Renal Impairment
Conditions
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).
Interventions
DRUGANT3310
ANT3310 will be administered as a single intravenous infusion over 3 hours at a constant rate.
DRUGMeropenem
meropenem will be administered as a single intravenous infusion over 3 hours at a constant rate.
Sponsors
Clinical Research Center Kiel GmbH
Antabio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dialysis clearance (CLD) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem in dialysed subjects | during dialysis | Pharmacokinetic parameter of ANT3310 and Meropenem in dialysate and plasma. |
| 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 | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in urine. |
| Renal clearance (CLR) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in urine. |
| Fraction of dose recovered in urine (fe) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in urine. |
| 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 | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in urine. |
| 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 | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in urine. |
| 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 | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in urine. |
| Maximum Plasma Concentrations (Cmax) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| 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 | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| Time from dosing to maximum observed concentration (tmax) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| Apparent terminal elimination half-life (t1/2λz) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| 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 | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| 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 | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| Percentage of AUC0-inf obtained by extrapolation (AUCext) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| Total body clearance (CL) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| Non-renal clearance (CLNonR) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma and urine. |
| 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 | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
| Mean residence time (MRT) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem | From pre-dose to Day 3 | Pharmacokinetic parameter of ANT3310 and Meropenem in plasma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who discontinue due to a TEAE. | 0 hours to Day 9 | Percentage of participants who discontinue due to a TEAE. |
| 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 | Percentage of participants who meet the clinically significant abnormal criteria for safety laboratory tests at least once after start of dosing. |
| 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 | Percentage of participants meeting the clinically significant abnormal criteria for vital signs (blood pressure, pulse rate, respiratory rate, and body temperature) measurements at least once after start of dosing. |
| Number of participants who meet the clinically significant abnormal criteria for ECG (Electrocardiogram) parameters. | Day-1 to Day 9 | Percentage of participants who meet the clinically significant abnormal criteria for ECG parameters. |
| Number of infusion site reactions to assess local venous tolerability | From pre-dose on Day 1 to Day 3 | — |
| 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 | Percentage of participants experiencing ≥ one treatment-emergent adverse event (TEAE) by seriousness, intensity, and relatedness from baseline to end of study (EoS) or early withdrawal. |
Countries
Germany
Outcome results
None listed