Pharmacokinetics of Benapenem in Subjects With Renal Impairment

Study Overview
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Brief Summary
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This is an open-label, multiple center, parallel-group Study to compare the pharmacokinetics and safety of single-dose benapenem (1.0mg) in subjects with mild or moderate Renal Impairment(RI) and healthy subjects. Subjects were enrolled with defined degrees of RI based on eGFR(estimated Glomerular Filtration Rate) calculated by MDRD (Modification of Diet in Renal Disease)formular as follows: nomal renal function(≥90ml/min/1.73m2 ; N=6); mild RI (60-89mL/min/1.73 m2 ; N=6), moderate RI (30-59 mL/min/1.73m2 ; N=6)

Official Title
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Pharmacokinetics of Benapenem in Subjects With Mild or Moderate Renal Impairment 

Conditions
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Complicated Urinary Tract Infection; Cuti

Intervention / Treatment
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* Drug: benapenem
* Drug: benapenem
* Drug: benapenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.18 75 years old 2. BMI 17 to 30 kg/m2 3. No known diseases or significant abnormalities on physical exam (subjects with normal renal function only) 4. eGFR ≥ 90 mL/min/1.73m2 (subjects with normal renal function only) 5. eGFR 30 to 59 mL/min/1.73m2 (subjects with mild renal impairment only); eGFR 60 to 89 mL/min/1.73m2 (subjects with moderate renal impairment only) Exclusion Criteria: 1. Hypersensitivity to any of the beta-lactam antibiotics 2.Conditions or disease that may interfere with the evaluation of study drug 3. Acute disease requiring antibiotics within 30 days prior to administration, or a fever within 7 days prior to administration; 4. Drug abuse in 2 years 5. A blood donation or more than 400 ml of blood loss within 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G1<br>subjects with nomal renal function | Drug: benapenem<br>* single-dose Benapenem 1.0mg(iv), 60min infusion<br>|
| Experimental: G2<br>subjects with mild renal impairment | Drug: benapenem<br>* single-dose Benapenem 1.0mg(iv), 60min infusion<br>|
| Experimental: G3<br>subjects with moderate renal impairment | Drug: benapenem<br>* single-dose Benapenem 1.0mg(iv), 60min infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve | Area under the plasma concentration-time curve from time 0 to the time of thelast quantifiable concentration (AUC0-t )of benapenem and the metabolite | predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose | 
| Area under the plasma concentration-time curve | Area under the plasma concentration-time curve from time 0 to infinity ( AUC0-inf ) of benapenem and the metabolite | predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose | 
| Maximum observed plasma concentration(Cmax) | Maximum observed plasma concentration(Cmax) of benapenem and the metabolite | predose and 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48, 72 hours postdose | 
| Observed terminal elimination half-life (T1/2) | Observed terminal elimination half-life (T1/2) of benapenem and its metabolite | predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose | 
| Total body clearance (CLt) | Total body clearance (CLt) of benapenem | predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose | 
| Apparent volume of distribution (Vz) | Apparent volume of distribution (Vz) based on the terminal phase of benapenem | predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose | 
| Cumulative urine exeretion | Cumulative urine exeretion (Ae0-72h%) of benapenem and its metabolite | predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose | 
| Renal clearance (CLr) | Renal clearance (CLr) of Benapenem and its metabolite | predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose | 
| Metabolite-to-parent ratio of AUC0-inf | Metabolite-to-parent ratio of AUC0-inf (MR) | predose, 0.5, 1.25, 1.5, 2, 3, 5, 8, 12, 24, 48 and 72 hours postdose |