A Phase 1, Randomized, Open-Label, Trial Evaluating the Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Intravenous Carbavance™ (RPX2014/RPX7009) in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Pharmacokinetics from baseline through the end of the study
研究概览
简要总结
RPX7009(beta-lactamase inhibitor) is being studied in combination with a carbapenem (RPX2014) to treat bacterial infections, including those due to multi-drug resistant bacteria.
详细描述
The worldwide spread of resistance to antibiotics among Gram-negative bacteria, particularly members of the ESKAPE group of pathogens, has resulted in a crisis in the treatment of hospital acquired infections. In particular, the recent dissemination of a serine carbapenemase (e.g., KPC) in Enterobacteriaceae in US hospitals now poses a considerable threat to the carbapenems and other members of the beta-lactam class of antimicrobial agents.
Rempex is developing a fixed combination antibiotic of a carbapenem (RPX2014) plus a new beta-lactamase inhibitor (RPX7009) which has activity against serine beta-lactamases, including KPC. This Phase 1 study will assess the pharmacokinetics of intravenous RPX2014 and RPX7009 in plasma and epithelial fluid.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Healthy adult males and/or females, 18 to 55 years of age (inclusive) at the time of screening.
- •Body mass index (BMI) ≥ 18.5 and ≤ 30 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive) at the time of screening.
- •Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, electrocardiograms (ECGs), physical examination) as deemed by the PI.
- •Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to Day
- •Voluntarily consent to participate in the study.
排除标准
- •History or presence of significant oncologic, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
- •Positive urine drug/alcohol testing at screening (or Day -1).
- •Positive testing for human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg).
- •History or presence of alcoholism or drug abuse within the 2 years prior to Day
- •Hypersensitivity or idiosyncratic reaction to beta-lactam antibiotics (e.g. penicillins, cephalosporins, carbapenems, etc.).
- •Clinically significant pulmonary or any other disease that prevents a subject from undergoing bronchoscopy with bronchopulmonary lavage.
- •History of seizures (e.g., epilepsy), head injury or meningitis requiring ongoing anti-seizure medications.
- •Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to Day
- •Participation in another investigational clinical trial within 30 days prior to Day
- •Females who are pregnant or lactating.
- •Surgery within the past three months prior to Day 1 determined by the PI to be clinically relevant.
- •Any acute illness including clinically significant infection within 30 days prior to Day
- •QTcF interval >450 msec, or history of prolonged QT syndrome at screening (or Day 1).
- •Calculated creatinine clearance less than 80 mL/min (Cockroft-Gault method) at screening.
- •Subjects who have any clinically significant abnormalities on laboratory values at screening (or Day -1), including:
- •White blood cell count (WBC) < 3,000/mm3, hemoglobin < 11g/dL.
- •Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm
- •Liver function abnormalities at screening (or Day -1) (defined by an elevation in bilirubin, AST or ALT 1.5 x ULN of the normal range for subjects based on age and sex).
研究组 & 干预措施
Multiple dose of Carbavance (RPX7009/RPX2014)
Multiple dose of Carbavance
干预措施: RPX7009 and RPX2014 (Drug)
结局指标
主要结局
Pharmacokinetics from baseline through the end of the study
时间窗: 2 days
Assessment of plasma, ELF and AM concentrations of RPX2014 and RPX7009 after 3 doses of Carbavance
次要结局
- IV Carbavance concentrations in lung fluid(2 days)