Multiple-dose Tolerability and Pharmacokinetic Studies of Benapenem in Clinical Healthy Subjects

Study Overview
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Brief Summary
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To observe the pharmacokinetic profiles of benapenem and its major metabolites in healthy volunteers after continuous multiple-dose benapenem, providing evidence for phase Ⅱ/Ⅲclinical study.

Official Title
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Multiple-dose Tolerability and Pharmacokinetic Studies of Benapenem in Clinical Healthy Subjects

Conditions
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Multiple-dose Tolerability and Pharmacokinetic Studies of Benapenem in Clinical Healthy Subjects

Intervention / Treatment
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* Drug: Banapenem
* Drug: sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1、 Male or female healthy subjects, aged 18 45(including 18 and 45 years); 2、Body weight ≥ 50 kg and body mass index 19.0 24.0 kg/m2; 3、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 ; 4、Normal or mild abnormalities without clinical significance in the standard 12-lead ECG; 5、 Signing informed consent form. Exclusion Criteria: 1、Having a serious systemic disease, infectious disease or mental disorder; 2、Regular smoking, alcohol abuse, and drug abuse ; 3、Use of drugs known damage to an organ within three months; 4、History of specific allergies, or history of drug allergy, especially those allergic to lactams and excipients of test drug; 5、Febrile illnesses within three days before the screening; 6、Patients with mental illness or psychotic disorder in the past; 7、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; 8、Habitually taking any medication, including traditional Chinese medicine; 9、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; 10、Having participated in other investigational drug trial in the preceding three months; 11、Blood donation for 360 ml or more within three months before the screening; 12、Heart rate < 50 bpm or > 100 bpm; 13、Systolic blood pressure<90mmHg or ≥ 140mmHg, diastolic blood pressure ≥ 90 mmHg or <60mmHg ; 14、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; 15、Women who are planning to become pregnant within 6 months, or male subjects who are planning to make his spouse pregnant within 6 months; 16、HBsAg, HCV antibody, HIV antibody, and Treponema pallidum antibody positive; 17、Urine drug-of-abuse testing positive; 18、Any other factor that makes the subject not suitable for the trial as indicated by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Banapenem<br>2000 mg group is performed firstly. After completion of observation and confirming that the drug can be safely tolerated, study on 3000 mg group is then performed | Drug: Banapenem<br>* 2000 mg group is performed firstly. After completion of observation and confirming that the drug can be safely tolerated, study on 3000 mg group is then performed<br>|
| Placebo Comparator: placebo<br>sodium chloride injection Once daily for 7 days | Drug: sodium chloride<br>* sodium chloride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-t) of Benapenem | AUC(0-t) is the area under the curve from time 0 to t | Pre dose and 0.25,1,1.25,1.5, 2, 3,5,8,12, 24,72,96,120,144,144.5,145,145.25,145.5,146,147,149,152,156,168,180,192hours after first Dosing | 
| Maximum observed plasma concentration (Cmax) of Benapenem | Maximum observed plasma concentration (Cmax) of Benapenem in healthy subjects | Pre dose and 0.25,1,1.25,1.5, 2, 3,5,8,12, 24,72,96,120,144,144.5,145,145.25,145.5,146,147,149,152,156,168,180,192hours after first Dosing | 
| Time to maximum observed plasma concentration (tmax) of Benapenem | Time to maximum observed plasma concentration (tmax) of Benapenem in healthy subjects | Pre dose and 0.25,1,1.25,1.5, 2, 3,5,8,12, 24,72,96,120,144,144.5,145,145.25,145.5,146,147,149,152,156,168,180,192hours after first Dosing | 
| Time to elimination half-life (t1/2) of Benapenem | Time to elimination half-life (t1/2) of Benapenem in healthy subjects | Pre dose and 0.25,1,1.25,1.5, 2, 3,5,8,12, 24,72,96,120,144,144.5,145,145.25,145.5,146,147,149,152,156,168,180,192hours after first Dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with clinically significant findings in vital signs | 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 | Screening, Day1, Day2, Day3, Day4, Day5, Day6, Day7, Day8, Day9, Day10 after Dosing | 
| Number of subjects with clinically significant findings in laboratory parameters | Hematology and Clinical Chemistry and Urine routine abnormalities will be monitored | Screening, Day1, Day2, Day3, Day4, Day5, Day6, Day7, Day8, Day9, Day10 after Dosing | 
| Number of subjects with clinically significant 12-lead ECGs | 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. | Screening, Day1, Day2, Day4, Day5,Day7, Day8, Day10 after Dosing | 
| Number of subjects with adverse events and serious adverse events | All adverse events will be monitored in each group subjects | From Screening to Day 10 after dosing |