A Phase 1, Open-label, Single-dose Study to Determine the Safety and Pharmacokinetics of Carbavance™ (RPX2014/RPX7009) in Subjects With Renal Insufficiency
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Safety 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 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 safety, tolerability and pharmacokinetics of intravenous RPX2014 and RPX7009, administered in combination in subjects with varying degrees of renal insufficiency.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females aged 18 through 80 years of age
- •Willing to abstain from alcohol for 48 hours prior to dosing through discharge
- •Normal volunteer first matched by age (± 10 years), BMI (± 20%), and gender to the mean values of the moderate renal insufficiency group.
- •Have negative test results for HBsAg, anti-HCV antibody and anti-HIV antibody.
- •Voluntarily consent to participate in the study
- •Sexually abstinent or agree to use two approved methods of contraception.
- •Assessment of renal insufficiency for assignment to study groups will be based on measurements of eGFR calculated by the MDRD equation at the Screening Visit to determine eligibility.
排除标准
- •Unstable or new medical conditions (e.g., cardiovascular, respiratory, hepatic, renal, gastrointestinal, autoimmune, endocrine, or neurological disorders)
- •Hypersensitivity or idiosyncratic reaction to β-lactam antibiotics (e.g. penicillins, cephalosporins, or carbapenems)
- •History of clinically significant seizures, head injury, or meningitis.
- •Current evidence or history of malignancy, excluding basal cell carcinoma, in the 2 years prior to Day -1 with no evidence of recurrence.
- •Females who are pregnant, lactating, or have a positive pregnancy test
- •Previously received any dose of Carbavance (RPX2014/RPX7009).
- •Current participation in another investigational study or participation in another investigational clinical study within 30 days prior to the Screening Visit.
- •Blood donation or significant blood loss (i.e., > 500 mL) within 56 days prior to Day
- •Plasma or platelet donation within 14 days prior to Day -
- •Any acute illness requiring antibiotic drug therapy within 30 days prior to Day 1 or a febrile illness within 7 days prior to Day
- •Vigorous exercise from 48 hours prior to Day -1 until the day of discharge from the study.
- •Positive urine drug/alcohol test at the Screening Visit or Day -1
- •Concurrent use of medications known to affect the elimination of serum creatinine (e.g., trimethoprim/sulfamethoxazole [Bactrim®] or cimetidine [Tagamet®]) and competitors of renal tubular secretion (e.g., probenecid) within 30 days prior to the first dose of study drug
- •Abnormal and clinically significant findings on physical examination, medical history, serum chemistry, hematology, or urinalysis
- •Use of any other prescription or nonprescription drugs, vitamins, grapefruit/grapefruit juice or dietary or herbal supplements within 14 days prior to Day -
- •Oral contraceptives are permitted for birth control.
- •Acetaminophen (≤ 1 g/day) and low-dose ASA (i.e., ≤ 325 mg per day) are permitted.
- •Currently receives hemodialysis or peritoneal dialysis.
研究组 & 干预措施
Single dose of RPX7009 and RPX2014
Single dose of combination RPX7009 and RPX2014
干预措施: RPX7009 and RPX2014 (Drug)
结局指标
主要结局
Safety from baseline through the end of the study
时间窗: 7days
Number of patients with adverse events; assessed by patient reporting, collection of vital signs, ECGs and absolute values and changes over time of hematology, chemistry and urinalysis
次要结局
未报告次要终点