A Phase 1, Open-label, Single Oral Dose Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Cadazolid in Patients With Severe Clostridium Difficile Infection (CDI)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Maximum plasma concentration (Cmax) of cadazolid
研究概览
简要总结
The study investigated the pharmacokinetics, safety, and tolerability of cadazolid in subjects with severe Clostridium difficile diarrhea (CDAD) and whether this influenced the quantity of cadazolid absorbed into the systemic circulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 否
入选标准
- •Signed informed consent prior to any study-mandated procedure.
- •Non-pregnant females were to remain non-pregnant for 1 month after the end of the study. Female subjects of child-bearing potential must have had a negative serum pregnancy test at screening and must have used a reliable method of contraception
- •Subjects with severe CDAD; Clostridium difficile infection (CDI) must have been microbiologically proven, using a validated enzyme-linked immunosorbent assay (ELISA) for the detection of C. difficile toxin A (TcdA) and/or C. difficile toxin B (TcdB). The severity of CDAD was assessed according to the current European Union guidelines - European Society of Clinical Microbiology and Infectious Diseases (ESCMID).
- •Received oral vancomycin or oral/intravenous (i.v.) metronidazole therapy for the treatment of CDAD.
- •Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.
排除标准
- •Known hypersensitivity to any excipients of the drug formulation.
- •Clinical evidence of any relevant disease other than CDAD and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study drug.
- •Veins unsuitable for i.v. puncture on either arm (e.g., veins that are difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture).
- •Subjects with rare hereditary fructose intolerance, glucose-galactose malabsorption, saccharase-isomaltase deficiency or previously undiagnosed diabetes mellitus.
- •Subjects who have a life-threatening condition, which may be related to CDAD or other underlying illness.
- •Any clinically relevant electrocardiogram (ECG) abnormality at screening.
- •Subjects who were unable to swallow or have difficulty swallowing.
- •Subjects with vomiting, ileus or not passing stool.
- •Likelihood of death within 72 hours from any cause.
- •Life-threatening or fulminant CDAD (White blood cell count > 30 × 10^9/L; temperature > 40 °C; or septic shock, peritoneal signs or significant dehydration).
- •History of ulcerative colitis or Crohn's disease.
- •Loss of 250 mL or more of blood within 3 months prior to screening.
- •Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
- •Positive results from the human immunodeficiency virus (HIV) serology at screening.
- •Legal incapacity or limited legal capacity at screening.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
研究组 & 干预措施
Cadazolid
Single oral dose of 3000 mg.
干预措施: Cadazolid (Drug)
结局指标
主要结局
Maximum plasma concentration (Cmax) of cadazolid
时间窗: 144 hours
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing. Cmax was calculated on the basis of the blood sampling time points.
Time to reach maximum plasma concentration (tmax) of cadazolid
时间窗: 144 hours
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing. tmax was calculated on the basis of the blood sampling time points.
Area under the plasma concentration-time curve (AUC(0-144h)) of cadazolid
时间窗: 144 hours
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing. AUC(0-144) was calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification.
Unchanged cadazolid in urine up to Day 7
时间窗: 144 hours
Urine was collected into standard-weight polyethylene containers over the following time intervals: 0-12 h, 12-24 h, 24-36 h, 36-48 h, 48-72 h, 72-96 h, 96-120 h, and 120-144 h. The concentration of cadazolid was determined using validated liquid chromatography-tandem mass spectrometry assays. The amount of drug excreted in the urine was obtained by multiplying the concentration of drug by the volume of matrix collected.
Unchanged cadazolid in faeces up to Day 7
时间窗: 144 hours
Faeces were collected in pre-weighed polypropylene boxes. The concentration of cadazolid was determined using validated liquid chromatography-tandem mass spectrometry assays. The amount of drug excreted in the faeces was obtained by multiplying the concentration of drug by the volume of matrix collected.
次要结局
- Change from baseline up to Day 7 in systolic blood pressure (SBP)(144 hours)
- Change from baseline up to Day 7 in diastolic blood pressure (DBP)(144 hours)
- Change from baseline up to Day 7 in pulse rate(144 hours)
- Change from baseline to Day 7 in body weight(144 hours)
- Change from baseline up to Day 7 in heart rate(144 hours)
- Change from baseline up to Day 7 in PQ interval (time interval from the beginning of the P wave to the beginning of the QRS complex)(144 hours)
- Change from baseline up to Day 7 in QRS duration (time interval from the beginning of the Q wave to the end of the S wave)(144 hours)
- Change from baseline up to Day 7 in QT (time interval from beginning of the Q wave until end of the T wave)(144 hours)
- Change from baseline up to Day 7 in QT interval according to Bazett's correction (QTcB)(144 hours)
- Change from baseline up to Day 7 in QT interval according to Fridericia's correction (QTcF)(144 hours)
- Frequency of treatment-emergent ECG abnormalities from up to Day 7(144 hours)