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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02218372
Other study ID # 2819-CL-0202
Secondary ID 2013-000508-40SU
Status Completed
Phase Phase 3
First received
Last updated
Start date January 9, 2015
Est. completion date March 7, 2018

Study information

Verified date March 2020
Source Astellas Pharma Inc
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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). 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.


Recruitment information / eligibility

Status Completed
Enrollment 148
Est. completion date March 7, 2018
Est. primary completion date March 7, 2018
Accepts healthy volunteers No
Gender All
Age group N/A to 17 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Fidaxomicin oral suspension
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 tablets
Participants aged = 6 years to < 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
Vancomycin oral liquid
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 capsules
Participants aged = 6 years to < 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days.

Locations

Country Name City State
Belgium Site BE32001 Brussels Flemish Brabant
Belgium Site BE32003 Gent
Belgium Site BE32002 Liege
Canada Site CA15003 Oshawa Ontario
France Site FR33002 La Tronche
France Site FR33001 Nice
France Site FR33007 Nice
France Site FR33005 Paris
France Site FR33008 Strasbourg cedex
Germany Site DE49010 Essen
Germany Site DE49002 Frankfurt am M.
Germany Site DE49006 Freiburg
Germany Site DE49004 Mainz
Germany Site DE49001 Muenster
Germany Site DE49003 Saint Augustin
Hungary Site HU36006 Budapest
Hungary Site HU36004 Szeged
Italy Site IT39004 Milano
Italy Site IT39001 Roma
Poland Site PL48012 Bialystok
Poland Site PL48007 Bydgoszcz
Poland Site PL48004 Debica
Poland Site PL48014 Rzeszow
Poland Site PL48006 Tarnow
Poland Site PL48002 Warszawa Mazowieckie
Romania Site RO40005 Bucharest
Spain Site ES34002 Barcelona
Spain Site ES34004 Madrid
Spain Site ES34007 Madrid
Spain Site ES34003 Valencia
United States Site US10028 Chapel Hill North Carolina
United States Site US10010 Chicago Illinois
United States Site US10027 Cincinnati Ohio
United States Site US10038 Fort Worth Texas
United States Site US10004 Indianapolis Indiana
United States Site US10034 Johnson City Tennessee
United States Site US10032 Kansas City Missouri
United States Site US10025 Louisville Kentucky
United States Site US10022 Memphis Tennessee
United States Site US10030 Omaha Nebraska
United States Site US10015 Orange California
United States Site US10037 Salt Lake City Utah
United States Site US10008 Stony Brook New York
United States Site US10014 Toledo Ohio

Sponsors (2)

Lead Sponsor Collaborator
Astellas Pharma Europe B.V. Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Hungary,  Italy,  Poland,  Romania,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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). Up to day 12
Secondary 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. Up to day 19
Secondary 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. Up to day 19
Secondary 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. Up to day 19
Secondary 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. Up to day 26
Secondary 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. Up to day 26
Secondary 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. Up to day 26
Secondary 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. Up to day 33
Secondary 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. Up to day 33
Secondary 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. Up to day 33
Secondary 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. Up to day 40
Secondary 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. Up to day 40
Secondary 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. Up to day 40
Secondary 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. Up to day 10
Secondary 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. Up to day 40
Secondary 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. From the first dose of study drug administration up to 30 days after EOT (up to day 40)
Secondary Plasma Concentrations of Fidaxomicin Drug concentration was derived from the blood samples collected. Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Secondary Plasma Concentrations of Metabolite OP-1118 Drug concentration was derived from the blood samples collected. Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Secondary Metabolite-to-Parent Ratio (MPRconc) Drug concentration was derived from the blood samples collected. Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10
Secondary Fecal Concentrations of Fidaxomicin Drug concentration was derived from the stool samples collected. Within 24 hours of a dose taken between day 5 and day 10
Secondary Fecal Concentrations of Metabolite OP-1118 Drug concentration was derived from the stool samples collected. Within 24 hours of a dose taken between day 5 and day 10
Secondary MPRconc Within 24 Hours of a Dose Drug concentration was derived from the stool samples collected. Within 24 hours of a dose taken between day 5 and day 10
Secondary 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. Days 1 and 7
See also
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Completed NCT01691248 - Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001) Phase 3