Back to resultsA Study to Investigate the Safety and Efficacy of Fidaxomicin (Oral Suspension or Tablets) and Vancomycin (Oral Liquid or Capsules) in Pediatric Subjects With Clostridium Difficile-associated Diarrhea (CDAD) (SUNSHINE)
Primary Purpose
Clostridium Difficile-associated Diarrhea (CDAD)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Fidaxomicin oral suspension
Fidaxomicin tablets
Vancomycin oral liquid
Vancomycin capsules
Sponsored by
About this trial
This is an interventional treatment trial for Clostridium Difficile-associated Diarrhea (CDAD) focused on measuring Clostridium difficile-associated Diarrhea (CDAD), vancomycin, Clostridium difficile infection, fidaxomicin
Eligibility Criteria
Inclusion Criteria:
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).
Exclusion Criteria:
- 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.
Sites / Locations
- Site US10015
- Site US10010
- Site US10004
- Site US10025
- Site US10032
- Site US10030
- Site US10008
- Site US10028
- Site US10027
- Site US10014
- Site US10034
- Site US10022
- Site US10038
- Site US10037
- Site BE32001
- Site BE32003
- Site BE32002
- Site CA15003
- Site FR33002
- Site FR33001
- Site FR33007
- Site FR33005
- Site FR33008
- Site DE49010
- Site DE49002
- Site DE49006
- Site DE49004
- Site DE49001
- Site DE49003
- Site HU36006
- Site HU36004
- Site IT39004
- Site IT39001
- Site PL48002
- Site PL48012
- Site PL48007
- Site PL48004
- Site PL48014
- Site PL48006
- Site RO40005
- Site ES34002
- Site ES34007
- Site ES34004
- Site ES34003
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Fidaxomicin
Vancomycin
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.
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days
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).
Secondary Outcome Measures
Percentage of Participants With Sustained Clinical Response (SCR) at EOT +9 Days
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.
Percentage of Participants With Global Cure (GC) at EOT +9 Days
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.
Percentage of Participants With Recurrence of CDAD at EOT +9 Days
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.
Percentage of Participants With SCR at EOT +16 Days
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.
Percentage of Participants With GC at EOT +16 Days
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.
Percentage of Participants With Recurrence of CDAD at EOT +16 Days
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.
Percentage of Participants With SCR at EOT +23 Days
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.
Percentage of Participants With GC at EOT +23 Days
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.
Percentage of Participants With Recurrence of CDAD at EOT +23 Days
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.
Percentage of Participants With SCR at End of Study (EOS) (EOT +30 Days)
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.
Percentage of Participants With GC at EOS (EOT +30 Days)
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.
Percentage of Participants With Recurrence of CDAD at EOS (EOT +30 Days)
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.
Time to Resolution of Diarrhea (TTROD)
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.
Time to Recurrence of CDAD for Participants With CCR at EOT +2 Days
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 estimable denoted as NA. 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.
Number of Participants With Adverse Events (AEs)
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.
Plasma Concentrations of Fidaxomicin
Drug concentration was derived from the blood samples collected.
Plasma Concentrations of Metabolite OP-1118
Drug concentration was derived from the blood samples collected.
Metabolite-to-Parent Ratio (MPRconc)
Drug concentration was derived from the blood samples collected.
Fecal Concentrations of Fidaxomicin
Drug concentration was derived from the stool samples collected.
Fecal Concentrations of Metabolite OP-1118
Drug concentration was derived from the stool samples collected.
MPRconc Within 24 Hours of a Dose
Drug concentration was derived from the stool samples collected.
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7
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.
Full Information
NCT ID
NCT02218372
First Posted
August 11, 2014
Last Updated
March 10, 2020
Sponsor
Astellas Pharma Europe B.V.
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02218372
Brief Title
A Study to Investigate the Safety and Efficacy of Fidaxomicin (Oral Suspension or Tablets) and Vancomycin (Oral Liquid or Capsules) in Pediatric Subjects With Clostridium Difficile-associated Diarrhea (CDAD)
Acronym
SUNSHINE
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
January 9, 2015 (Actual)
Primary Completion Date
March 7, 2018 (Actual)
Study Completion Date
March 7, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Europe B.V.
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile-associated Diarrhea (CDAD)
Keywords
Clostridium difficile-associated Diarrhea (CDAD), vancomycin, Clostridium difficile infection, fidaxomicin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
148 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fidaxomicin
Arm Type
Experimental
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 Title
Vancomycin
Arm Type
Active Comparator
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.
Intervention Type
Drug
Intervention Name(s)
Fidaxomicin oral suspension
Other Intervention Name(s)
Dificid, Dificlir
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Fidaxomicin tablets
Other Intervention Name(s)
Dificlir, Dificid
Intervention Description
Participants aged ≥ 6 years to < 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
Intervention Type
Drug
Intervention Name(s)
Vancomycin oral liquid
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Vancomycin capsules
Intervention Description
Participants aged ≥ 6 years to < 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days.
Primary Outcome Measure Information:
Title
Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days
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).
Time Frame
Up to day 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Clinical Response (SCR) at EOT +9 Days
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.
Time Frame
Up to day 19
Title
Percentage of Participants With Global Cure (GC) at EOT +9 Days
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.
Time Frame
Up to day 19
Title
Percentage of Participants With Recurrence of CDAD at EOT +9 Days
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.
Time Frame
Up to day 19
Title
Percentage of Participants With SCR at EOT +16 Days
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.
Time Frame
Up to day 26
Title
Percentage of Participants With GC at EOT +16 Days
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.
Time Frame
Up to day 26
Title
Percentage of Participants With Recurrence of CDAD at EOT +16 Days
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.
Time Frame
Up to day 26
Title
Percentage of Participants With SCR at EOT +23 Days
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.
Time Frame
Up to day 33
Title
Percentage of Participants With GC at EOT +23 Days
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.
Time Frame
Up to day 33
Title
Percentage of Participants With Recurrence of CDAD at EOT +23 Days
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.
Time Frame
Up to day 33
Title
Percentage of Participants With SCR at End of Study (EOS) (EOT +30 Days)
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.
Time Frame
Up to day 40
Title
Percentage of Participants With GC at EOS (EOT +30 Days)
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.
Time Frame
Up to day 40
Title
Percentage of Participants With Recurrence of CDAD at EOS (EOT +30 Days)
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.
Time Frame
Up to day 40
Title
Time to Resolution of Diarrhea (TTROD)
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.
Time Frame
Up to day 10
Title
Time to Recurrence of CDAD for Participants With CCR at EOT +2 Days
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 estimable denoted as NA. 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.
Time Frame
Up to day 40
Title
Number of Participants With Adverse Events (AEs)
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.
Time Frame
From the first dose of study drug administration up to 30 days after EOT (up to day 40)
Title
Plasma Concentrations of Fidaxomicin
Description
Drug concentration was derived from the blood samples collected.
Time Frame
Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Title
Plasma Concentrations of Metabolite OP-1118
Description
Drug concentration was derived from the blood samples collected.
Time Frame
Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Title
Metabolite-to-Parent Ratio (MPRconc)
Description
Drug concentration was derived from the blood samples collected.
Time Frame
Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Title
Fecal Concentrations of Fidaxomicin
Description
Drug concentration was derived from the stool samples collected.
Time Frame
Within 24 hours of a dose taken between day 5 and day 10
Title
Fecal Concentrations of Metabolite OP-1118
Description
Drug concentration was derived from the stool samples collected.
Time Frame
Within 24 hours of a dose taken between day 5 and day 10
Title
MPRconc Within 24 Hours of a Dose
Description
Drug concentration was derived from the stool samples collected.
Time Frame
Within 24 hours of a dose taken between day 5 and day 10
Title
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7
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.
Time Frame
Days 1 and 7
10. Eligibility
Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Research Physician
Organizational Affiliation
Astellas Pharma Europe B.V.
Official's Role
Study Director
Facility Information:
Facility Name
Site US10015
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Site US10010
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Site US10004
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Site US10025
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Site US10032
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Site US10030
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Site US10008
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794-8111
Country
United States
Facility Name
Site US10028
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Site US10027
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Site US10014
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
Site US10034
City
Johnson City
State/Province
Tennessee
ZIP/Postal Code
37604
Country
United States
Facility Name
Site US10022
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105-2794
Country
United States
Facility Name
Site US10038
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Site US10037
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Site BE32001
City
Brussels
State/Province
Flemish Brabant
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Site BE32003
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Site BE32002
City
Liege
ZIP/Postal Code
4020
Country
Belgium
Facility Name
Site CA15003
City
Oshawa
State/Province
Ontario
ZIP/Postal Code
L1G 2B9
Country
Canada
Facility Name
Site FR33002
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
Site FR33001
City
Nice
ZIP/Postal Code
06200
Country
France
Facility Name
Site FR33007
City
Nice
ZIP/Postal Code
06200
Country
France
Facility Name
Site FR33005
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Site FR33008
City
Strasbourg cedex
ZIP/Postal Code
67098
Country
France
Facility Name
Site DE49010
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Site DE49002
City
Frankfurt am M.
ZIP/Postal Code
60596
Country
Germany
Facility Name
Site DE49006
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Site DE49004
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Site DE49001
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Site DE49003
City
Saint Augustin
ZIP/Postal Code
53757
Country
Germany
Facility Name
Site HU36006
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
Site HU36004
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
Facility Name
Site IT39004
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Site IT39001
City
Roma
ZIP/Postal Code
165
Country
Italy
Facility Name
Site PL48002
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
04-730
Country
Poland
Facility Name
Site PL48012
City
Bialystok
ZIP/Postal Code
15 -274
Country
Poland
Facility Name
Site PL48007
City
Bydgoszcz
ZIP/Postal Code
85-030
Country
Poland
Facility Name
Site PL48004
City
Debica
ZIP/Postal Code
39-200
Country
Poland
Facility Name
Site PL48014
City
Rzeszow
ZIP/Postal Code
35-210
Country
Poland
Facility Name
Site PL48006
City
Tarnow
ZIP/Postal Code
33-100
Country
Poland
Facility Name
Site RO40005
City
Bucharest
Country
Romania
Facility Name
Site ES34002
City
Barcelona
ZIP/Postal Code
8950
Country
Spain
Facility Name
Site ES34007
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Site ES34004
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Site ES34003
City
Valencia
ZIP/Postal Code
46026
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
IPD Sharing Time Frame
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
IPD Sharing Access Criteria
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Citations:
PubMed Identifier
31773143
Citation
Wolf J, Kalocsai K, Fortuny C, Lazar S, Bosis S, Korczowski B, Petit A, Bradford D, Croos-Dabrera R, Incera E, Melis J, van Maanen R. Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE). Clin Infect Dis. 2020 Dec 17;71(10):2581-2588. doi: 10.1093/cid/ciz1149.
Results Reference
derived
PubMed Identifier
27182626
Citation
Borali E, De Giacomo C. Clostridium Difficile Infection in Children: A Review. J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):e130-e140. doi: 10.1097/MPG.0000000000001264.
Results Reference
derived
Links:
URL
https://astellasclinicalstudyresults.com/study.aspx?ID=362
Description
Link to results on Astellas Clinical Study Results website
Learn more about this trial
A Study to Investigate the Safety and Efficacy of Fidaxomicin (Oral Suspension or Tablets) and Vancomycin (Oral Liquid or Capsules) in Pediatric Subjects With Clostridium Difficile-associated Diarrhea (CDAD)
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