Single-dose Tolerability Study of Benapenem for Injection in Phase I Clinical Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 98
- 主要终点
- Number of subjects with clinically significant findings in vital signs
研究概览
简要总结
To design 11 dose groups within 62.5 mg ~ 4000 mg for single-dose tolerability study. A single-center, randomized, blinded, placebo-controlled, dose escalation trial design is adopted. 8 subjects each in 62.5 mg, 125 mg, 3000 mg and 4000 mg dose groups, 10 subjects each in other groups, including 2 placebo-controlled subjects. To be carried out from low-dose group to high-dose group. The next dose group can be studied only when the observation of the previous dose group is completed and it is confirmed that the drug is safely tolerated. The test should be stopped in case of serious adverse reactions, or when more subjects experience adverse reactions and have reached termination criteria of the trial, even if the maximum dose has not been reached.
Infusion time is planned to be 30 min in 62.5 mg, 125 mg and 250 mg ; two infusion time, 30 min and 60 min, in 500 mg, 1000 mg and 2000 mg groups. If subjects can tolerate 60-min infusion, the same dose group at infusion time of 30 min is added. The 3000 mg and 4000 mg dose groups only receive 60-min infusion for investigation of tolerability.
详细描述
It is planned to design 11 dose groups within 62.5 mg ~ 4000 mg for single-dose tolerability study. A single-center, randomized, blinded, placebo-controlled, dose escalation trial design is adopted. There are 8 subjects each in 62.5 mg, 125 mg, 3000 mg and 4000 mg dose groups, and 10 subjects each in other groups. Each group consists of half males and half females, including 2 placebo-controlled subjects (1 male and 1 female). The trial is carried out from low-dose group to high-dose group. Each subject only receives one dose of test drug, which is dissolved in 100 mL of 0.9% NS, intravenous drip. During the trial, the adverse events of subjects should be closely followed. The next dose group can be studied only when the observation of the previous dose group is completed and it is confirmed that the drug is safely tolerated. The test should be stopped in case of serious adverse reactions, or when more subjects experience adverse reactions and have reached termination criteria of the trial, even if the maximum dose has not been reached.
In order to investigate possible effect of infusion rate on the tolerability and to ensure the safety of subjects, the infusion time is planned to be 30 min in 62.5 mg, 125 mg and 250 mg low-dose groups; two infusion time, 30 min and 60 min, in 500 mg, 1000 mg and 2000 mg groups. Under the circumstance that subjects can tolerate 60-min infusion, the same dose group at infusion time of 30 min is added to investigate the possible effect of infusion rate on the tolerability. The 3000 mg and 4000 mg dose groups only receive 60-min infusion for investigation of tolerability.
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
- Triple (Participant, Care Provider, 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
- •Male or female healthy subjects, aged 18~45;
- •Body weight ≥ 50 kg and body mass index 19.0~24.0 kg/m2;
- •Prior to the test, physical examination, blood routine, urine routine, liver and kidney functions, and related examinations normal, or mild abnormalities in indicators while without clinical significance as indicated by the investigator;
- •Normal or mild abnormalities without clinical significance in the standard 12-lead ECG;
- •Signing informed consent form
排除标准
- •Regular smoking, alcohol abuse, and drug abuse;
- •Use of drugs known damage to an organ within three months;
- •History of specific allergies, or history of drug allergy, especially those allergic to lactams and excipients of test drug;
- •Febrile illnesses within three days before the screening;
- •Patients with mental illness or psychotic disorder in the past;
- •Past mental and nervous system diseases (epilepsy, stroke, cerebrovascular disorder, etc.), gastrointestinal disorder (such as stomach ulcers, gastritis, etc.) or disorder of other systems (such as cardiovascular, respiratory, hematological, or endocrine system, etc.) diseases or medical history.
- •Habitually taking any medication, including traditional Chinese medicine;
- •Having taken any medication that may affect test results within two weeks before the screening, such as antibiotics, NSAIDs, aluminum- or magnesium-containing antacids, diuretics, anticoagulants, central nervous system depressants, and any drug that may affect the drug absorption;
- •Having participated in other investigational drug trial in the preceding three months;
- •Blood donation for 360 ml or more within three months before the screening;
- •Heart rate < 50 bpm or > 100 bpm;
- •Systolic blood pressure<90mmHg or ≥ 140mmHg, diastolic blood pressure ≥ 90 mmHg or < 60 mmHg;
- •Women who are pregnant or breastfeeding, or who may be pregnant without adopting acceptable contraception, or who have a positive result in serum pregnancy test;
- •Women who are planning to become pregnant within 6 months, or male subjects who are planning to make his spouse pregnant within 6 months;
- •HBsAg, HCV antibody, HIV antibody, and Treponema pallidum antibody positive;
- •Urine drug-of-abuse testing positive;
- •Any other factor that makes the subject not suitable for the trial as indicated by the investigator.
研究组 & 干预措施
Benapenem
Investigatial Product: Benapenem: 11 group : 62.5mg one dose; 125mg one dose;250mg one dose;500mg one dose 30min infusion;500mg one dose 60min infusion ;1000mg one dose 30min infusion; 1000mg one dose 60min infusion 2000mg one dose 30min infusion;2000mg one dose 60min infusion;3000mg one dose 60min infusion;4000mg one dose 60min infusion
干预措施: Benapenem (Drug)
Placebo
Placebo control 11 group : 62.5mg one dose;125mg one dose;250mg one dose;500mg one dose 30min infusion;500mg one dose 60min infusion ;1000mg one dose 30min infusion; 1000mg one dose 60min infusion 2000mg one dose 30min infusion;2000mg one dose 60min infusion;3000mg one dose 60min infusion;4000mg one dose 60min infusion
干预措施: Placebo (Drug)
结局指标
主要结局
Number of subjects with clinically significant findings in vital signs
时间窗: Change from Baseline at Day1, Day2, Day4 after dosing
Vitals signs such as systolic and diastolic blood pressure, heart rate, and pulse rate will be measured in a semi-supine position after 5 minutes of rest.
Number of subjects with clinically significant findings in laboratory parameters
时间窗: Change from Baseline at Day1, Day2, Day4 after dosing
Hematology and clinical chemistry and Urine Routine abnormalities will be monitored
Number of subjects with clinically significant 12-lead ECGs
时间窗: Change from Baseline at Day1, Day2, Day4 after dosing
Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals
次要结局
- AUC(0-24) of Benapenem(In each group: Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hour after dosing)
- Maximum observed plasma concentration (Cmax) of Benepenem(In each group: Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hour after dosing)
- Time to maximum observed plasma concentration (tmax) of Benapenem(In each group: Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hour after dosing)