A Phase 3, Multicenter, Investigator-blind, Randomized, Parallel Group Study to Investigate the Safety and Efficacy of Fidaxomicin Oral Suspension or Tablets Taken q12h, and Vancomycin Oral Liquid or Capsules Taken q6h, for 10 Days in Pediatric Subjects With Clostridium Difficile-associated Diarrhea
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 44
- 主要终点
- Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days
研究概览
简要总结
The purpose of this study was to investigate the clinical response to fidaxomicin oral suspension or tablets and vancomycin oral liquid or capsules in pediatric participants with Clostridium difficile-associated diarrhea (CDAD). It also investigated the recurrence/sustained clinical response to and safety of fidaxomicin and vancomycin, as well as acceptance of the fidaxomicin oral suspension formulation.
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 (Investigator)
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is diagnosed with CDAD according to local diagnostic criteria. As a minimum there must be positive detection, within 72 hours prior to randomization, of either toxin A and/or toxin B in stool or positive detection of toxigenic C. difficile in stool and:
- •Subject from Birth to < 2 years: watery diarrhea in the 24 hours prior to screening.
- •Subject ≥ 2 years to < 18 years: ≥ 3 unformed bowel movements in the 24 hours prior to screening.
- •Male and female subjects aged from birth to < 18 years: Note that in the United States of America subjects can only be included if aged ≥ 6 months to < 18 years.
- •For subjects < 5 years: Negative rotavirus test.
- •Female subject of childbearing potential:
- •must have a negative urine pregnancy test at Screening, and
- •must abstain from sexual activity for the duration of the study, or
- •must use two forms of birth control (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days after the final study drug administration.
- •Female subject must not be breastfeeding at Screening or during the study period, and for 28 days after the final study drug administration.
- •Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.
- •Subject agrees not to participate in another interventional study while in the study (with the exception of studies as described in exclusion criteria below).
排除标准
- •Concurrent use of metronidazole, oral vancomycin or any other antibiotic treatments for CDAD. If the investigator feels the clinical imperative is to begin treatment before knowing the laboratory result for toxigenic C. difficile, up to four doses but no more than 24 hours of treatment with metronidazole, oral vancomycin or any other effective treatment for CDAD are allowed.
- •Subject has pseudomembranous colitis, fulminant colitis, toxic megacolon or ileus.
- •Subject has a history of inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease etc.).
- •Subject has diarrhea caused by an agent other than C. difficile (e.g. infections, infestations, drugs etc.).
- •Subject has known hypersensitivity to fidaxomicin, vancomycin or their excipients or to teicoplanin.
- •Subject has received an investigational therapy within 28 days, prior to Screening, with the exception of studies with primary treatment for cancer without novel Investigational Medicinal Product (IMP) and which do not affect the assessment of diarrhea.
研究组 & 干预措施
Fidaxomicin
Participants from birth to < 6 years of age received weight based doses of fidaxomicin oral suspension (32 mg/kg/day with a maximum dose of 400 mg/day divided in 2 doses) 2 times daily for 10 days. Participants aged ≥ 6 years to < 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
干预措施: Fidaxomicin oral suspension (Drug)
Fidaxomicin
Participants from birth to < 6 years of age received weight based doses of fidaxomicin oral suspension (32 mg/kg/day with a maximum dose of 400 mg/day divided in 2 doses) 2 times daily for 10 days. Participants aged ≥ 6 years to < 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
干预措施: Fidaxomicin tablets (Drug)
Vancomycin
Participants from birth to < 6 years of age received weight based doses of vancomycin oral liquid (40 mg/kg/day with a maximum dose of 500 mg/day divided in 4 doses) 4 times daily for 10 days. Participants aged ≥ 6 years to < 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days.
干预措施: Vancomycin oral liquid (Drug)
Vancomycin
Participants from birth to < 6 years of age received weight based doses of vancomycin oral liquid (40 mg/kg/day with a maximum dose of 500 mg/day divided in 4 doses) 4 times daily for 10 days. Participants aged ≥ 6 years to < 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days.
干预措施: Vancomycin capsules (Drug)
结局指标
主要结局
Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days
时间窗: Up to day 12
Initial clinical response (ICR) for ages from birth to \< 2 years was defined as absence of watery diarrhea for 2 consecutive treatment days, remaining well until study drug discontinuation. ICR for ages ≥ 2 years to \< 18 years was defined as improvement in number and character of bowel movements as determined by \< 3 unformed bowel movements (UBMs) per day for 2 consecutive treatment days, remaining well until study drug discontinuation. CCR was defined for both age groups as not requiring further CDAD therapy within 2 days after study drug completion, and was reported with a positive (Yes) or negative (No) outcome. Resolution of diarrhea was assessed during interviews of participant/parent/legal guardian, supplemented by review of personal records (if hospitalized) and checked for presence of watery diarrhea (ages from birth to \< 2 years) or number of UBMs (for ages ≥ 2 years to \< 18 years).
次要结局
- Percentage of Participants With Sustained Clinical Response (SCR) at EOT +9 Days(Up to day 19)
- Percentage of Participants With Global Cure (GC) at EOT +9 Days(Up to day 19)
- Percentage of Participants With Recurrence of CDAD at EOT +9 Days(Up to day 19)
- Percentage of Participants With SCR at EOT +16 Days(Up to day 26)
- Percentage of Participants With GC at EOT +16 Days(Up to day 26)
- Percentage of Participants With Recurrence of CDAD at EOT +16 Days(Up to day 26)
- Percentage of Participants With SCR at EOT +23 Days(Up to day 33)
- Percentage of Participants With GC at EOT +23 Days(Up to day 33)
- Percentage of Participants With Recurrence of CDAD at EOT +23 Days(Up to day 33)
- Percentage of Participants With SCR at End of Study (EOS) (EOT +30 Days)(Up to day 40)
- Percentage of Participants With GC at EOS (EOT +30 Days)(Up to day 40)
- Percentage of Participants With Recurrence of CDAD at EOS (EOT +30 Days)(Up to day 40)
- Time to Resolution of Diarrhea (TTROD)(Up to day 10)
- Time to Recurrence of CDAD for Participants With CCR at EOT +2 Days(Up to day 40)
- Number of Participants With Adverse Events (AEs)(From the first dose of study drug administration up to 30 days after EOT (up to day 40))
- Plasma Concentrations of Fidaxomicin(Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10)
- Plasma Concentrations of Metabolite OP-1118(Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10)
- Metabolite-to-Parent Ratio (MPRconc)(Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10)
- Fecal Concentrations of Fidaxomicin(Within 24 hours of a dose taken between day 5 and day 10)
- Fecal Concentrations of Metabolite OP-1118(Within 24 hours of a dose taken between day 5 and day 10)
- MPRconc Within 24 Hours of a Dose(Within 24 hours of a dose taken between day 5 and day 10)
- Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7(Days 1 and 7)