Bezlotoxumab (MK-6072) Versus Placebo in Children With Clostridium Difficile Infection (CDI) (MK-6072-001)

Blood samples were collected at specified intervals for the determination of AUC0-inf. AUC0-inf was defined as the area under the concentration-time curve of bezlotoxumab from time zero to infinity. Per protocol, AUC0-inf of bezlotoxumab was determined for each age cohort.

Time frame: Day 1 (2 hours postdose), Days 10, 29, 57, and 85

Population: The analysis population included all participants who received bezlotoxumab, had at least 4 postdose AUC0-inf samples and complied with the protocol.

An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality. Per protocol, percentage of participants who discontinued study due to AEs in the bezlotoxumab and placebo groups were presented.

Time frame: Up to approximately 12 weeks

Population: The analysis population included all participants who received study intervention.

An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality. Per protocol, percentage of participants with AEs in the bezlotoxumab and placebo groups were presented.

Time frame: Up to approximately 12 weeks

Population: The analysis population included all participants who received study intervention.

CDI recurrence was defined as diarrhea recurrence (new diarrhea episode after ICR defined by change in normal bowel habits for ≥2 days with watery diarrhea or at least 6 UBMs within 48-hours) with positive stool test for C. difficile toxin for which participant, in investigator's opinion, requires and receives ABD for CDI. High-risk was meeting ≥1 criteria at/before randomization: a) was immunocompromised b) had ≥1 CDI episode prior to baseline episode c) had severe CDI baseline episode d) had C. difficile ribotype027 in stool at baseline CDI episode e) received ≥1 systemic ABD known to increase CDI risk. Per protocol, percentage of high-risk participants who experienced a CDI recurrence in the bezlotoxumab and placebo groups were presented.

Time frame: Up to approximately 12 Weeks

Population: The analysis population included all participants who received study intervention, had positive local stool for C. difficile toxin, were taking ABD for CDI on infusion day, achieved ICR of baseline CDI, and were at high-risk of CDI recurrence.

SCR was ICR of baseline CDI episode (improvement in number and character of bowel movements and doesn't require further CDI therapy within 2 days after completion of up to 21 days of ABD for CDI) and no CDI recurrence (diarrhea recurrence with positive stool test for C. difficile toxin, for which participant, in investigator's opinion, requires and receives ABD for CDI). High-risk was meeting ≥1 criteria: a) was immunocompromised b) had ≥1 episodes of CDI prior to baseline episode c) had severe CDI baseline episode d) had C. difficile ribotype027 in stool at baseline CDI episode e) received ≥1 systemic ABD known to increase CDI risk. Per protocol, percentage of high-risk participants who had SCR in bezlotoxumab and placebo groups were presented.

Time frame: Up to approximately 12 Weeks

Population: The analysis population included all participants who received study intervention, had positive local stool for C. difficile toxin, were taking protocol-defined ABD for CDI on the day of infusion, and were at high risk of CDI recurrence.

Infusion related reaction included events meeting any of the 3 criteria: 1) acute onset of an illness involving skin, mucosal tissue, or both and at least 1 of the following: respiratory compromise, reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 2) two or more of the following after onset of study infusion: involving skin-mucosal tissue, respiratory compromise, reduced BP or associated symptoms, or persistent gastrointestinal symptoms 3) reduced BP after onset of infusion or \>30% decrease in systolic BP from baseline. Per protocol, percentage of participants experiencing 1 or more infusion-related reactions within 24 hours following the start of study medication infusion were reported.

Time frame: Up to approximately 24 hours after infusion on Day 1

Population: The analysis population included all participants who received study intervention.

CDI recurrence was defined as diarrhea recurrence (new episode of diarrhea after initial clinical response \[ICR\] as defined by a change in normal bowel habits for ≥2 days with either watery diarrhea or at least 6 unformed bowel movements \[UBMs\] within 48-hours) associated with a positive stool test for C. difficile toxin, and for which the participant, in the investigator's opinion, requires and receives ABD treatment for CDI. Per protocol, percentage of participants who had a CDI recurrence in the bezlotoxumab and placebo groups were reported.

Time frame: Up to approximately 12 Weeks

Population: The analysis population included all participants who received any amount of study intervention, had positive local stool for C. difficile toxin, were taking protocol-defined ABD treatment for CDI on the day of infusion, and achieved an ICR of baseline CDI.

SCR was defined as the ICR of baseline CDI episode (improvement in number and character of bowel movements and doesn't require further CDI therapy within 2 days after completion of up to 21 days of ABD treatment for CDI) and no CDI recurrence (diarrhea recurrence associated with a positive stool test for C. difficile toxin, and for which the participant, in investigator's opinion, requires and receives ABD for CDI). Per protocol, percentage of participants who had a SCR in bezlotoxumab and placebo groups were presented.

Time frame: Up to approximately 12 Weeks

Population: The analysis population included all participants who received any amount of study intervention, had positive local stool for C. difficile toxin, and were taking protocol-defined ABD treatment for CDI on the day of infusion.

Blood samples were collected to determine antibodies to bezlotoxumab. Per protocol, percentage of participants with treatment-emergent positive antibodies to bezlotoxumab following single infusion of bezlotoxumab were reported for each age cohort.

Time frame: Up to approximately 12 Weeks

Population: The analysis population included all participants who received any amount of bezlotoxumab, had a positive local stool for C. difficile toxin, were taking protocol-defined ABD drug treatment for CDI on the day of infusion, and achieved an ICR of baseline CDI.