Clinical trial NCT06527677: Assessment of the Pharmacokinetics and Safety of ANT3310 Combined With Meropenem in Renally Impaired Subjects
Official title: Phase 1, Open-Label, Non-Randomized, Single-Center, Single-Dose Study to Assess the Pharmacokinetics & Safety of ANT3310 Combined With Meropenem Administered as a Single Intravenous Infusion to Adult Subjects With Renal Function Impairment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Antabio
Sponsor class: INDUSTRY
Collaborators: name: Clinical Research Center Kiel GmbH
First posted: 2024-07-30
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Detailed description: The participants will receive 1 single dose of the combination of ANT3310 and meropenem (2 times a single dose in participants with ESRD).

Eligibility criteria: Main Inclusion Criteria:

* 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.

Main Exclusion Criteria:

* 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.

Primary outcomes:
measure: Maximum Plasma Concentrations (Cmax) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: 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
timeFrame: From pre-dose to Day 3
measure: Time from dosing to maximum observed concentration (tmax) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: Apparent terminal elimination half-life (t1/2λz) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: 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
timeFrame: From pre-dose to Day 3
measure: 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
timeFrame: From pre-dose to Day 3
measure: Percentage of AUC0-inf obtained by extrapolation (AUCext) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: Total body clearance (CL) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: Non-renal clearance (CLNonR) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: 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
timeFrame: From pre-dose to Day 3
measure: Mean residence time (MRT) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: 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
timeFrame: From pre-dose to Day 3
measure: Renal clearance (CLR) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: Fraction of dose recovered in urine (fe) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
timeFrame: From pre-dose to Day 3
measure: 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
timeFrame: From pre-dose to Day 3
measure: 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
timeFrame: From pre-dose to Day 3
measure: 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
timeFrame: From pre-dose to Day 3
measure: Dialysis clearance (CLD) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem in dialysed subjects
timeFrame: during dialysis
Secondary outcomes:
measure: 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.
timeFrame: 0 hours to Day 9
measure: Number of participants who discontinue due to a TEAE.
timeFrame: 0 hours to Day 9
measure: Number of participants who meet the clinically significant abnormal criteria for safety laboratory tests at least once after start of dosing.
timeFrame: 0 hours to Day 9
measure: Number of participants meeting the clinically significant abnormal criteria for vital signs measurements at least once after start of dosing.
timeFrame: 0 hours to Day 9
measure: Number of participants who meet the clinically significant abnormal criteria for ECG (Electrocardiogram) parameters.
timeFrame: Day-1 to Day 9
measure: Number of infusion site reactions to assess local venous tolerability
timeFrame: From pre-dose on Day 1 to Day 3
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: CRS Clinical Research Services Kiel GmbH
Study officials:
affiliation: Antabio
name: Christian Zwingelstein, PharmD
role: STUDY_DIRECTOR
References: