A Prospective, Multicenter Study to Investigate the Pharmacokinetics, Safety, and Efficacy of Cadazolid Versus Vancomycin in Pediatric Subjects With Clostridium Difficile-associated Diarrhea
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 20
- 主要终点
- Maximal Plasma Concentration (Cmax) of Cadazolid During Part A
研究概览
简要总结
Cadazolid has demonstrated activity against a bacteria named Clostridium difficile in animal studies. The results of a first study conducted in adult patients have suggested efficacy of the new antibiotic, cadazolid, in the treatment of diarrhea caused by this bacteria. This is the first study of cadazolid in children. The overall purpose of this study is to provide reassurance on the safety and efficacy of cadazolid in children suffering from infection due to Clostridium difficile.
详细描述
This multicenter, study will be run into two parts. Both parts will be run in consecutive age cohorts, starting from the oldest age categories(12 to < 18 years old) to the youngest (birth to < 3 months).
- Part A is an open-label, dose finding part to be conducted in at least 24 subjects.
- Part B follows a randomized, assessor-blinded, parallel-group design with vancomycin used as an active comparator. Part B will be conducted in about 176 children.
In both parts, the treatment period will be 10 days and will be followed by a Follow-up period of 28-32 days.
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
- Single (Outcomes Assessor)
盲法说明
Assessor masking in Part B only (no masking in Part A)
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent by parents or legally authorized representatives (LAR) and assent by the child according to local requirements prior to initiation of any study-mandated procedure.
- •Male or female from birth to < 18 years of age, diagnosed with Clostridium Difficile-associated diarrhea (CDAD).
- •Females of childbearing potential must have a negative pregnancy test at screening and must agree to use an adequate and reliable method of contraception.
排除标准
- •Positive Rotavirus test for subjects < 5 years.
- •Fulminant or life-threatening CDAD.
- •More than one previous episode of CDAD in the 3 month period prior to enrollment / randomization.
- •Antimicrobial treatment active against CDAD administered within 24 h prior to screening except for metronidazole treatment failures (MTF).
- •Subjects with body weight < 3 kg.
- •Inflammatory bowel disease, chronic abdominal pain, or chronic diarrhea of any etiology.
- •Fecal microbiota transplant (FMT), immunoglobulin therapy, or any investigational drug to prevent or treat CDAD within 1 month period (or 5 half-lives in case of investigational drug, whichever is longer) prior to enrollment / randomization.
- •Monoclonal antibodies against C. difficile within 6 months prior to enrollment / randomization.
- •Previous vaccination against C. difficile.
- •Known mental disorders.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study, or compliance with the protocol.
研究组 & 干预措施
Part A / Cohort A
Subjects from 12 years to 18 years old (exclusive) will receive cadazolid 500 mg per day for 10 days. The dose may be adjusted based on the pharmacokinetic (PK) and safety data reviewed for the first 3 subjects.
干预措施: Cadazolid (Drug)
Part A / Cohort B
Subjects from 6 years to 12 years old (exclusive) will receive cadazolid for 10 days. The dose will depend on the PK and safety data from cohort A reviewed by the Independent Data Monitoring Committee (IDMC).
干预措施: Cadazolid (Drug)
Part A / Cohort C
Subjects from 2 years to 6 years old (exclusive) will receive cadazolid for 10 days. The dose will depend on the PK and safety data from cohort B reviewed by the IDMC.
干预措施: Cadazolid (Drug)
Part A/ Cohort D
Subjects from 3 months to 2 years old (exclusive) will receive cadazolid for 10 days. The dose will depend on the PK and safety data from cohort C reviewed by the IDMC.
干预措施: Cadazolid (Drug)
Part A/ Cohort E
Subjects from birth to 3 months old (exclusive) will receive cadazolid for 10 days. The dose will depend on the PK and safety data from cohort D reviewed by the IDMC.
干预措施: Cadazolid (Drug)
Part B / Cadazolid
Subjects from birth to 18 years old (exclusive) will receive cadazolid for 10 days, at the dose defined in the corresponding age cohort in Part A.
干预措施: Cadazolid (Drug)
Part B / Vancomycin
Subjects from birth to 18 years old (exclusive) will receive vancomycin capsule (for subjects able to swallow) or vancomycin solution (for the others) during 10 days .
干预措施: Vancomycin capsule (Drug)
Part B / Vancomycin
Subjects from birth to 18 years old (exclusive) will receive vancomycin capsule (for subjects able to swallow) or vancomycin solution (for the others) during 10 days .
干预措施: Vancomycin solution (Drug)
结局指标
主要结局
Maximal Plasma Concentration (Cmax) of Cadazolid During Part A
时间窗: Day 10 (End of Treatment)
Blood samples are collected at different timepoints on Day 10 for the determination of cadazolid Cmax after 10 days of treatment.
Area Under the Plasma Concentration Time Curve (AUC) of Cadazolid During Part A
时间窗: Day 10 (End of Treatment)
Blood samples are collected at different timepoints for the determination of the cadazolid AUC over one dosing interval (0-12h) on Day 10.
Time to Reach Cmax (Tmax) of Cadazolid During Part A
时间窗: Day 10 (End of Treatment)
Blood samples are collected at different timepoints to determine the time when the maximal plasma concentration of cadazolid is reached.
Fecal Concentrations of Cadazolid During Part A
时间窗: Day 10 (End of Treatment)
A fecal sample is collected as the end-of-treatment visit in all participants in Part A.
Clinical Cure Rate During Part B
时间窗: Day 10 (End of Treatment) + 2 days
This is the percentage of participants in part B reported as with a clinical cure. Clinical Cure is defined as: • \<3 unformed bowel movement (UBM) per day (or no water diarrhea if subjects \< 2 years of age), for at least 2 consecutive days between first dose of study treatment up to end of treatment (EOT) (inclusive) AND • Subject remains well up to EOT + 2 days (inclusive) based on investigator judgment AND • No need for additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) between first dose of study treatment up to EOT + 2 days (inclusive). percentage of subjects with a clinical cure
次要结局
- Clinical Cure Rate During Part A(Day 10 (End of Treatment) + 2 days)
- Adverse Events Leading to Premature Discontinuation of Study Treatment(Up to Day 10)
- Time to Recurrence in Part B(Day 40 (on average))
- Sustained Clinical Cure Rate During Part A and Part B(Day 40 (on average))
- Marked Abnormalities in Vital Signs(Day 17 (on average))
- Treatment-emergent Adverse Events (TEAES)(Day 17 (on average))
- Recurrence Rate During Part A and Part B(Day 40 (on average))
- Time to Resolution of Diarrhea in Part B(Day 10)
- Marked Abnormalities in Clinical Laboratory Parameters(Day 17 (on average))