Clinical Trial Results:
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
Summary
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EudraCT number |
2013-000508-40 |
Trial protocol |
DE BE SK PL IT ES HU FR |
Global end of trial date |
07 Mar 2018
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Results information
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Results version number |
v2(current) |
This version publication date |
18 Jun 2020
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First version publication date |
15 Sep 2018
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Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2819-CL-0202
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02218372 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Acronym: SUNSHINE | ||
Sponsors
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Sponsor organisation name |
Astellas Pharma Europe B.V.
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Sponsor organisation address |
Sylviusweg 62, Leiden, Netherlands, 2333 BE
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Public contact |
Clinical Trial Disclosure, Astellas Pharma Europe B.V., astellas.resultsdisclosure@astellas.com
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Scientific contact |
Clinical Trial Disclosure, Astellas Pharma Europe B.V., astellas.resultsdisclosure@astellas.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000636-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Mar 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Mar 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to investigate the clinical response to fidaxomicin granules for oral suspension or tablets and vancomycin oral liquid or capsules of pediatric participants with Clostridium Difficile-Associated Diarrhea (CDAD) from birth to < 18 years of age.
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Protection of trial subjects |
This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Good Clinical Practice (GCP) Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Jan 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 7
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
France: 11
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Country: Number of subjects enrolled |
Germany: 5
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Country: Number of subjects enrolled |
Hungary: 17
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Country: Number of subjects enrolled |
Italy: 8
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Country: Number of subjects enrolled |
Poland: 14
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Country: Number of subjects enrolled |
Romania: 9
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Country: Number of subjects enrolled |
Spain: 19
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Country: Number of subjects enrolled |
United States: 57
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Worldwide total number of subjects |
148
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EEA total number of subjects |
90
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
30
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Children (2-11 years) |
89
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Adolescents (12-17 years) |
29
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Pediatric participants with clostridium difficile-associated diarrhea (CDAD) were enrolled in this multicenter study. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Eligible participants who met inclusion criteria and none of the exclusion criteria were enrolled, 159 participants were assessed for eligibility of whom 148 were randomized. Participants were randomized to either fidaxomicin or vancomycin in a 2:1 ratio, stratified by age group. | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||||||||||||||||||||
Roles blinded |
Investigator [1] | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Fidaxomicin | |||||||||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Fidaxomicin oral suspension
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
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.
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Investigational medicinal product name |
Fidaxomicin tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants aged ≥ 6 years to < 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
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Arm title
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Vancomycin | |||||||||||||||||||||||||||
Arm description |
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. | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Vancomycin oral liquid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral liquid
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Routes of administration |
Oral use
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Dosage and administration details |
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.
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Investigational medicinal product name |
Vancomycin capsules
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Participants aged ≥ 6 years to < 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days.
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Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Double blinding of the study drug for this pediatric study population was not feasible, given dosing constraints, the study was investigator-blinded only. |
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Baseline characteristics reporting groups
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Reporting group title |
Fidaxomicin
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vancomycin
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Fidaxomicin
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Reporting group description |
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. | ||
Reporting group title |
Vancomycin
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Reporting group description |
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. | ||
Subject analysis set title |
Fidaxomin all formulations
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants received either fidaxomicin oral suspension or tablet formulation.
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Subject analysis set title |
Fidaxomicin oral suspension
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants received fidaxomicin oral suspension formulation.
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Subject analysis set title |
Fidaxomicin tablets
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants received fidaxomicin tablets formulation.
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Subject analysis set title |
Vancomycin oral liquid
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants received vancomycin oral liquid formulation.
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Subject analysis set title |
Full Analysis Set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The FAS consisted of all randomized participants who received at least 1 dose of study drug. In the FAS, participants were allocated to the treatment arm corresponding to the study medication that the participant was randomized to (treatment allocation as randomized).
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Subject analysis set title |
Safety Analysis Set (SAF)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The SAF consisted of all randomized participants who received at least 1 study drug dose. In the SAF, participants were allocated to the treatment arm corresponding to study drug first administered (fidaxomicin or vancomycin), even if it differed from the treatment randomized to.
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End point title |
Percentage of Participants with Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days | ||||||||||||
End point description |
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). The analysis population consisted of the FAS.
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End point type |
Primary
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End point timeframe |
Up to day 12
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Statistical analysis title |
Adjusted Difference of CCR at EOT + 2 Days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified Cochran-Mantel-Haenszel (CMH) method. Newcombe 95% confidence intervals (CIs) presented for adjusted treatment difference.
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Comparison groups |
Fidaxomicin v Vancomycin
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Number of subjects included in analysis |
142
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
7.5
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-7.4 | ||||||||||||
upper limit |
23.9 |
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End point title |
Percentage of Participants with Sustained Clinical Response (SCR) at EOT +9 Days | ||||||||||||
End point description |
SCR at EOT + 9 days was defined as CCR (EOT + 2 days) without CDAD recurrence until assessment at EOT +9 days during the follow-up period. Recurrence for ages from birth to < 2 years was defined as re-establishment of watery diarrhea after CCR to an extent that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic Clostridium difficile (C. difficile) in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. Recurrence for ages ≥ 2 years < 18 years was defined as re-establishment of diarrhea after CCR to an extent (as measured by the frequency of UBMs) that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. FAS population (participants with CCR at EOT +2 days).
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End point type |
Secondary
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End point timeframe |
Up to day 19
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Statistical analysis title |
Adjusted Difference of SCR at EOT +9 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
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Comparison groups |
Fidaxomicin v Vancomycin
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
16.3
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.8 | ||||||||||||
upper limit |
34.2 |
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End point title |
Percentage of Participants with Global Cure (GC) at EOT +9 Days | ||||||||||||
End point description |
GC was reported as a positive (Yes) or negative (No) outcome and was calculated using SCR and ICR/CCR values according to the following conditions: ● if ICR/CCR=Yes and SCR=Yes, then Global Cure was Yes. ● if ICR/CCR=Yes and SCR =No, then Global Cure was No. ● if ICR/CCR=No (SCR not assessed), then Global Cure was No. ● if ICR/CCR=Missing (SCR not assessed), then Global Cure was set to No. No multiple imputation method (MI) was used for global cure at EOT + 9 days. The analysis population consisted of the FAS.
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End point type |
Secondary
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End point timeframe |
Up to day 19
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Statistical analysis title |
Adjusted Difference of GC at EOT +9 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of rates was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
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Comparison groups |
Fidaxomicin v Vancomycin
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Number of subjects included in analysis |
142
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
21.3
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
4.5 | ||||||||||||
upper limit |
37.7 |
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End point title |
Percentage of Participants with Recurrence of CDAD at EOT +9 Days | ||||||||||||
End point description |
Recurrence for ages from birth to < 2 years was defined as re-establishment of watery diarrhea after CCR to an extent that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. Recurrence for ages ≥ 2 years < 18 years was defined as re-establishment of diarrhea after CCR to an extent (as measured by the frequency of UBMs) that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. The analysis population consisted of the FAS (participants with CCR at EOT +2 days).
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End point type |
Secondary
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End point timeframe |
Up to day 19
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Statistical analysis title |
Adjusted Diff. of CDAD Recurrence at EOT +9 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
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Comparison groups |
Fidaxomicin v Vancomycin
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
-16.3
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-34.2 | ||||||||||||
upper limit |
-1.8 |
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End point title |
Percentage of Participants with SCR at EOT +16 Days | ||||||||||||
End point description |
SCR at EOT + 16 days was defined as CCR (EOT + 2 days) without CDAD recurrence until assessment at EOT + 16 days during the follow-up period. Recurrence for ages from birth to < 2 years was defined as re-establishment of watery diarrhea after CCR to an extent that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. Recurrence for ages ≥ 2 years < 18 years was defined as re-establishment of diarrhea after CCR to an extent (as measured by the frequency of UBMs) that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. The analysis population consisted of the FAS (participants with CCR at EOT +2 days).
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End point type |
Secondary
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End point timeframe |
Up to day 26
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Statistical analysis title |
Adjusted Difference of SCR at EOT +16 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
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Comparison groups |
Fidaxomicin v Vancomycin
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
17.2
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.9 | ||||||||||||
upper limit |
35.6 |
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End point title |
Percentage of Participants with GC at EOT +16 Days | ||||||||||||
End point description |
GC was reported as a positive (Yes) or negative (No) outcome and was calculated using SCR and ICR/CCR values according to the following conditions: ● if ICR/CCR=Yes and SCR=Yes, then Global Cure was Yes. ● if ICR/CCR=Yes and SCR =No, then Global Cure was No. ● if ICR/CCR=No (SCR not assessed), then Global Cure was No. ● if ICR/CCR=Missing (SCR not assessed), then Global Cure was set to No. No multiple imputation method (MI) was used for global cure at EOT + 16 days. The analysis population consisted of the FAS.
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End point type |
Secondary
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End point timeframe |
Up to day 26
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Statistical analysis title |
Adjusted Difference of GC at EOT +16 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of rates was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
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Comparison groups |
Fidaxomicin v Vancomycin
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Number of subjects included in analysis |
142
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
19.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.3 | ||||||||||||
upper limit |
35.9 |
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End point title |
Percentage of Participants with Recurrence of CDAD at EOT +16 Days | ||||||||||||
End point description |
Recurrence for ages from birth to < 2 years was defined as re-establishment of watery diarrhea after CCR to an extent that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. Recurrence for ages ≥ 2 years < 18 years was defined as re-establishment of diarrhea after CCR to an extent (as measured by the frequency of UBMs) that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. The analysis population consisted of the FAS (participants with CCR at EOT +2 days).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 26
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Diff. of CDAD Recurrence at EOT +16 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
|
||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
-17.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-35.6 | ||||||||||||
upper limit |
-1.9 |
|
|||||||||||||
End point title |
Percentage of Participants with SCR at EOT +23 Days | ||||||||||||
End point description |
SCR at EOT + 23 days was defined as CCR (EOT + 2 days) without CDAD recurrence until assessment at EOT + 16 days during the follow-up period. Recurrence for ages from birth to < 2 years was defined as re-establishment of watery diarrhea after CCR to an extent that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. Recurrence for ages ≥ 2 years < 18 years was defined as re-establishment of diarrhea after CCR to an extent (as measured by the frequency of UBMs) that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. The analysis population consisted of the FAS (participants with CCR at EOT +2 days).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 33
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Difference of SCR at EOT +23 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
|
||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
15.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.5 | ||||||||||||
upper limit |
34.5 |
|
|||||||||||||
End point title |
Percentage of Participants with GC at EOT +23 Days | ||||||||||||
End point description |
GC was reported as a positive (Yes) or negative (No) outcome and was calculated using SCR and ICR/CCR values according to the following conditions: ● if ICR/CCR=Yes and SCR=Yes, then Global Cure was Yes. ● if ICR/CCR=Yes and SCR =No, then Global Cure was No. ● if ICR/CCR=No (SCR not assessed), then Global Cure was No. ● if ICR/CCR=Missing (SCR not assessed), then Global Cure was set to No. No multiple imputation method (MI) was used for global cure at EOT + 23 days. The analysis population consisted of the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 33
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Difference of GC at EOT +23 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of rates was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
|
||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
142
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
18.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.5 | ||||||||||||
upper limit |
35.3 |
|
|||||||||||||
End point title |
Percentage of Participants with Recurrence of CDAD at EOT +23 Days | ||||||||||||
End point description |
Recurrence for ages from birth to < 2 years was defined as re-establishment of watery diarrhea after CCR to an extent that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. Recurrence for ages ≥ 2 years < 18 years was defined as re-establishment of diarrhea after CCR to an extent (as measured by the frequency of UBMs) that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. The analysis population consisted of the FAS (participants with CCR at EOT +2 days).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 33
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Diff. of CDAD Recurrence at EOT +23 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
|
||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
-15.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-34.5 | ||||||||||||
upper limit |
0.5 |
|
|||||||||||||
End point title |
Percentage of Participants with SCR at End of Study (EOS) (EOT +30 Days) | ||||||||||||
End point description |
SCR at EOS was defined as CCR (EOT + 2 days) without CDAD recurrence until assessment at EOS (EOT + 30 days) during the follow-up period. Recurrence for ages from birth to < 2 years was defined as re-establishment of watery diarrhea after CCR to an extent that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. Recurrence for ages ≥ 2 years < 18 years was defined as re-establishment of diarrhea after CCR to an extent (as measured by the frequency of UBMs) that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. The analysis population consisted of the FAS (participants with CCR at EOT +2 days).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 40
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Difference of SCR at EOS (EOT +30 days) | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
|
||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
15.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.5 | ||||||||||||
upper limit |
34.5 |
|
|||||||||||||
End point title |
Percentage of Participants with GC at EOS (EOT +30 Days) | ||||||||||||
End point description |
GC was reported as a positive (Yes) or negative (No) outcome and was calculated using SCR and ICR/CCR values according to the following conditions: ● if ICR/CCR=Yes and SCR=Yes, then Global Cure was Yes. ● if ICR/CCR=Yes and SCR =No, then Global Cure was No. ● if ICR/CCR=No (SCR not assessed), then Global Cure was No. ● if ICR/CCR=Missing (SCR not assessed), then Global Cure was set to No. Global Cure at EOT +30 days was derived using MI in case ICR/CCR=Missing (SCR not assessed) following Rubin’s multiple imputation method. The analysis population consisted of the FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 40
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted Difference of GC at EOS (EOT +30 days) | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of rates was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
|
||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
142
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
18.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.5 | ||||||||||||
upper limit |
35.3 |
|
|||||||||||||
End point title |
Percentage of Participants with Recurrence of CDAD at EOS (EOT +30 Days) | ||||||||||||
End point description |
Recurrence for ages from birth to < 2 years was defined as re-establishment of watery diarrhea after CCR to an extent that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. Recurrence for ages ≥ 2 years < 18 years was defined as re-establishment of diarrhea after CCR to an extent (as measured by the frequency of UBMs) that was greater than that noted on the last day of study drug with positive direct or indirect testing for the presence of toxigenic C. difficile in stool and that, in the investigator's opinion, required retreatment with CDAD anti-infective therapy. The analysis population consisted of the FAS (participants with CCR at EOT +2 days).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 40
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adj. Diff. of CDAD Recurrence at EOS/EOT +30 days | ||||||||||||
Statistical analysis description |
Adjusted treatment difference of proportions was calculated using a stratified CMH method. Newcombe 95% CIs presented for adjusted treatment difference.
|
||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
adjusted treatment difference | ||||||||||||
Point estimate |
-15.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-34.5 | ||||||||||||
upper limit |
0.5 |
|
|||||||||||||
End point title |
Time to Resolution of Diarrhea (TTROD) | ||||||||||||
End point description |
TTROD for ages from birth < 2 years was defined as time elapsing (hours rounded up from minutes > 30) from treatment start (time of first study drug dose) to diarrhea resolution (time of last episode of watery diarrhea the day prior to the first of 2 consecutive days without watery diarrhea sustained through EOT). TTROD for ages ≥ 2 years to < 18 years was defined as time elapsing (hours rounded up from minutes > 30) from treatment start (time of first dose) to diarrhea resolution (time of the last UBM the day prior to the first of 2 consecutive days of < 3 UBMs sustained through EOT). TTROD by Kaplan-Meier Method. Those who completed treatment but did not show diarrhea resolution until EOT were censored at Day 10/240 hours. Those who did not complete treatment, discontinued earlier but did not show diarrhea resolution until disc. day were censored at disc. (days converted to hours). Those whose diarrhea did not continue after first dose were included with a TTROD of 1 hour. FAS.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 10
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Time to resolution of diarrhea | ||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
142
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.579 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Time to Recurrence of CDAD for Participants with CCR at EOT +2 Days | ||||||||||||
End point description |
Time to recurrence was defined as the time (days) from CCR until the onset of recurrence. Time to recurrence of CDAD by Kaplan-Meier Method. Data for median was estimated and the 95% CI could not be estimated due to low event rate. Data not evaluable denoted as "99999." Although median time was evaluable (25 days for the fidaxomicin arm and 26 days for the vancomycin arm) "99999" was entered to bypass system validation error, since 95% CI was not evaluable and system requires "99999" to be entered for data not available (the median values are not between the low and high values of "99999". The analysis population consisted of the FAS (participants with CCR at EOT +2 days). Participants with CCR at EOT+2 days, who completed the follow-up period but did not experience a recurrence of CDAD were censored at EOT+30 days and those who did not complete the follow-up period and discontinued during this period and did not experience a recurrence of CDAD were censored at day of discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to day 40
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Time to recurrence of CDAD | ||||||||||||
Comparison groups |
Fidaxomicin v Vancomycin
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.023 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants with Adverse Events (AEs) | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug or who had undergone study procedures which did not necessarily have a causal relationship with this treatment. This included abnormal laboratory tests, vital signs, electrocardiogram data or physical examinations that were defined as AEs if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant in the investigator's opinion. The following standard with 3 grades was used to measure the severity of AEs, including abnormal clinical laboratory values: ● Mild: No disruption of normal daily activities ● Moderate: Affected normal daily activities ● Severe: Inability to perform daily activities. A treatment-emergent adverse event (TEAE) was defined as an AE observed after starting administration of the test drug/comparative drug. The analysis population consisted of the SAF.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From the first dose of study drug administration up to 30 days after EOT (up to day 40)
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Plasma Concentrations of Fidaxomicin | ||||||||||||||||||||||||
End point description |
Drug concentration was derived from the blood samples collected. The analysis population consisted of the pharmacokinetics analysis set (PKAS). The PKAS consisted of all participants randomized to fidaxomicin, having received at least 1 dose of fidaxomicin and having at least 1 valid measurement of plasma concentration or fecal concentration of fidaxomicin or its main metabolite OP-1118. N is the number of participants with available data at each time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Plasma Concentrations of Metabolite OP-1118 | ||||||||||||||||||||||||
End point description |
Drug concentration was derived from the blood samples collected. The analysis population consisted of the PKAS. N is the number of participants with available data at each time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Metabolite-to-Parent Ratio (MPRconc) | ||||||||||||||||||||||||
End point description |
Drug concentration was derived from the blood samples collected. The analysis population consisted of the PKAS. N is the number of participants with available data at each time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Fecal Concentrations of Fidaxomicin | ||||||||||||||||||||
End point description |
Drug concentration was derived from the stool samples collected. The analysis population consisted of the PKAS.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Within 24 hours of a dose taken between day 5 and day 10
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Fecal Concentrations of Metabolite OP-1118 | ||||||||||||||||
End point description |
Drug concentration was derived from the stool samples collected. The analysis population consisted of the PKAS.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Within 24 hours of a dose taken between day 5 and day 10
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
MPRconc Within 24 Hours of a Dose | ||||||||||||||||||||
End point description |
Drug concentration was derived from the stool samples collected. The analysis population consisted of the PKAS.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Within 24 hours of a dose taken between day 5 and day 10
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Acceptance of formulation was evaluated in all participants who received fidaxomicin oral suspension and vancomycin oral liquid (i.e., participants from birth to =< 6 years and participants > 6 years unable to swallow tablets) by means of a five-point rating scale (awful, poor, fair, good, excellent) by unblinded staff if hospitalized, and by the participant/parents/legal guardian when at home. The analysis population consisted of the FAS.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Days 1 and 7
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From the first dose of study drug administration up to 30 days after EOT (up to day 40)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The total number of deaths (all causes) includes deaths reported after time frame above.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
Fidaxomicin
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vancomycin
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Nov 2014 |
The changes include:
● Throughout the protocol, the age ranges '< 6 months of age' were changed to 'from birth'.
Nonsubstantial changes were made to the protocol:
● To update the contract research organization (CRO) contact for reporting SAEs and contact details of clinical research contact;
● To add text on the coadministration of P-glycoprotein inhibitor to the introduction;
● To add the term palatability to study objectives;
● To update the number of study sites to approximately 65 to 80 sites;
● To move palatability from exploratory endpoint to secondary endpoint, and replace cultures with samples in the exploratory microbiology endpoint;
● To update statistical methodology (several sections);
● To update the schedule of assessments, changing 'Follow-up visit' to 'Follow-up TC';
● To update the timeframe for positive detection of CDAD, changing it from within 48 hours to within 72 hours prior to randomization;
● To update the risk-benefit assessment, adding text on children < 6 months of age and on hypersensitivity reactions;
● To add weight-based dosing instruction of the fidaxomicin oral suspension and the vancomycin oral liquid;
● To update the specified AEs of interest and add lack of efficacy to the special situation events; and
● To include edits for consistency and other minor administrative-type corrections. |
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21 Jul 2015 |
The changes include:
● Inclusion criterion No. 2 was amended to specify that in the US, subjects could only be included if aged ≥ 6 months to < 18 years.
Nonsubstantial changes were made to the protocol:
● To update safety reporting, removing reporting to delegated CRO only for North American sites;
● To update contact details for the clinical research contact;
● To extend the planned study period based on expected recruitment rate;
● To update/revise study design to investigate subjects from birth instead of ≥ 6 months, with the exception of the US;
● To update/revise study design to administer fidaxomicin tablets to subjects aged ≥ 6 years instead of from birth;
● To update concomitant treatment, including the most recent use of fidaxomicin or any macrolide antibiotic to be recorded in the electronic Case Report Form (eCRF);
● To update discontinuation of individual subjects, updating the terminology in alignment with new process for protocol deviation;
● To include instructional text related to reporting certain events as AEs based on local requirements; and
● To include edits for consistency and other minor administrative-type corrections. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |