Pharmacokinetics of Benapenem in Subjects With Renal Impairment

"Pharmacokinetics of Benapenem in Subjects With Mild or Moderate Renal Impairment "

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)

Study Overview

• Status: Completed
• Conditions: Complicated Urinary Tract Infection; Cuti
• Intervention / Treatment: Drug: benapenem

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Shanghai Tongji Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sihuan Pharmaceutical Holdings Group Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2019
• Primary Completion (ACTUAL): October 21, 2019
• Study Completion (ACTUAL): October 21, 2019

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (ACTUAL): July 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Urologic Diseases; Urinary Tract Infections
• Other Study ID Numbers: 5081-I-1004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No