Multiple-dose Tolerability and Pharmacokinetic Studies of Benapenem inClinical 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 clinical study.

Detailed Description
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A single-center, randomized, open-label, and dose escalation trial design is used in the multiple-dose tolerability and pharmacokinetic studies. The tolerability and pharmacokinetic studies are performed simultaneously. Three doses, 250 mg, 500 mg, and 1000 mg are proposed for multiple-dose tolerability and pharmacokinetic studies. The subjects are divided into two groups, 12 subjects in each group, half males and half females. 250 mg group is performed firstly. After completion of observation and confirming that the drug can be safely tolerated, study on 500 mg group is then performed. After completion of observation and confirming that the drug can be safely tolerated, study on 1000 mg group is then performed. Each subject only receives one dose, intravenous drip, once daily, for 7 consecutive days. During the trial, close attention is paid to the tolerability of subjects, and blood samples 4 mL is collected from cubital vein respectively before dosing, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 5h, 8 h, 12 h, and 24 h after dosing on Day 1 (0 h); before dosing (0 h), 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 5 h, 8 h, 12 h, 24 h, 36 h, and 48 h after dosing on Day 7 for pharmacokinetic study. Blood samples are collected before dosing on Day 4, 5 and 6 to determine the trough concentration for observing the pharmacokinetic profiles of benapenem and its major metabolites in the body after continuous dosing. 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

Official Title
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Multiple-dose Tolerability and Pharmacokinetic Studies of Benapenem for Injection in Phase Ib Clinical Healthy Subjects

Conditions
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Healthy Subject

Intervention / Treatment
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* Drug: Banapenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female healthy subjects, aged 18 45; Body weight ≥ 50 kg and body mass index 19.0 24.0 kg/m2; 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. Exclusion Criteria: Regular smoking, alcohol abuse, and drug abuse; Use of drugs with 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 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<50bpm or >100bpm; 12)Systolic blood pressure <90 mmHg or ≥140 mmHg, diastolic blood pressure ≥90mmHg or <60mmHg; 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.

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
Interventional Model Description: 250 mg group is performed firstly. After completion of observation and confirming that the drug can be safely tolerated, study on 500 mg group is then performed. After completion of observation and confirming that the drug can be safely tolerated, study on 1000 mg group is then performed
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Banapenem C1 group<br>250mg Once daily for 7 | Drug: Banapenem<br>* Banapenem to be used anti-infection<br>* Other names: 5081;|
| Experimental: Banapenem C2group<br>500mg Once daily for 7 | Drug: Banapenem<br>* Banapenem to be used anti-infection<br>* Other names: 5081;|
| Experimental: Banapenem C3group<br>1000mg Once daily for 7 | Drug: Banapenem<br>* Banapenem to be used anti-infection<br>* Other names: 5081;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-24) of Benapenem | AUC(0-24) is the area under the curve from time 0 to 24 hour | Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hours after Dosing | 
| Maximum observed plasma concentration (Cmax) of Benapenem | Maximum observed plasma concentration (Cmax) of Benapenem in healthy subjects | Pre dose and 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hours after 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 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hours after 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 0.25,0.5,0.75,1,1.5, 2, 2.5, 3, 4, 6,8,12, 24hours after 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, Day4 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, Day4 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 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 4 after dosing |