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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Antabio
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
The participants will receive 1 single dose of the combination of ANT3310 and meropenem (2 times a single dose in participants with ESRD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
ANT3310 and Meropenem
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.
干预措施: ANT3310 (Drug)
ANT3310 and Meropenem
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.
干预措施: Meropenem (Drug)
结局指标
主要结局
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
时间窗: 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
时间窗: 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
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.
Maximum Plasma Concentrations (Cmax) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.
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
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.
Fraction of dose recovered in urine (fe) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
时间窗: 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
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in urine.
Non-renal clearance (CLNonR) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in plasma and urine.
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
时间窗: 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
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in urine.
Mean residence time (MRT) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in plasma.
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
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in urine.
Dialysis clearance (CLD) of ANT3310 and Meropenem after a single i.v. infusion of the combination ANT3310-Meropenem in dialysed subjects
时间窗: during dialysis
Pharmacokinetic parameter of ANT3310 and Meropenem in dialysate and plasma.
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
时间窗: From pre-dose to Day 3
Pharmacokinetic parameter of ANT3310 and Meropenem in urine.
次要结局
- 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)
- Number of infusion site reactions to assess local venous tolerability(From pre-dose on Day 1 to Day 3)