Assessment of the Pharmacokinetics and Safety of ANT3310 Combined With Meropenem in Renally Impaired Subjects

NCT06527677 | Completed Phase 1 DMC

• 1 other identifier: ANT3310-1002
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, non-randomized, single-center, single i.v. dose Phase 1 trial to evaluate the pharmacokinetics and safety of a combination of ANT3310 and meropenem in participants with different degrees of renal function impairment, including participants with End-Stage Renal Disease (ESRD), compared with matching control participants with normal renal function.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (18)

• Maximum Plasma Concentrations (Cmax) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Area under the curve from 0 to infinity (AUC0-inf) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Time from dosing to maximum observed concentration (tmax) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Apparent terminal elimination half-life (t1/2λz) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Area under the curve from time 0 to time of last measurable concentration (AUC0-last) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Area under the curve from time 0 to 48h (AUC0-48h) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Percentage of AUC0-inf obtained by extrapolation (AUCext) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Total body clearance (CL) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Non-renal clearance (CLNonR) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma and urine.

  From pre-dose to Day 3

• Apparent volume of distribution during the terminal phase after administration (Vz) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Mean residence time (MRT) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.

  From pre-dose to Day 3

• Amount of ANT3310 and Meropenem that is eliminated in urine from 0 to infinity (Ae0-inf) after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in urine.

  From pre-dose to Day 3

• Renal clearance (CLR) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in urine.

  From pre-dose to Day 3

• Fraction of dose recovered in urine (fe) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in urine.

  From pre-dose to Day 3

• Amount of ANT3310 and Meropenem that is eliminated in urine from 0 to 48h (Ae0-48h) after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in urine.

  From pre-dose to Day 3

• Fraction of dose recovered in urine from 0 to 48 hours (fe0-48h) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in urine.

  From pre-dose to Day 3

• Renal clearance from 0 to 48 hours (CLR[0-48h]) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem

  Pharmacokinetic parameter of ANT3310 and Meropenem in urine.

  From pre-dose to Day 3

• Dialysis clearance (CLD) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem in dialysed subjects

  Pharmacokinetic parameter of ANT3310 and Meropenem in dialysate and plasma.

  during dialysis

Secondary Outcomes (6)

• Number and severity of treatment-emergent adverse event (TEAE) to evaluate the safety and tolerability of ANT3310 and meropenem after a single i.v. infusion of a combination of ANT3310 and meropenem.

  0 hours to Day 9

• Number of participants who discontinue due to a TEAE.

  0 hours to Day 9

• Number of participants who meet the clinically significant abnormal criteria for safety laboratory tests at least once after start of dosing.

  0 hours to Day 9

• Number of participants meeting the clinically significant abnormal criteria for vital signs measurements at least once after start of dosing.

  0 hours to Day 9

• Number of participants who meet the clinically significant abnormal criteria for ECG (Electrocardiogram) parameters.

  Day-1 to Day 9

Study Arms (1)

ANT3310 and Meropenem

EXPERIMENTAL

Participants with mild, moderate, or severe renal function impairment (Panel A, B, and D) and participants with normal renal function (Panel C and F) will receive 1 single dose of a combination of ANT3310 and meropenem. Participants with End Stage Renal Disease (Panel E) will receive 2 times a single dose of a combination of ANT3310 and meropenem: one single dose during dialysis-free interval ("off- dialysis") and one single dose on the day of dialysis ("on-dialysis"). The same dose will be given in both periods with a washout interval of at least 7 days between administrations.

Drug: ANT3310; Drug: Meropenem

Interventions

ANT3310 DRUG

ANT3310 will be administered as a single intravenous infusion over 3 hours at a constant rate.

ANT3310 and Meropenem

Meropenem DRUG

meropenem will be administered as a single intravenous infusion over 3 hours at a constant rate.

ANT3310 and Meropenem

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 to 80 years of age (both inclusive) at the time of signing the informed consent.
• BMI within the range of 18.0 to 36.0 kg/m2 (both inclusive) with a body weight ≥ 50 kg.
• Contraceptive use by women or men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent in compliance with the requirements and restrictions listed in the ICF and in the protocol.
• Ability to cooperate with the investigator and to comply with the requirements of the trial.
• Sufficient venous access for i.v. infusion and PK samplings.
• For participants with renal function impairment: Individualized eGFR \<90 mL/min at screening, estimated according to the individualized CKD-EPI equation and stable renal function.
• For participants with ESRD requiring dialysis: Chronic intermittent hemodialysis for ≥3 months prior to dosing.
• For participants with normal renal function: Individualized eGFR ≥90 mL/min at screening, estimated based on serum creatinine measured within 10 days prior to Day -1 according to the CKD-EPI equation.

You may not qualify if:

• Febrile illness within 1 week before admission to the study center.
• Known hypersensitivity to meropenem and or ANT3310 or any of the excipients of the infusion solution.
• Known severe allergies, non-allergic drug reactions, or multiple drug allergies requiring intranasal or systemic corticosteroids during any time of the year or history of any anaphylactic reaction.
• Medical disorder, condition, or history of such that would - in the opinion of the investigator - compromise the participant's ability to participate in this study.
• History of epilepsy (or known seizure disorder), brain lesions or other significant neurological disorders.
• Known history of clinically significant hypersensitivity or urticaria, or severe allergic reaction to β-lactam antibiotics (e.g., penicillin, cephalosporin, carbapenem, or monobactam).
• History of Gilbert syndrome.
• History of any severe antibiotic-associated superinfections like Clostridium difficile colitis and/or frequent fungal vaginal infections.
• Therapies (e.g., physiotherapy, acupuncture, etc.) within 1 week before study drug administration.
• Positive results for HBsAg, anti-HCV, HIV antibodies (anti-HIV 1+2).
• For participants with impaired renal function: Acute renal failure or active renal infections, Clinically significant impaired hepatic function, Severe infection or any clinically significant illness within 4 weeks before dosing, Impairment of any other major organ system other than the kidney except underlying disease, Diagnosed malignancy during the past 5 years except completely resected basal cell cancer of the skin, Any kidney transplant during the last 10 years, any other organ transplant during the past 5 years.

Sponsors & Collaborators

• Antabio: lead
• Clinical Research Center Kiel GmbH: collaborator

Study Sites (1)

CRS Clinical Research Services Kiel GmbH

Kiel, D-24105, Germany

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Meropenem

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Christian Zwingelstein, PharmD

  Antabio

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 30, 2024
• Study Start: July 19, 2024
• Primary Completion: July 3, 2025
• Study Completion: July 10, 2025
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)