A Phase 3 interventional study of Fidaxomicin oral suspension and Fidaxomicin tablets in Clostridium Difficile-associated Diarrhea (CDAD), sponsored by Astellas Pharma Europe B.V.. Completed at 44 sites in 10 countries. Open to participants aged Up to 17 Years. Per ClinicalTrials.gov, last updated 2024-11-26.
Sponsored by Astellas Pharma Europe B.V. (part of Astellas Pharma Inc) · Phase 3, Interventional, and Treatment
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.
251 studies on the registry are indexed under Clostridium Infections; 51 are open to participants now.
This study's enrollment of 148 is above the median of 64 across 185 interventional studies indexed under Clostridium Infections.
Browse Clostridium Infections studies →Astellas Pharma Europe B.V. is the lead sponsor of 94 studies on the registry; none are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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:
Female subject of :
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Fidaxomicin oral suspension · Drug: Fidaxomicin tablets
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.
Drug: Vancomycin oral liquid · Drug: Vancomycin capsules
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.
Also known as: Dificid, Dificlir
Participants aged ≥ 6 years to \< 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
Also known as: Dificlir, Dificid
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.
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).
Time frame: Up to day 12
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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
Metabolite-to-Parent Ratio (MPRconc)
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
Fecal Concentrations of Fidaxomicin
Drug concentration was derived from the stool samples collected.
Time frame: 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.
Time frame: 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.
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
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
Pediatric participants with clostridium difficile-associated diarrhea (CDAD) were enrolled in this multicenter study.
| Milestone | Fidaxomicin | Vancomycin |
|---|---|---|
| Started | 100 | 48 |
| Treated | 98 | 44 |
| Completed | 95 | 42 |
| Not completed | 5 | 6 |
| Withdrew: Adverse event | 1 | 1 |
| Withdrew: Miscellaneous | 2 | 1 |
| Withdrew: Randomized but did not receive treatment | 2 | 3 |
| Withdrew: Withdrawal by parent/guardian | 0 | 1 |
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).
| percentage of participants | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days | 77.6 (68.0 to 85.4) | 70.5 (54.8 to 83.2) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With Sustained Clinical Response (SCR) at EOT +9 Days | 94.7 (87.1 to 98.5) | 77.4 (58.9 to 90.4) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With Global Cure (GC) at EOT +9 Days | 75.5 (65.8 to 83.6) | 54.5 (38.8 to 69.6) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With Recurrence of CDAD at EOT +9 Days | 5.3 (1.5 to 12.9) | 22.6 (9.6 to 41.1) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With SCR at EOT +16 Days | 89.5 (80.3 to 95.3) | 71.0 (52.0 to 85.8) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With GC at EOT +16 Days | 71.4 (61.4 to 80.1) | 52.3 (36.7 to 67.5) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With Recurrence of CDAD at EOT +16 Days | 7.9 (3.0 to 16.4) | 25.8 (11.9 to 44.6) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With SCR at EOT +23 Days | 85.5 (75.6 to 92.5) | 71.0 (52.0 to 85.8) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With GC at EOT +23 Days | 68.4 (58.2 to 77.4) | 50.0 (34.6 to 65.4) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With Recurrence of CDAD at EOT +23 Days | 11.8 (5.6 to 21.3) | 29.0 (14.2 to 48.0) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With SCR at End of Study (EOS) (EOT +30 Days) | 85.5 (75.6 to 92.5) | 71.0 (52.0 to 85.8) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With GC at EOS (EOT +30 Days) | 68.4 (58.2 to 77.4) | 50.0 (34.6 to 65.4) |
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 | Fidaxomicin | Vancomycin |
|---|---|---|
| Percentage of Participants With Recurrence of CDAD at EOS (EOT +30 Days) | 11.8 (5.6 to 21.3) | 29.0 (14.2 to 48.0) |
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.
| hours | Fidaxomicin | Vancomycin |
|---|---|---|
| Time to Resolution of Diarrhea (TTROD) | 58 (29.0 to 122.0) | 97 (42.0 to 146.0) |
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.
| days | Fidaxomicin | Vancomycin |
|---|---|---|
| Time to Recurrence of CDAD for Participants With CCR at EOT +2 Days | 25 (NA to NA) | 26 (NA to NA) |
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.
| Participants | Fidaxomicin | Vancomycin |
|---|---|---|
| TEAE | 72 | 33 |
| Drug-related TEAE | 7 | 5 |
| Serious TEAE | 24 | 12 |
| Drug-related Serious TEAE | 0 | 0 |
| Moderate TEAE | 39 | 14 |
| Drug-related Moderate TEAE | 4 | 1 |
| Mild TEAE | 56 | 30 |
| Drug-related Mild TEAE | 3 | 4 |
| TEAE Leading to Death | 3 | 0 |
| Drug-related TEAE Leading to Death | 0 | 0 |
| TEAE leading to Withdrawal of Treatment (Tx) | 1 | 1 |
| Drug-related TEAE Leading to Withdrawal of Tx | 0 | 0 |
Drug concentration was derived from the blood samples collected.
| ng/mL | Fidaxomin All Formulations | Fidaxomicin Oral Suspension | Fidaxomicin Tablets |
|---|---|---|---|
| Predose | 20.17 ± 40.16 | 15.26 ± 20.43 | 30.16 ± 63.27 |
| Postdose | 39.41 ± 62.15 | 34.60 ± 57.79 | 48.53 ± 69.85 |
Drug concentration was derived from the blood samples collected.
| ng/mL | Fidaxomin All Formulations | Fidaxomicin Oral Suspension | Fidaxomicin Tablets |
|---|---|---|---|
| Predose | 63.04 ± 171.97 | 42.18 ± 76.76 | 105.54 ± 277.67 |
| Postdose | 116.64 ± 259.10 | 102.38 ± 245.19 | 143.63 ± 286.31 |
Drug concentration was derived from the blood samples collected.
| ratio | Fidaxomin All Formulations | Fidaxomicin Oral Suspension | Fidaxomicin Tablets |
|---|---|---|---|
| Predose | 3.18 ± 1.42 | 3.24 ± 1.46 | 3.05 ± 1.35 |
| Postdose | 2.86 ± 1.18 | 2.95 ± 1.23 | 2.69 ± 1.06 |
Drug concentration was derived from the stool samples collected.
| μg/g | Fidaxomin All Formulations | Fidaxomicin Oral Suspension | Fidaxomicin Tablets |
|---|---|---|---|
| Fecal Concentrations of Fidaxomicin | 2685.56 ± 2476.92 | 2969.87 ± 2713.58 | 2190.63 ± 1948.68 |
Drug concentration was derived from the stool samples collected.
| μg/g | Fidaxomin All Formulations | Fidaxomicin Oral Suspension | Fidaxomicin Tablets |
|---|---|---|---|
| Fecal Concentrations of Metabolite OP-1118 | 889.23 ± 817.83 | 789.15 ± 728.58 | 1059.73 ± 941.04 |
Drug concentration was derived from the stool samples collected.
| ratio | Fidaxomin All Formulations | Fidaxomicin Oral Suspension | Fidaxomicin Tablets |
|---|---|---|---|
| MPRconc Within 24 Hours of a Dose | 0.43 ± 0.31 | 0.32 ± 0.19 | 0.63 ± 0.38 |
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.
| Participants | Fidaxomicin Oral Suspension | Vancomycin Oral Liquid |
|---|---|---|
| Day 1 Awful | 4 | 5 |
| Day 1 Poor | 6 | 3 |
| Day 1 Fair | 13 | 6 |
| Day 1 Good | 19 | 7 |
| Day 1 Excellent | 13 | 4 |
| Day 1 Missing | 12 | 5 |
| Day 7 Awful | 2 | 3 |
| Day 7 Poor | 5 | 5 |
| Day 7 Fair | 8 | 5 |
| Day 7 Good | 21 | 9 |
| Day 7 Excellent | 16 | 3 |
| Day 7 Missing | 15 | 5 |
Collected over From the first dose of study drug administration up to 30 days after EOT (up to day 40). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fidaxomicin | 3/98 (3.1%) | 24/98 (24.5%) | 36/98 (36.7%) |
| Vancomycin | 2/44 (4.5%) | 12/44 (27.3%) | 21/44 (47.7%) |
| Event | Fidaxomicin | Vancomycin |
|---|---|---|
| PyrexiaGeneral disorders | 2/98 | 2/44 |
| Febrile neutropeniaBlood and lymphatic system disorders | 3/98 | 1/44 |
| ColitisGastrointestinal disorders | 0/98 | 1/44 |
| DiarrhoeaGastrointestinal disorders | 0/98 | 1/44 |
| Gastrointestinal necrosisGastrointestinal disorders | 0/98 | 1/44 |
| Ileus paralyticGastrointestinal disorders | 0/98 | 1/44 |
| Intestinal obstructionGastrointestinal disorders | 0/98 | 1/44 |
| Clostridium difficile colitisInfections and infestations | 0/98 | 1/44 |
| Fungal sepsisInfections and infestations | 0/98 | 1/44 |
| InfluenzaInfections and infestations | 0/98 | 1/44 |
| Event | Fidaxomicin | Vancomycin |
|---|---|---|
| Abdominal painGastrointestinal disorders | 5/98 | 9/44 |
| PyrexiaGeneral disorders | 11/98 | 8/44 |
| VomitingGastrointestinal disorders | 7/98 | 6/44 |
| DiarrhoeaGastrointestinal disorders | 7/98 | 4/44 |
| HeadacheNervous system disorders | 8/98 | 0/44 |
| Oral candidiasisInfections and infestations | 3/98 | 3/44 |
| PruritusSkin and subcutaneous tissue disorders | 3/98 | 3/44 |
| ConstipationGastrointestinal disorders | 5/98 | 1/44 |
The baseline analysis set consisted of the Intent-to-treat (ITT) population. The ITT analysis set consisted of all randomized participants, irrespective of a participant having received a study drug (fidaxomicin or vancomycin) or not.
| Age, Continuous(months) | Fidaxomicin | Vancomycin | Total |
|---|---|---|---|
| Mean | 79.7 ± 61.8 | 77.5 ± 59.2 | 79 ± 60.8 |
| Sex: Female, Male(Participants) | Fidaxomicin | Vancomycin | Total |
|---|---|---|---|
| Female | 41 | 21 | 62 |
| Male | 59 | 27 | 86 |
| Race/Ethnicity, Customized(Participants) | Fidaxomicin | Vancomycin | Total |
|---|---|---|---|
| White | 83 | 36 | 119 |
| Black or African American | 6 | 5 | 11 |
| Asian | 2 | 0 | 2 |
| Other | 4 | 1 | 5 |
| Missing | 5 | 6 | 11 |
| Ethnicity(Participants) | Fidaxomicin | Vancomycin | Total |
|---|---|---|---|
| Hispanic or Latino | 12 | 5 | 17 |
| Not Hispanic or Latino | 82 | 37 | 119 |
| Missing | 6 | 6 | 12 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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/.
Supporting information: Study protocol, Statistical analysis plan, Clinical study report
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.
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.
Data sharing details ↗ · www.clinicaltrials.astellas.com
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Studies of the drug tested here: Fidaxomicin