A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Single and Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics of Oral QPX2015 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Peak plasma Concentration measurements by subject and by cohort (Cmax)
研究概览
简要总结
QPX2015 (beta-lactam antibiotic) is being studied at higher than approved doses to combine with a new beta-lactamase inhibitor 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 both hospital acquired and community acquired infections. In particular, the increase in Enterobacteriaceae expressing extended spectrum beta-lactamases (ESBLs) and carbapenemases that are resistant to all oral beta-lactams and fluoroquinolones in the community have resulted in many patients requiring admission just for IV antibiotics to treat their infections.
Qpex Biopharma is developing a fixed combination antibiotic of QPX2015 (beta-lactam antibiotic) plus a new beta-lactamase inhibitor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
double-blind, placebo controlled ascending single- and multiple-dose
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 of non-child bearing potential, 18 to 55 years of age (inclusive).
- •Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
- •Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, electrocardiograms [ECGs], physical examination) as assessed by the PI.
- •Voluntarily consent to participate in the study.
- •If male, agree to be sexually abstinent or agree to use two approved methods of contraception when engaging in sexual activity from study check-in through completion of the end-of-study. Subjects must agree to use two approved methods of contraception for 30 days following the last administration of the study drug, and to not donate sperm during this same period of time. In the event that the sexual partner is surgically sterile, contraception is not necessary.
- •Females of non-childbearing potential with serum FSH levels ≥ 40 mIU/mL are either postmenopausal (defined as 12 months spontaneous amenorrhea) or have undergone sterilization procedures at least 6 months prior to dosing.
排除标准
- •History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
- •Positive urine drug/alcohol testing at screening or check-in (Day -1).
- •Positive testing for HIV, hepatitis B or C
- •History or presence of alcoholism or drug abuse within last 2 years
- •Use of more than 5 packs/week of tobacco/nicotine-containing product within last 6 months prior dosing.
- •Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to dosing.
- •Use of any over-the-counter (OTC) medication, including herbal products and vitamins, within the 7 days prior to dosing.
- •Use of antacids, H2 receptor blockers or proton pump inhibitors 3 days prior to dosing.
- •History of any hypersensitivity or allergic reaction to cephalosporins, penicillins, carbapenems, or monobactams).
- •Participation in another investigational clinical trial within 30 days prior to Dosing or within 5 half-lives of the previous investigational drug, whichever is longer.
- •Females who are pregnant or lactating.
- •QTcF interval >450 msec, or history of prolonged QT syndrome at screening or check-in
- •Calculated creatinine clearance less than 80 mL/min (Cockcroft-Gault method) at screening or check-in.
- •Subjects who have any clinically significant abnormalities on laboratory values: White blood cell count < 3,000/mm3, hemoglobin < 11g/dL or Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm
- •Liver function abnormalities 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
QPX2015
QPX2015, antibiotic
干预措施: QPX2015 (Drug)
Placebo
Matched placebo
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Peak plasma Concentration measurements by subject and by cohort (Cmax)
时间窗: Study Day 1 to 13
Comparison will be performed between the cohorts for Cmax. Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed.
Area under the plasma concentration versus time curve (AUC) between cohorts
时间窗: Study Day 1 to 13
Comparison will be performed between the cohorts for AUC. Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed.
Urine PK % dose excreted by subject and by cohort
时间窗: Study Day 1 to 13
Urine PK parameters such as amount of % dose excreted will be calculated from urinary excretion data
Incidence of Treatment -Emergent Adverse events by subject and by cohort
时间窗: Study Day 1 to 13
Number of patients with Treatment-Emergent AEs by treatment arm, severity and relationship to treatment
Number of patients with changes from baseline in safety parameters
时间窗: Study Day 1 to 13
Number of patients with changes in safety parameters before and after dosing by subject and treatment arm
Time concentration data measurements by subject and by cohort (Tmax)
时间窗: Study Day 1 to 13
Comparison will be performed between the cohorts for Tmax.
Urine PK amount excreted by subject and by cohort
时间窗: Study Day 1 to 13
Urine PK parameters such as amount excreted will be calculated from urinary excretion data
次要结局
未报告次要终点