Evaluating Celecoxib Activity in Mycobacterium Tuberculosis: A Whole Blood Bactericidal Activity Study in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Log change CFU.day (cumulative over 8 hours) calculated from Mycobacteria Growth Indicator Tube (MGIT) Time to Positivity
研究概览
简要总结
The purpose of this study is to evaluate the bactericidal activity against Mycobacterium tuberculosis of celecoxib in combination with established drugs used to treat tuberculosis (TB). Pharmacokinetics (PK) and whole blood bactericidal activity (WBA) will be measured in healthy volunteers following administration of the study drugs alone and in combination.
详细描述
The whole blood bactericidal activity (WBA) assay is an ex vivo model for measuring the combined effects of administered drugs, host factors and strain factors on mycobacterial sterilisation. If performed in parallel with PK measurements, the method can be used to evaluate the effect of drugs throughout the dosing cycle. Celecoxib is a COX-2 inhibitor with immuno-modulatory properties important in the host defence against tuberculosis (TB). The aim of this trial is to investigate the effect on WBA of manipulation of the host response to TB using celecoxib, in combination with established TB drugs.
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
- None
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged over 21 years and below 60 years old
- •Male or female willing to comply with the study visits and procedures
- •Willing and able to provide written informed consent
排除标准
- •Women who are currently pregnant or breastfeeding
- •Body weight below 50kg
- •Clinical signs of active TB in the opinion of the investigator
- •Previous hypersensitivity, intolerance or allergy to rifampicin, pyrazinamide, COX-2 inhibitors, non-steroidal anti-inflammatory drugs or sulfonamides
- •Current use of any drugs or medication known to have an interaction with rifampicin, pyrazinamide or celecoxib
- •Current use or use in the last 2 weeks of non-steroidal anti-inflammatory drugs or COX-2 inhibitors
- •Current use or use in the last 2 weeks of any drugs, over the counter or herbal preparations that are known or potential inhibitors or inducers of cytochrome P450 enzymes
- •Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations
- •Known hepatic disease, recent hepatitis (within last 6 months) or alcohol abuse
- •Known cardiovascular disease, heart failure, stroke or current cardiovascular risk factors
- •Known peptic ulcer disease, previous gastrointestinal bleed or current risk factors for gastrointestinal events
- •Acute or previous gout, acute porphyria
- •Any other significant condition that would, in the opinion of the investigator, compromise the volunteer's safety or outcome in the trial
- •Current participation in other clinical intervention trial or research protocol
研究组 & 干预措施
Celecoxib plus rifampicin group
Visit 1: Celecoxib 400mg Visit 2: Rifampicin 10mg/kg Visit 3: Celecoxib 400mg PLUS rifampicin 10mg/kg
干预措施: Celecoxib (Drug)
Celecoxib plus rifampicin group
Visit 1: Celecoxib 400mg Visit 2: Rifampicin 10mg/kg Visit 3: Celecoxib 400mg PLUS rifampicin 10mg/kg
干预措施: Rifampicin (Drug)
Celecoxib plus pyrazinamide group
Visit 1: Celecoxib 400mg Visit 2: Pyrazinamide 25mg/kg Visit 3: Celecoxib 400mg PLUS pyrazinamide 25mg/kg
干预措施: Celecoxib (Drug)
Celecoxib plus pyrazinamide group
Visit 1: Celecoxib 400mg Visit 2: Pyrazinamide 25mg/kg Visit 3: Celecoxib 400mg PLUS pyrazinamide 25mg/kg
干预措施: Pyrazinamide (Drug)
结局指标
主要结局
Log change CFU.day (cumulative over 8 hours) calculated from Mycobacteria Growth Indicator Tube (MGIT) Time to Positivity
时间窗: 8 hours
Cumulative whole blood bactericidal activity (WBA)
次要结局
- Plasma concentrations of study drugs to determine the Maximum Plasma Concentration (Cmax)(8 hours)
- Plasma concentrations of study drugs to determine the Area Under the Curve (AUC)(8 hours)