Pharmacokinetics of Benapenem in Subjects With Renal Impairment

Phase 1

Completed

• Conditions: Complicated Urinary Tract Infection; Cuti
• Interventions: Drug: benapenem

• Registration Number: NCT04476407
• Lead Sponsor: Sihuan Pharmaceutical Holdings Group Ltd.

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-04
• Study Start: 2019-06-15
• Primary Completion: 2019-10-21
• Study Completion: 2019-10-21
• Study First Submitted: 2020-07-15
• Study First Submitted QC: 2020-07-15
• Last Update Submitted: 2020-07-15
• Study First Posted: 2020-07-20
• Last Update Posted: 2020-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
G2	benapenem	subjects with mild renal impairment
G1	benapenem	subjects with nomal renal function
G3	benapenem	subjects with moderate renal impairment

Primary Outcome Measures

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

Trial Locations

Locations (1)

Shanghai Tongji Hospital; 🇨🇳 Shanghai, Shanghai, China