A Randomized, Double-Blind, Placebo Controlled, Phase I Study to Assess, Safety, Tolerability, Pharmacokinetics of HS-10383 Administered Orally in China Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Safety and Tolerability Evaluation
研究概览
简要总结
This is a first-in-human study that will investigate the safety, tolerability and pharmacokinetics of ascending single doses of HS-10383 using a randomized, double blind, placebo controlled, single center study design.
Participants in this study will receive either the study drug or placebo tablets (a placebo looks like the test drug but does not have any medicine in it). The dosage will be one single dose of study drug/placebo received on only one day. The total study duration for each participant will be usually no more than 10 days. Blood samples will be collected from the participants to monitor the safety and measure the blood level of the study drug.
详细描述
HS-10383 is a selective P2X3 receptor antagonist being developed for the treatment of refractory/unexplained chronic cough. This Phase 1 study will investigate the safety, tolerability and pharmacokinetics of ascending single doses of HS-10383 administered orally to healthy volunteers.
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
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants aged from 18 to 45 years ;
- •Subjects need to fully understand the research content and process, as well as possible adverse reactions, and voluntarily sign the informed consent;
- •Male weight ≥ 50kg, female weight ≥ 45kg, body mass index {BMI, BMI=weight/height 2 (kg/m2)} is controlled within the range of 18~26 (including the critical value);
- •Subjects need to agree to take effective contraceptive methods from the screening date to 90 days after the last dose;
- •Male subjects must agree not to donate sperm within 90 days from the start of the administration to the last administration.
排除标准
- •The following medical histories, such as neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal muscle system, metabolic endocrine system, skin disease, blood system, immune system and tumor, etc., were screened. evaluated as unsuitable to participate in this study;
- •Any known presence or history of hypogeusia, abnormal taste or dysgeusia;
- •Any known presence or history of severe allergies, or known to be allergic to the components of the test drug;
- •Use of any drugs, including prescription drugs, over-the-counter drugs or herbal preparations, cannot be avoided or expected to start 2 weeks (or 5 half-lives) before screening and throughout the study period;
- •Any findings of electrocardiogram outside from normal, such as the QT interval (QTcF) corrected by the Fridericia formula, the absolute value of QTcF for males is >450 ms, and the absolute value of QTcF for females is >470 ms;
- •Any findings of blood pressure or pulse in resting state outside from normal a: such as systolic blood pressure <90 mmHg or ≥140 mmHg, diastolic blood pressure <60 mmHg or ≥90 mmHg, pulse <55 bpm or >100 bpm;
- •Serum creatinine exceeds the upper limit of normal (ULN) at screening;
- •Infectious diseases with hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody test were positive at the time of screening;
- •Any findings from the medical examination (comprehensive physical examination, vital signs, blood oxygen saturation, laboratory tests, abdominal B-ultrasound and chest X-ray ) outside from normal and deemed by the investigator to be clinically significant;
- •Drug abusers, or have used soft drugs (such as marijuana) within 3 months prior to screening, or have taken hard drugs (such as cocaine, phencyclidine, etc.) within 1 year before screening;
- •Volunteers who with a positive alcohol breath test at screening, with a history of alcohol abuse or a single consumption of more than 14 units of alcohol in the past two weeks (1 unit = 285 mL of beer, 25 mL of spirits, and 150 mL of wine);
- •Smokers or those who smoked more than 5 cigarettes per day within 3 months prior to screening, or those who could not stop using any tobacco products (including e-cigarettes) during the study;
- •Average daily intake of coffee or tea ≥ 5 cups (200mL/cup) within 3 months prior to screening;
- •Volunteers who donated or lost 250 mL more of blood in 3 months prior to screening, or had undergone major surgery in the past;
- •Volunteers who participated in any clinical trials and took any clinical trial drugs within 3 months prior to screening;
- •Difficulty swallowing solid preparations such as capsules or tablets;
- •Within 30 days prior to screening, for whatever reason, dieting or receiving dietary therapy, or major changes in dietary habits;
- •Within 30 days prior to screening and during the entire study period, consuming beverages or foods containing grapefruit (such as grapefruit, lime, star fruit, etc.), or products containing St. John's wort cannot be avoided;
- •Female subjects are pregnant or breastfeeding at the screening;
- •Females of childbearing potential with positive urine β-human chorionic gonadotropin (β-hCG) at screening, or positive serum β-hCG at baseline (day -1);
- •Volunteers who have difficulty in blood collection and cannot tolerate multiple venous blood collection and any contraindications to blood collection;
- •Volunteers who have a history of vaccination within 30 days prior to screening, or who have a vaccination plan throughout the study period;
- •As determined by the investigator, any physical or psychological disease or condition that may increase the risk of the study, affect the subject's compliance with the protocol or affect the subject's completion of the study.
研究组 & 干预措施
HS-10383
HS-10383 was administered at 8 am on the first day, 4 dose levels
干预措施: HS-10383 (Drug)
HS-10383 Placebo
Matching placebo to HS-10383 was administered at 8 am on the first day, 4 dose levels
干预措施: HS-10383 Placebo (Drug)
结局指标
主要结局
Safety and Tolerability Evaluation
时间窗: up to 9 days
1. Adverse events (AEs), serious adverse events (SAEs) and adverse events leading to withdrawal from the study, the incidence, severity and correlation with the trial drug; 2. Changes in laboratory tests (blood routine, urine routine, blood biochemistry and coagulation function) before and after administration; 3. Changes in vital signs (respiration, pulse, blood pressure and body temperature) and SpO2 before and after administration; 4. Electrocardiogram (ECG) to check the changes before and after administration.
次要结局
- Area Under the Concentration-time Curve0-∞(up to 9 days)
- Clearance Rate(up to 9 days)
- Apparent Volume of Distribution(up to 9 days)
- Mean Retention Time(up to 9 days)
- Maximum plasma concentration (Cmax)(up to 9 days)
- Time of Maximum Concentration(up to 9 days)
- Terminal Rate Constant(up to 9 days)
- Area Under the Concentration-time Curve0-t(up to 9 days)
- Elimination Halflife(up to 9 days)