Trial Outcomes & Findings for Bezlotoxumab (MK-6072) Versus Placebo in Children With Clostridium Difficile Infection (CDI) (MK-6072-001) (NCT NCT03182907)

Last Updated: 2023-07-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

148 participants

Primary outcome timeframe

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

Results posted on

2023-07-27

Participant Flow

148 participants were randomized in the study of which 143 participants received study intervention and were used for safety analysis.

Participant milestones

Participant milestones
Measure	Bezlotoxumab Participants received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Placebo Participants received placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Overall Study STARTED	111	37
Overall Study Treated	107	36
Overall Study COMPLETED	103	35
Overall Study NOT COMPLETED	8	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Bezlotoxumab Participants received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Placebo Participants received placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Overall Study Death	3	0
Overall Study Protocol Violation	4	0
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Parent/Guardian	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bezlotoxumab n=111 Participants Participants received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Placebo n=37 Participants Participants received placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Total n=148 Participants Total of all reporting groups
Age, Continuous	9.2 years STANDARD_DEVIATION 5.4 • n=5 Participants	9.3 years STANDARD_DEVIATION 5.3 • n=7 Participants	9.2 years STANDARD_DEVIATION 5.3 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	18 Participants n=7 Participants	69 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	19 Participants n=7 Participants	79 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=5 Participants	9 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=5 Participants	27 Participants n=7 Participants	99 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	87 Participants n=5 Participants	32 Participants n=7 Participants	119 Participants n=5 Participants
Race (NIH/OMB) More than one race	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=36 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=54 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Area Under the Concentration-Time Curve of Bezlotoxumab From Time 0 to Infinity (AUC0-inf)	56100 hr*ug/mL Interval 49400.0 to 63700.0	43200 hr*ug/mL Interval 38900.0 to 47900.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=107 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=36 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Percentage of Participants Who Experienced an Adverse Event (AE)	88.8 Percentage of participants	94.4 Percentage of participants

PRIMARY outcome

Timeframe: 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 who discontinued study due to AEs in the bezlotoxumab and placebo groups were presented.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=107 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=36 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Percentage of Participants Who Discontinued Study Due to an AE	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=98 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=34 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Percentage of Participants Who Had a Clostridium Difficile Infection (CDI) Recurrence	11.2 Percentage of participants	14.7 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=104 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=35 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Percentage of Participants Who Had a Sustained Clinical Response (SCR)	83.7 Percentage of participants	82.9 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=91 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=33 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Percentage of High-Risk Participants Who Experienced a CDI Recurrence	12.1 Percentage of participants	15.2 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=97 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=34 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Percentage of High-Risk Participants Who Experienced a SCR	82.5 Percentage of participants	82.4 Percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 24 hours after infusion on Day 1

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

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.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=107 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=36 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Percentage of Participants Who Experienced One or More Infusion Related Reaction	0.93 Percentage of participants	2.78 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Bezlotoxumab: Cohort 1 (12 to <18 Years Age) n=44 Participants Participants aged 12 to \<18 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Bezlotoxumab: Cohort 2 (1 to <12years of Age) n=62 Participants Participants aged 1 to \<12 years of age received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Percentage of Participants Who Had Positive Antibodies to Bezlotoxumab	2.4 Percentage of participants	1.7 Percentage of participants

Adverse Events

Bezlotoxumab

Serious events: 57 serious events

Other events: 65 other events

Deaths: 6 deaths

Placebo

Serious events: 29 serious events

Other events: 28 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts and manuscripts regarding this study prior to submission for publication. This will allow the SPONSOR to protect the proprietary information prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	Bezlotoxumab n=107 participants at risk Participants received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.	Placebo n=36 participants at risk Participants received placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
Blood and lymphatic system disorders Anaemia	7.5% 8/107 • Number of events 8 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	16.7% 6/36 • Number of events 10 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Blood and lymphatic system disorders Febrile neutropenia	0.93% 1/107 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Blood and lymphatic system disorders Leukopenia	3.7% 4/107 • Number of events 4 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Blood and lymphatic system disorders Neutropenia	6.5% 7/107 • Number of events 7 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Blood and lymphatic system disorders Thrombocytopenia	6.5% 7/107 • Number of events 8 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	8.3% 3/36 • Number of events 3 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Gastrointestinal disorders Abdominal pain	12.1% 13/107 • Number of events 28 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	16.7% 6/36 • Number of events 10 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Gastrointestinal disorders Constipation	6.5% 7/107 • Number of events 11 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Gastrointestinal disorders Diarrhoea	7.5% 8/107 • Number of events 9 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	13.9% 5/36 • Number of events 14 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Gastrointestinal disorders Nausea	6.5% 7/107 • Number of events 10 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	11.1% 4/36 • Number of events 5 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Gastrointestinal disorders Stomatitis	7.5% 8/107 • Number of events 10 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Gastrointestinal disorders Vomiting	13.1% 14/107 • Number of events 16 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	22.2% 8/36 • Number of events 12 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
General disorders Pyrexia	14.0% 15/107 • Number of events 22 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	22.2% 8/36 • Number of events 12 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Infections and infestations Bacteraemia	0.00% 0/107 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Infections and infestations Oral herpes	4.7% 5/107 • Number of events 5 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 4 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Infections and infestations Rhinitis	1.9% 2/107 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 3 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Infections and infestations Upper respiratory tract infection	0.93% 1/107 • Number of events 1 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Injury, poisoning and procedural complications Transfusion reaction	0.00% 0/107 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Investigations Alanine aminotransferase increased	8.4% 9/107 • Number of events 12 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	0.00% 0/36 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Investigations Aspartate aminotransferase increased	7.5% 8/107 • Number of events 8 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	0.00% 0/36 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Investigations C-reactive protein increased	3.7% 4/107 • Number of events 4 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 3 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Metabolism and nutrition disorders Decreased appetite	0.93% 1/107 • Number of events 1 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Metabolism and nutrition disorders Hypokalaemia	7.5% 8/107 • Number of events 9 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	16.7% 6/36 • Number of events 6 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 2/107 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	8.3% 3/36 • Number of events 3 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Nervous system disorders Headache	14.0% 15/107 • Number of events 22 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	19.4% 7/36 • Number of events 8 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Respiratory, thoracic and mediastinal disorders Cough	2.8% 3/107 • Number of events 4 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.93% 1/107 • Number of events 1 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/107 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/107 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/107 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Skin and subcutaneous tissue disorders Urticaria	0.93% 1/107 • Number of events 1 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Skin and subcutaneous tissue disorders Vancomycin infusion reaction	0.93% 1/107 • Number of events 1 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.	5.6% 2/36 • Number of events 2 • Up to approximately 14 months All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.