Clinical trial NCT02218372: 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)
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Difficile-associated Diarrhea (CDAD)
Keywords: Clostridium difficile-associated Diarrhea (CDAD)
vancomycin
Clostridium difficile infection
fidaxomicin
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2014-08-18
Enrollment: 148
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days
timeFrame: Up to day 12
Secondary outcomes:
measure: Percentage of Participants With Sustained Clinical Response (SCR) at EOT +9 Days
timeFrame: Up to day 19
measure: Percentage of Participants With Global Cure (GC) at EOT +9 Days
timeFrame: Up to day 19
measure: Percentage of Participants With Recurrence of CDAD at EOT +9 Days
timeFrame: Up to day 19
measure: Percentage of Participants With SCR at EOT +16 Days
timeFrame: Up to day 26
measure: Percentage of Participants With GC at EOT +16 Days
timeFrame: Up to day 26
measure: Percentage of Participants With Recurrence of CDAD at EOT +16 Days
timeFrame: Up to day 26
measure: Percentage of Participants With SCR at EOT +23 Days
timeFrame: Up to day 33
measure: Percentage of Participants With GC at EOT +23 Days
timeFrame: Up to day 33
measure: Percentage of Participants With Recurrence of CDAD at EOT +23 Days
timeFrame: Up to day 33
measure: Percentage of Participants With SCR at End of Study (EOS) (EOT +30 Days)
timeFrame: Up to day 40
measure: Percentage of Participants With GC at EOS (EOT +30 Days)
timeFrame: Up to day 40
measure: Percentage of Participants With Recurrence of CDAD at EOS (EOT +30 Days)
timeFrame: Up to day 40
measure: Time to Resolution of Diarrhea (TTROD)
timeFrame: Up to day 10
measure: Time to Recurrence of CDAD for Participants With CCR at EOT +2 Days
timeFrame: Up to day 40
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From the first dose of study drug administration up to 30 days after EOT (up to day 40)
measure: Plasma Concentrations of Fidaxomicin
timeFrame: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
measure: Plasma Concentrations of Metabolite OP-1118
timeFrame: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
measure: Metabolite-to-Parent Ratio (MPRconc)
timeFrame: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
measure: Fecal Concentrations of Fidaxomicin
timeFrame: Within 24 hours of a dose taken between day 5 and day 10
measure: Fecal Concentrations of Metabolite OP-1118
timeFrame: Within 24 hours of a dose taken between day 5 and day 10
measure: MPRconc Within 24 Hours of a Dose
timeFrame: Within 24 hours of a dose taken between day 5 and day 10
measure: Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7
timeFrame: Days 1 and 7
Other outcomes:
Locations:
city: Orange
country: United States
facility: Site US10015
state: California
city: Chicago
country: United States
facility: Site US10010
state: Illinois
city: Indianapolis
country: United States
facility: Site US10004
state: Indiana
city: Louisville
country: United States
facility: Site US10025
state: Kentucky
city: Kansas City
country: United States
facility: Site US10032
state: Missouri
city: Omaha
country: United States
facility: Site US10030
state: Nebraska
city: Stony Brook
country: United States
facility: Site US10008
state: New York
city: Chapel Hill
country: United States
facility: Site US10028
state: North Carolina
city: Cincinnati
country: United States
facility: Site US10027
state: Ohio
city: Toledo
country: United States
facility: Site US10014
state: Ohio
city: Johnson City
country: United States
facility: Site US10034
state: Tennessee
city: Memphis
country: United States
facility: Site US10022
state: Tennessee
city: Fort Worth
country: United States
facility: Site US10038
state: Texas
city: Salt Lake City
country: United States
facility: Site US10037
state: Utah
city: Brussels
country: Belgium
facility: Site BE32001
state: Flemish Brabant
city: Gent
country: Belgium
facility: Site BE32003
city: Liege
country: Belgium
facility: Site BE32002
city: Oshawa
country: Canada
facility: Site CA15003
state: Ontario
city: La Tronche
country: France
facility: Site FR33002
city: Nice
country: France
facility: Site FR33001
city: Nice
country: France
facility: Site FR33007
city: Paris
country: France
facility: Site FR33005
city: Strasbourg cedex
country: France
facility: Site FR33008
city: Essen
country: Germany
facility: Site DE49010
city: Frankfurt am M.
country: Germany
facility: Site DE49002
city: Freiburg
country: Germany
facility: Site DE49006
city: Mainz
country: Germany
facility: Site DE49004
city: Muenster
country: Germany
facility: Site DE49001
city: Saint Augustin
country: Germany
facility: Site DE49003
city: Budapest
country: Hungary
facility: Site HU36006
city: Szeged
country: Hungary
facility: Site HU36004
city: Milano
country: Italy
facility: Site IT39004
city: Roma
country: Italy
facility: Site IT39001
city: Warszawa
country: Poland
facility: Site PL48002
state: Mazowieckie
city: Bialystok
country: Poland
facility: Site PL48012
city: Bydgoszcz
country: Poland
facility: Site PL48007
city: Debica
country: Poland
facility: Site PL48004
city: Rzeszow
country: Poland
facility: Site PL48014
city: Tarnow
country: Poland
facility: Site PL48006
city: Bucharest
country: Romania
facility: Site RO40005
city: Barcelona
country: Spain
facility: Site ES34002
city: Madrid
country: Spain
facility: Site ES34007
city: Madrid
country: Spain
facility: Site ES34004
city: Valencia
country: Spain
facility: Site ES34003
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Research Physician
role: STUDY_DIRECTOR
References:
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.
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.