Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single- and Multiple-Ascending Doses of Intravenous ANT3310 Alone and in Combination With Meropenem in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Antabio
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Number and severity of Treatment Emergent Adverse Events (TEAE) to evaluate the safety and tolerability profile of single and multiple intravenous ascending doses of ANT3310 alone (Part A and B) and in combination with meropenem (Part C)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of single and multiple intravenous ascending doses of ANT3310, a novel, specific, competitive inhibitor of serine β-lactamases, alone and in combination with meropenem in healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant capable of giving signed informed consent
- •Contraceptive use by women or men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Participants are overtly healthy as determined by a medical evaluation including medical history without clinically relevant pathologies, physical examination, vital signs, ECG assessment, and clinical laboratory result
- •eGFR ≥ 90 mL/min and < 160 mL/min for males or < 150 mL/min for females
- •Body weight within 50.0 and 100.0 kg and BMI within 18.0 and 30.0 kg/m2
排除标准
- •History of any clinically-relevant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrine, haematologic, neuromuscular or allergic disease(s), metabolic disorder, cancer, cirrhosis, significant acute infection, local infection within 2 weeks of dose administration,
- •ECG: any history of clinically-significant ECG abnormalities, an uninterpretable ECG, or any of ECG abnormalities, unless considered not significant by the Investigator
- •Abnormalities in clinical chemical, haematological, or coagulation variables considered medically relevant by the Investigator,
- •Positive urine drug screen, positive breathalyzer for alcohol
- •Positive results in any of the following virology tests: HIV-1 and -2 antibodies, HBsAg, and anti-hepatitis C virus antibody
- •Positive SARS-CoV-2 antigen test
- •Women who are pregnant or nursing,
- •Donation or loss of over 500 mL of blood within sixty days prior to the first study drug administration,
- •Part C with co-administration of meropenem:
- •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,
- •History of Gilbert syndrome,
- •History of any severe antibiotic-associated superinfections,
研究组 & 干预措施
Part A: Single Intravenous Ascending Dose of ANT3310
干预措施: ANT3310 (Drug)
Part A: Single Intravenous Dose of Matching placebo
干预措施: ANT3310-placebo (Drug)
Part B: Multiple Intravenous Ascending Doses of ANT3310
干预措施: ANT3310 (Drug)
Part B: Multiple Intravenous Ascending Doses of Matching Placebo
干预措施: ANT3310-placebo (Drug)
Part C: ANT3310 + Meropenem
Participants will receive a single intravenous dose of ANT3310 or Meropenem in one of the 2 treatment sequences followed by the repeat administrations of ANT3310 + Meropenem.
干预措施: ANT3310 (Drug)
Part C: ANT3310 + Meropenem
Participants will receive a single intravenous dose of ANT3310 or Meropenem in one of the 2 treatment sequences followed by the repeat administrations of ANT3310 + Meropenem.
干预措施: Meropenem (Drug)
Part C: ANT3310 Placebo + Meropenem Placebo
Participants will receive a single dose of ANT3310-placebo or Meropenem-placebo in one of the 2 treatment sequences followed by repeat administrations of ANT3310-placebo + Meropenem-placebo
干预措施: ANT3310-placebo (Drug)
Part C: ANT3310 Placebo + Meropenem Placebo
Participants will receive a single dose of ANT3310-placebo or Meropenem-placebo in one of the 2 treatment sequences followed by repeat administrations of ANT3310-placebo + Meropenem-placebo
干预措施: Meropenem-placebo (Drug)
结局指标
主要结局
Number and severity of Treatment Emergent Adverse Events (TEAE) to evaluate the safety and tolerability profile of single and multiple intravenous ascending doses of ANT3310 alone (Part A and B) and in combination with meropenem (Part C)
时间窗: up to 11 days
Percentage of subjects who experience at least one TEAE, including abnormalities in vital signs, physical examinations, laboratory safety tests and ECG, by seriousness, intensity, and relatedness
次要结局
- Part A (SAD): Maximum Plasma Concentration (Cmax) of single i.v. ascending doses of ANT3310 alone(24 hours)
- Part A (SAD): Time to maximum plasma concentration (Tmax) of single i.v. ascending doses of ANT3310 alone(24 hours)
- Part A (SAD): Half-time (t1/2) of single i.v. ascending doses of ANT3310 alone(24 hours)
- Part B (MAD): Time to maximum plasma concentration (Tmax) of multiple i.v. ascending doses of ANT3310 alone(Day 1, Day 7)
- Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of multiple i.v. dose of ANT3310 co-administered with meropenem(Day 11)
- Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of multiple i.v. dose of ANT3310 co-administered with meropenem(Day 11)
- Part C (DDI and combination): Maximum Plasma Concentration (Cmax) of a single i.v. dose of ANT3310 and meropenem(Day 1, Day 3, Day 5)
- Part C (DDI and combination): Time to maximum plasma concentration (Tmax) of a single i.v. dose of ANT3310 and meropenem(Day 1, Day 3, Day 5)
- Part C (DDI and combination): Area under the concentration time curve (AUC) of multiple i.v. dose of ANT3310 co-administered with meropenem(Day 11)
- Part A (SAD): Area under the concentration time curve (AUC) of single i.v. ascending doses of ANT3310 alone(24 hours)
- Part B (MAD): Maximum Plasma Concentration (Cmax) of multiple i.v. ascending doses of ANT3310 alone(Day 1, Day 7)
- Part B (MAD): Area under the concentration time curve (AUC) of multiple i.v. ascending doses of ANT3310 alone(Day 1, Day 7)
- Part C (DDI and combination): Area under the concentration time curve (AUC) of a single i.v. dose of ANT3310 and meropenem(Day 1, Day 3, Day 5)