Clostridium Difficile-associated Diarrhea (CDAD)Phase 3SUNSHINENCT02218372
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)
A Phase 3 study testing Fidaxomicin oral suspension, Fidaxomicin tablets and Vancomycin oral liquid in people with Clostridium Difficile-associated Diarrhea (CDAD), run by Astellas Pharma Europe B.V. at 44 sites in 10 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Clostridium Difficile-associated Diarrhea (CDAD)
- What is being tested?
- Fidaxomicin oral suspension, Fidaxomicin tablets and Vancomycin oral liquid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 44 sitesin 10 countries
- Study dates
- 9 Jan 2015to 7 Mar 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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:
Show all 12Show fewer
- 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).
Who cannot join
- 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.
Trial locations and contacts
44 sites in 10 countries.
44 sites in 10 countries
United States14 sites
Site US10028
Chapel Hill, North Carolina, 27599
Site US10010
Chicago, Illinois, 60637
Site US10027
Cincinnati, Ohio, 45229-3039
Site US10038
Fort Worth, Texas, 76104
Site US10004
Indianapolis, Indiana, 46202
Site US10034
Johnson City, Tennessee, 37604
Site US10032
Kansas City, Missouri, 64108
Site US10025
Louisville, Kentucky, 40202
Site US10022
Memphis, Tennessee, 38105-2794
Site US10030
Omaha, Nebraska, 68114
Site US10015
Orange, California, 92868
Site US10037
Salt Lake City, Utah, 84113
Site US10008
Stony Brook, New York, 11794-8111
Site US10014
Toledo, Ohio, 43606
Germany6 sites
Site DE49010
Essen, 45122
Site DE49002
Frankfurt Am M., 60596
Site DE49006
Freiburg im Breisgau, 79106
Site DE49004
Mainz, 55131
Site DE49001
Münster, 48149
Site DE49003
Saint Augustin, 53757
Poland6 sites
Site PL48012
Bialystok, 15 -274
Site PL48007
Bydgoszcz, 85-030
Site PL48004
Dębica, 39-200
Site PL48014
Rzeszów, 35-210
Site PL48006
Tarnów, 33-100
Site PL48002
Warsaw, Masovian Voivodeship, 04-730
France5 sites
Site FR33002
La Tronche, 38700
Site FR33001
Nice, 06200
Site FR33007
Nice, 06200
Site FR33005
Paris, 75012
Site FR33008
Strasbourg, 67098
Spain4 sites
Site ES34002
Barcelona, 8950
Site ES34007
Madrid, 28009
Site ES34004
Madrid, 28046
Site ES34003
Valencia, 46026
Belgium3 sites
Site BE32001
Brussels, Flemish Brabant, 1200
Site BE32003
Ghent, 9000
Site BE32002
Liège, 4020
About this study
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
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.
- Being tested
- Fidaxomicin oral suspension, Fidaxomicin tablets, Vancomycin oral liquid, Vancomycin capsules
- Keywords
- Clostridium difficile-associated Diarrhea (CDAD), vancomycin, Clostridium difficile infection, fidaxomicin
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fidaxomicin oral suspensionDrug
Also called Dificid, Dificlir
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.
Fidaxomicin tabletsDrug
Also called Dificlir, Dificid
Participants aged ≥ 6 years to < 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
Vancomycin oral liquidDrug
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.
Vancomycin capsulesDrug
Participants aged ≥ 6 years to < 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days.
| Study group | Role | What they receive |
|---|---|---|
| Fidaxomicin | Experimental | 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. Receives: Drug: Fidaxomicin oral suspension; Drug: Fidaxomicin tablets |
| Vancomycin | Active comparator | 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. Receives: Drug: Vancomycin oral liquid; Drug: Vancomycin capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to day 12
Secondary outcomes (22)
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.
Measured: Up to day 19
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.
Measured: Up to day 19
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.
Measured: Up to day 19
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.
Measured: Up to day 26
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.
Measured: Up to day 26
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.
Measured: Up to day 26
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.
Measured: Up to day 33
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.
Measured: Up to day 33
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.
Measured: Up to day 33
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.
Measured: Up to day 40
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.
Measured: Up to day 40
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.
Measured: Up to day 40
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.
Measured: Up to day 10
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.
Measured: Up to day 40
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.
Measured: From the first dose of study drug administration up to 30 days after EOT (up to day 40)
Plasma Concentrations of Fidaxomicin
Drug concentration was derived from the blood samples collected.
Measured: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Plasma Concentrations of Metabolite OP-1118
Drug concentration was derived from the blood samples collected.
Measured: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Metabolite-to-Parent Ratio (MPRconc)
Drug concentration was derived from the blood samples collected.
Measured: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Fecal Concentrations of Fidaxomicin
Drug concentration was derived from the stool samples collected.
Measured: Within 24 hours of a dose taken between day 5 and day 10
Fecal Concentrations of Metabolite OP-1118
Drug concentration was derived from the stool samples collected.
Measured: Within 24 hours of a dose taken between day 5 and day 10
MPRconc Within 24 Hours of a Dose
Drug concentration was derived from the stool samples collected.
Measured: Within 24 hours of a dose taken between day 5 and day 10
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7
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.
Measured: Days 1 and 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2014 (estimated)
- Study start9 Jan 2015
- Primary completion7 Mar 2018
- Study completion7 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Clostridium Difficile-associated Diarrhea (CDAD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Europe B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Clinical Research Physician, Study director, Astellas Pharma Europe B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02218372
- Sponsor's protocol ID
- 2819-CL-0202
- Other IDs
- 2013-000508-40, SUNSHINE
- Acronym
- SUNSHINE
- Status last verified
- Nov 2024
- First submitted
- 11 Aug 2014
- Last updated
- 26 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Publications
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.
PubMed 31773143Borali 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.
PubMed 27182626
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02218372
- Acronym / sponsor ID
- SUNSHINE / 2819-CL-0202
- Keywords
- Clostridium difficile-associated Diarrhea (CDAD), vancomycin, Clostridium difficile infection, fidaxomicin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 9 Jan 2015 (actual)
- Primary completion
- 7 Mar 2018 (actual)
- Study completion
- 7 Mar 2018 (actual)
- First posted
- 18 Aug 2014 (estimated)
- Results
- Posted 7 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fidaxomicin | Experimental | Drug: Fidaxomicin oral suspension, Drug: Fidaxomicin tabletsParticipants 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. |
| Vancomycin | Active comparator | Drug: Vancomycin oral liquid, Drug: Vancomycin capsulesParticipants 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. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- 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:
- For subjects < 5 years: Negative rotavirus test.
- Female subject of childbearing potential:
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fidaxomicin oral suspensionAlso: Dificid, DificlirParticipants 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. | Drug | Fidaxomicin |
| Fidaxomicin tabletsAlso: Dificlir, DificidParticipants aged ≥ 6 years to < 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days. | Drug | Fidaxomicin |
| Vancomycin oral liquidParticipants 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. | Drug | Vancomycin |
| Vancomycin capsulesParticipants aged ≥ 6 years to < 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days. | Drug | Vancomycin |
Primary outcome
Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days
Time frame: Up to day 12
Initial clinical response (ICR) for ages from birth to < 2 years was defined as absence of watery diarrhea for 2 consecutive treatment days, remaining well until study drug discontinuation. ICR for ages ≥ 2 years to < 18 years was defined as improvement in number and character of bowel movements as determined by < 3 unformed bowel movements (UBMs) per day for 2 consecutive treatment days, remaining well until study drug discontinuation. CCR was defined for both age groups as not requiring further CDAD therapy within 2 days after study drug completion, and was reported with a positive (Yes) or negative (No) outcome. Resolution of diarrhea was assessed during interviews of participant/parent/legal guardian, supplemented by review of personal records (if hospitalized) and checked for presence of watery diarrhea (ages from birth to < 2 years) or number of UBMs (for ages ≥ 2 years to < 18 years).
22 secondary outcomes
Percentage of Participants With Sustained Clinical Response (SCR) at EOT +9 Days
Time frame: Up to day 19
Percentage of Participants With Global Cure (GC) at EOT +9 Days
Time frame: Up to day 19
Percentage of Participants With Recurrence of CDAD at EOT +9 Days
Time frame: Up to day 19
Percentage of Participants With SCR at EOT +16 Days
Time frame: Up to day 26
Percentage of Participants With GC at EOT +16 Days
Time frame: Up to day 26
Percentage of Participants With Recurrence of CDAD at EOT +16 Days
Time frame: Up to day 26
Percentage of Participants With SCR at EOT +23 Days
Time frame: Up to day 33
Percentage of Participants With GC at EOT +23 Days
Time frame: Up to day 33
Percentage of Participants With Recurrence of CDAD at EOT +23 Days
Time frame: Up to day 33
Percentage of Participants With SCR at End of Study (EOS) (EOT +30 Days)
Time frame: Up to day 40
Percentage of Participants With GC at EOS (EOT +30 Days)
Time frame: Up to day 40
Percentage of Participants With Recurrence of CDAD at EOS (EOT +30 Days)
Time frame: Up to day 40
Time to Resolution of Diarrhea (TTROD)
Time frame: Up to day 10
Time to Recurrence of CDAD for Participants With CCR at EOT +2 Days
Time frame: Up to day 40
Number of Participants With Adverse Events (AEs)
Time frame: From the first dose of study drug administration up to 30 days after EOT (up to day 40)
Plasma Concentrations of Fidaxomicin
Time frame: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Plasma Concentrations of Metabolite OP-1118
Time frame: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Metabolite-to-Parent Ratio (MPRconc)
Time frame: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Fecal Concentrations of Fidaxomicin
Time frame: Within 24 hours of a dose taken between day 5 and day 10
Fecal Concentrations of Metabolite OP-1118
Time frame: Within 24 hours of a dose taken between day 5 and day 10
MPRconc Within 24 Hours of a Dose
Time frame: Within 24 hours of a dose taken between day 5 and day 10
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7
Time frame: Days 1 and 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31773143Wolf 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.
- Derived from this study: PubMed 27182626Borali 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.
- Individual participant dataSharing planned: Yes. 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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Research Physician study director
Astellas Pharma Europe B.V.
44 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fidaxomicin oral suspension, Fidaxomicin tablets and Vancomycin oral liquid in people with Clostridium Difficile-associated Diarrhea (CDAD), run by Astellas Pharma Europe B.V. at 44 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Germany, Poland, France, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days (time frame: Up to day 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02218372, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.