tmax
时间窗: Day 1, Day 3-14
Time to maximum observed plasma concentration
AUC0-last
时间窗: Day 1
Area under the plasma concentration versus time curve up to the last measurable concentration
Cmax
时间窗: Day 1, Day 3-14
Maximum observed plasma concentration
AUC0-24h
时间窗: Day 1
Area under the plasma concentration versus time curve up to 24 hours
t1/2
时间窗: Day 1, Day 3-14
Apparent terminal half-life, computed as ln(2)/λz
V/F
时间窗: Day 1, Day 3-14
Apparent volume of distribution of oral drug
Cav
时间窗: Day 3-14
average plasma concentration
Ctrough
时间窗: Day 3-14
Trough plasma concentration
Rac
时间窗: Day 3-14
Ratio of accumulation
Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results
时间窗: Day 1-28
Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results
Effect of AP303 on ECG parameters
时间窗: Day 1-28
QTcB in ms
Vital signs
时间窗: Day 1-28
Effect of AP303 on vital signs, e.g. blood pressure
Effect of AP303 on physical examination result
时间窗: Day 1-28
nature, frequency, and severity of abnormality of physical examination result
body weight
时间窗: Day 1-28
Effect of AP303 on body weight, e.g. change of body weight after administration of AP303
Incidence and severity of adverse events
时间窗: Day 1-28
Incidence and severity of adverse events
AUC0-inf
时间窗: Day 1
Area under the plasma concentration versus time curve extrapolated to infinity
次要结局
- Fasting lipid profile(Baseline, Days 5, 10, 14 and 28)
- Serum creatinine(Baseline, Days 5, 10, 14 and 28)
- Fasting glucose(Baseline, Days 5, 10, 14 and 28)
- eGFR(Baseline, Days 5, 10, 14 and 28)