Trial Outcomes & Findings for 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) (NCT NCT02218372)

Last Updated: 2024-11-26

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

148 participants

Primary outcome timeframe

Up to day 12

Results posted on

2024-11-26

Participant Flow

Pediatric participants with clostridium difficile-associated diarrhea (CDAD) were enrolled in this multicenter study.

Eligible participants who met inclusion criteria and none of the exclusion criteria were enrolled, 159 participants were assessed for eligibility of whom 148 were randomized. Participants were randomized to either fidaxomicin or vancomycin in a 2:1 ratio, stratified by age group.

Participant milestones

Participant milestones
Measure	Fidaxomicin 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.	Vancomycin 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.
Overall Study STARTED	100	48
Overall Study Treated	98	44
Overall Study COMPLETED	95	42
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Fidaxomicin 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.	Vancomycin 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.
Overall Study Adverse Event	1	1
Overall Study Miscellaneous	2	1
Overall Study Randomized but did not receive treatment	2	3
Overall Study Withdrawal by Parent/Guardian	0	1

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fidaxomicin n=100 Participants 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.	Vancomycin n=48 Participants 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.	Total n=148 Participants Total of all reporting groups
Age, Continuous	79.7 months STANDARD_DEVIATION 61.8 • n=5 Participants	77.5 months STANDARD_DEVIATION 59.2 • n=7 Participants	79 months STANDARD_DEVIATION 60.8 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	21 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	27 Participants n=7 Participants	86 Participants n=5 Participants
Race/Ethnicity, Customized White	83 Participants n=5 Participants	36 Participants n=7 Participants	119 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Missing	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity Hispanic or Latino	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity Not Hispanic or Latino	82 Participants n=5 Participants	37 Participants n=7 Participants	119 Participants n=5 Participants
Ethnicity Missing	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to day 12

Population: The analysis population consisted of the full analysis set (FAS) which consisted of all randomized participants who received at least 1 dose of study drug. In the FAS, participants were allocated to the treatment arm corresponding to the study medication that the participant was randomized to (treatment allocation as randomized).

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=44 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days	77.6 percentage of participants Interval 68.0 to 85.4	70.5 percentage of participants Interval 54.8 to 83.2	—

SECONDARY outcome

Timeframe: Up to day 19

Population: The analysis population consisted of the FAS (participants with CCR at EOT +2 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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With Sustained Clinical Response (SCR) at EOT +9 Days	94.7 percentage of participants Interval 87.1 to 98.5	77.4 percentage of participants Interval 58.9 to 90.4	—

SECONDARY outcome

Timeframe: Up to day 19

Population: The analysis population consisted of the FAS.

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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=44 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With Global Cure (GC) at EOT +9 Days	75.5 percentage of participants Interval 65.8 to 83.6	54.5 percentage of participants Interval 38.8 to 69.6	—

SECONDARY outcome

Timeframe: Up to day 19

Population: The analysis population consisted of the FAS (participants with CCR at EOT +2 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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With Recurrence of CDAD at EOT +9 Days	5.3 percentage of participants Interval 1.5 to 12.9	22.6 percentage of participants Interval 9.6 to 41.1	—

SECONDARY outcome

Timeframe: Up to day 26

Population: The analysis population consisted of the FAS (participants with CCR at EOT +2 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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With SCR at EOT +16 Days	89.5 percentage of participants Interval 80.3 to 95.3	71.0 percentage of participants Interval 52.0 to 85.8	—

SECONDARY outcome

Timeframe: Up to day 26

Population: The analysis population consisted of the FAS.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=44 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With GC at EOT +16 Days	71.4 percentage of participants Interval 61.4 to 80.1	52.3 percentage of participants Interval 36.7 to 67.5	—

SECONDARY outcome

Timeframe: Up to day 26

Population: The analysis population consisted of the FAS (participants with CCR at EOT +2 days).

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With Recurrence of CDAD at EOT +16 Days	7.9 percentage of participants Interval 3.0 to 16.4	25.8 percentage of participants Interval 11.9 to 44.6	—

SECONDARY outcome

Timeframe: Up to day 33

Population: The analysis population consisted of the FAS (participants with CCR at EOT +2 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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With SCR at EOT +23 Days	85.5 percentage of participants Interval 75.6 to 92.5	71.0 percentage of participants Interval 52.0 to 85.8	—

SECONDARY outcome

Timeframe: Up to day 33

Population: The analysis population consisted of the FAS.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=44 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With GC at EOT +23 Days	68.4 percentage of participants Interval 58.2 to 77.4	50.0 percentage of participants Interval 34.6 to 65.4	—

SECONDARY outcome

Timeframe: Up to day 33

Population: The analysis population consisted of the FAS (participants with CCR at EOT +2 days).

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With Recurrence of CDAD at EOT +23 Days	11.8 percentage of participants Interval 5.6 to 21.3	29.0 percentage of participants Interval 14.2 to 48.0	—

SECONDARY outcome

Timeframe: Up to day 40

Population: The analysis population consisted of the FAS (participants with CCR at EOT +2 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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With SCR at End of Study (EOS) (EOT +30 Days)	85.5 percentage of participants Interval 75.6 to 92.5	71.0 percentage of participants Interval 52.0 to 85.8	—

SECONDARY outcome

Timeframe: Up to day 40

Population: The analysis population consisted of the FAS.

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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=44 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With GC at EOS (EOT +30 Days)	68.4 percentage of participants Interval 58.2 to 77.4	50.0 percentage of participants Interval 34.6 to 65.4	—

SECONDARY outcome

Timeframe: Up to day 40

Population: The analysis population consisted of the FAS (participants with CCR at EOT +2 days).

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Percentage of Participants With Recurrence of CDAD at EOS (EOT +30 Days)	11.8 percentage of participants Interval 5.6 to 21.3	29.0 percentage of participants Interval 14.2 to 48.0	—

SECONDARY outcome

Timeframe: Up to day 10

Population: The analysis population consisted of the FAS.

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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=44 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Time to Resolution of Diarrhea (TTROD)	58 hours Interval 29.0 to 122.0	97 hours Interval 42.0 to 146.0	—

SECONDARY outcome

Timeframe: Up to day 40

Population: The analysis population consisted of the FAS (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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=76 Participants 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.	Vancomycin n=31 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Time to Recurrence of CDAD for Participants With CCR at EOT +2 Days	25 days Data for Median was estimated and the 95% CI could not be estimated due to low event rate.	26 days Data for Median was estimated and the 95% CI could not be estimated due to low event rate.	—

SECONDARY outcome

Timeframe: From the first dose of study drug administration up to 30 days after EOT (up to day 40)

Population: The analysis population consisted of the safety analysis set (SAF), which consisted of all randomized participants who received at least 1 study drug dose. In the SAF, participants were allocated to the treatment arm corresponding to study drug first administered (fidaxomicin or vancomycin), even if it differed from the treatment randomized to.

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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=44 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Number of Participants With Adverse Events (AEs) Drug-related TEAE Leading to Death	0 Participants	0 Participants	—
Number of Participants With Adverse Events (AEs) TEAE	72 Participants	33 Participants	—
Number of Participants With Adverse Events (AEs) Drug-related TEAE	7 Participants	5 Participants	—
Number of Participants With Adverse Events (AEs) Serious TEAE	24 Participants	12 Participants	—
Number of Participants With Adverse Events (AEs) Drug-related Serious TEAE	0 Participants	0 Participants	—
Number of Participants With Adverse Events (AEs) Moderate TEAE	39 Participants	14 Participants	—
Number of Participants With Adverse Events (AEs) Drug-related Moderate TEAE	4 Participants	1 Participants	—
Number of Participants With Adverse Events (AEs) Mild TEAE	56 Participants	30 Participants	—
Number of Participants With Adverse Events (AEs) Drug-related Mild TEAE	3 Participants	4 Participants	—
Number of Participants With Adverse Events (AEs) TEAE Leading to Death	3 Participants	0 Participants	—
Number of Participants With Adverse Events (AEs) TEAE leading to Withdrawal of Treatment (Tx)	1 Participants	1 Participants	—
Number of Participants With Adverse Events (AEs) Drug-related TEAE Leading to Withdrawal of Tx	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10

Population: The analysis population consisted of the pharmacokinetics analysis set (PKAS). The PKAS consisted of all participants randomized to fidaxomicin, having received at least 1 dose of fidaxomicin and having at least 1 valid measurement of plasma concentration or fecal concentration of fidaxomicin or its main metabolite OP-1118.

Drug concentration was derived from the blood samples collected.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=67 Participants 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.	Fidaxomicin Tablets n=31 Participants Participants received fidaxomicin tablets formulation.
Plasma Concentrations of Fidaxomicin Postdose	39.41 ng/mL Standard Deviation 62.15	34.60 ng/mL Standard Deviation 57.79	48.53 ng/mL Standard Deviation 69.85
Plasma Concentrations of Fidaxomicin Predose	20.17 ng/mL Standard Deviation 40.16	15.26 ng/mL Standard Deviation 20.43	30.16 ng/mL Standard Deviation 63.27

SECONDARY outcome

Timeframe: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10

Population: The analysis population consisted of the PKAS.

Drug concentration was derived from the blood samples collected.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=67 Participants 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.	Fidaxomicin Tablets n=31 Participants Participants received fidaxomicin tablets formulation.
Plasma Concentrations of Metabolite OP-1118 Predose	63.04 ng/mL Standard Deviation 171.97	42.18 ng/mL Standard Deviation 76.76	105.54 ng/mL Standard Deviation 277.67
Plasma Concentrations of Metabolite OP-1118 Postdose	116.64 ng/mL Standard Deviation 259.10	102.38 ng/mL Standard Deviation 245.19	143.63 ng/mL Standard Deviation 286.31

SECONDARY outcome

Timeframe: Within 30 minutes predose and 1 to 5 hours postdose taken between day 5 and day 10

Population: The analysis population consisted of the PKAS.

Drug concentration was derived from the blood samples collected.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=98 Participants 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.	Vancomycin n=67 Participants 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.	Fidaxomicin Tablets n=31 Participants Participants received fidaxomicin tablets formulation.
Metabolite-to-Parent Ratio (MPRconc) Predose	3.18 ratio Standard Deviation 1.42	3.24 ratio Standard Deviation 1.46	3.05 ratio Standard Deviation 1.35
Metabolite-to-Parent Ratio (MPRconc) Postdose	2.86 ratio Standard Deviation 1.18	2.95 ratio Standard Deviation 1.23	2.69 ratio Standard Deviation 1.06

SECONDARY outcome

Timeframe: Within 24 hours of a dose taken between day 5 and day 10

Population: The analysis population consisted of the PKAS.

Drug concentration was derived from the stool samples collected.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=74 Participants 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.	Vancomycin n=47 Participants 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.	Fidaxomicin Tablets n=27 Participants Participants received fidaxomicin tablets formulation.
Fecal Concentrations of Fidaxomicin	2685.56 μg/g Standard Deviation 2476.92	2969.87 μg/g Standard Deviation 2713.58	2190.63 μg/g Standard Deviation 1948.68

SECONDARY outcome

Timeframe: Within 24 hours of a dose taken between day 5 and day 10

Population: The analysis population consisted of the PKAS.

Drug concentration was derived from the stool samples collected.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=73 Participants 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.	Vancomycin n=46 Participants 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.	Fidaxomicin Tablets n=27 Participants Participants received fidaxomicin tablets formulation.
Fecal Concentrations of Metabolite OP-1118	889.23 μg/g Standard Deviation 817.83	789.15 μg/g Standard Deviation 728.58	1059.73 μg/g Standard Deviation 941.04

SECONDARY outcome

Timeframe: Within 24 hours of a dose taken between day 5 and day 10

Population: The analysis population consisted of the PKAS.

Drug concentration was derived from the stool samples collected.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=72 Participants 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.	Vancomycin n=45 Participants 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.	Fidaxomicin Tablets n=27 Participants Participants received fidaxomicin tablets formulation.
MPRconc Within 24 Hours of a Dose	0.43 ratio Standard Deviation 0.31	0.32 ratio Standard Deviation 0.19	0.63 ratio Standard Deviation 0.38

SECONDARY outcome

Timeframe: Days 1 and 7

Population: The analysis population consisted of the FAS.

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.

Outcome measures

Outcome measures
Measure	Fidaxomicin n=67 Participants 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.	Vancomycin n=30 Participants 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.	Fidaxomicin Tablets Participants received fidaxomicin tablets formulation.
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 1 Awful	4 Participants	5 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 1 Poor	6 Participants	3 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 1 Fair	13 Participants	6 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 1 Good	19 Participants	7 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 1 Excellent	13 Participants	4 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 1 Missing	12 Participants	5 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 7 Awful	2 Participants	3 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 7 Poor	5 Participants	5 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 7 Fair	8 Participants	5 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 7 Good	21 Participants	9 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 7 Excellent	16 Participants	3 Participants	—
Acceptance of Formulation (Palatability Assessment) in All Participants at First Administration of Study Drug and at Day 7 Day 7 Missing	15 Participants	5 Participants	—

Adverse Events

Fidaxomicin

Serious events: 24 serious events

Other events: 36 other events

Deaths: 3 deaths

Vancomycin

Serious events: 12 serious events

Other events: 21 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Fidaxomicin n=98 participants at risk 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.	Vancomycin n=44 participants at risk 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.
Gastrointestinal disorders Abdominal pain	5.1% 5/98 • Number of events 6 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.	20.5% 9/44 • Number of events 11 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.
Gastrointestinal disorders Constipation	5.1% 5/98 • Number of events 6 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.	2.3% 1/44 • Number of events 1 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.
Gastrointestinal disorders Diarrhoea	7.1% 7/98 • Number of events 7 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.	9.1% 4/44 • Number of events 5 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.
Gastrointestinal disorders Vomiting	7.1% 7/98 • Number of events 8 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.	13.6% 6/44 • Number of events 8 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.
General disorders Pyrexia	11.2% 11/98 • Number of events 18 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.	18.2% 8/44 • Number of events 11 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.
Infections and infestations Oral candidiasis	3.1% 3/98 • Number of events 3 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.	6.8% 3/44 • Number of events 3 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.
Nervous system disorders Headache	8.2% 8/98 • Number of events 11 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.	0.00% 0/44 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.
Skin and subcutaneous tissue disorders Pruritus	3.1% 3/98 • Number of events 3 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.	6.8% 3/44 • Number of events 3 • From the first dose of study drug administration up to 30 days after EOT (up to day 40) The total number of deaths (all causes) includes deaths reported after time frame above.

Additional Information

Clinical Trial Disclosure

Astellas Pharma Global Development, Inc.

Phone: 800-888-7704

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Publication restrictions are in place

Restriction type: OTHER