Trial Outcomes & Findings for Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia (NCT NCT03439124)

NCT ID: NCT03439124

Last Updated: 2023-05-12

Results Overview

Reported are adverse events (AEs) during the first 3 days of IV therapy and while patients were on IV therapy irrespective of when they switched to oral antibiotic treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 138 participants
• Primary outcome timeframe: Analysis of AEs assessed during the first 3 days of IV therapy and while on IV, a median of 7 days
• Results posted on: 2023-05-12

Participant Flow

All 138 randomized patients received treatment

Participant milestones

Measure	Ceftobiprole Medocaril Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin Ceftriaxone was used as standard-of-care cephalosporin for the treatment of community-acquired pneumonia (CAP). It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of hospital-acquired pneumonia (HAP). It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA). At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Overall Study STARTED	94	44
Overall Study COMPLETED	90	44
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Measure	Ceftobiprole Medocaril Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin Ceftriaxone was used as standard-of-care cephalosporin for the treatment of community-acquired pneumonia (CAP). It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of hospital-acquired pneumonia (HAP). It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA). At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Overall Study Adverse Event	2	0
Overall Study Lost to Follow-up	1	0
Overall Study Other reasons	1	0

Baseline Characteristics

Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia

Baseline characteristics by cohort

Measure	Ceftobiprole Medocaril n=94 Participants Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin n=44 Participants Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including MRSA. At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.	Total n=138 Participants Total of all reporting groups
Age, Categorical <=18 years	94 Participants n=5 Participants	44 Participants n=7 Participants	138 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	6.81 years n=5 Participants	6.95 years n=7 Participants	6.86 years n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	23 Participants n=7 Participants	64 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	21 Participants n=7 Participants	74 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	94 Participants n=5 Participants	43 Participants n=7 Participants	137 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Infection type Hospital-acquired pneumonia	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Infection type Community-acquired pneumonia	89 Participants n=5 Participants	41 Participants n=7 Participants	130 Participants n=5 Participants

PRIMARY outcome

Timeframe: Analysis of AEs assessed during the first 3 days of IV therapy and while on IV, a median of 7 days

Population: Safety population: all randomized patients who received at least one dose of study drug, analyzed according to the first treatment actually received.

Reported are adverse events (AEs) during the first 3 days of IV therapy and while patients were on IV therapy irrespective of when they switched to oral antibiotic treatment.

Outcome measures

Measure	Ceftobiprole Medocaril n=94 Participants Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin n=44 Participants Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including MRSA. At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Adverse Events First 3 days of IV therapy · Non-Serious TEAE	10 Participants	5 Participants
Adverse Events First 3 days of IV therapy · Serious TEAE	1 Participants	0 Participants
Adverse Events First 3 days of IV therapy · TEAE leading to death	0 Participants	0 Participants
Adverse Events First 3 days of IV therapy · No TEAE	83 Participants	39 Participants
Adverse Events While on IV therapy · Non-Serious TEAE	17 Participants	8 Participants
Adverse Events While on IV therapy · Serious TEAE	2 Participants	0 Participants
Adverse Events While on IV therapy · TEAE leading to death	0 Participants	0 Participants
Adverse Events While on IV therapy · No TEAE	75 Participants	36 Participants

SECONDARY outcome

Timeframe: At the test-of-cure (TOC) visit

Population: Intent-to-treat (ITT) population: all randomized patients, analyzed by treatment assigned.

Comparison of clinical cure rates (signs and symptoms of pneumonia normalized or improved such that no further antibiotic therapy was necessary, and stabilization or improvement of chest X-ray findings if these were available) in the ITT population between ceftobiprole and the comparator at the TOC visit.

Outcome measures

Measure	Ceftobiprole Medocaril n=94 Participants Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin n=44 Participants Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including MRSA. At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT)	85 Participants	43 Participants

SECONDARY outcome

Timeframe: At the TOC visit

Population: Clinically Evaluable (CE) population: all patients who had a valid clinical outcome assessment at TOC and no major protocol deviations such as non-study antibiotic therapies.

Comparison of clinical cure rates (signs and symptoms of pneumonia normalized or improved such that no further antibiotic therapy was necessary, and stabilization or improvement of chest X-ray findings if these were available) in the CE population between ceftobiprole and the comparator at the TOC visit.

Outcome measures

Measure	Ceftobiprole Medocaril n=88 Participants Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin n=41 Participants Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including MRSA. At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population	80 Participants	41 Participants

SECONDARY outcome

Timeframe: At Day 4

Population: Intent-to-treat (ITT) population: all randomized patients, analyzed by treatment assigned.

Comparison of early clinical response rates in the ITT population between ceftobiprole and the comparator at Day 4.

Outcome measures

Measure	Ceftobiprole Medocaril n=94 Participants Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin n=44 Participants Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including MRSA. At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population	90 Participants	41 Participants

SECONDARY outcome

Timeframe: At Day 4

Population: Clinically Evaluable (CE) population: all patients who had a valid clinical outcome assessment at TOC and no major protocol deviations such as non-study antibiotic therapies.

Comparison of early clinical response rates in the CE population between ceftobiprole and the comparator at Day 4.

Outcome measures

Measure	Ceftobiprole Medocaril n=88 Participants Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin n=41 Participants Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including MRSA. At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population	84 Participants	39 Participants

Adverse Events

Ceftobiprole Medocaril

Serious events: 7 serious events

Other events: 8 other events

Deaths: 0 deaths

IV Standard-of-care Cephalosporin

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ceftobiprole Medocaril n=94 participants at risk Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin n=44 participants at risk Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including MRSA. At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.1% 1/94 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	0.00% 0/44 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Respiratory, thoracic and mediastinal disorders Pleurisy	1.1% 1/94 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	0.00% 0/44 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Immune system disorders Hypersensitivity	1.1% 1/94 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	0.00% 0/44 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Nervous system disorders Seizure like phenomena	0.00% 0/94 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	2.3% 1/44 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Gastrointestinal disorders Vomiting	1.1% 1/94 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	0.00% 0/44 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Infections and infestations Pneumonia	3.2% 3/94 • Number of events 3 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	0.00% 0/44 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Infections and infestations Bronchitis	0.00% 0/94 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	2.3% 1/44 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Infections and infestations Pharyngitis streptococcal	1.1% 1/94 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	0.00% 0/44 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Infections and infestations Tonsillitis streptococcal	1.1% 1/94 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	0.00% 0/44 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.

Other adverse events

Measure	Ceftobiprole Medocaril n=94 participants at risk Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	IV Standard-of-care Cephalosporin n=44 participants at risk Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including MRSA. At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Gastrointestinal disorders Vomiting	6.4% 6/94 • Number of events 6 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	2.3% 1/44 • Number of events 1 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.
Gastrointestinal disorders Diarrhoea	2.1% 2/94 • Number of events 2 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.	9.1% 4/44 • Number of events 4 • Relevant worsening of a patient's status after informed consent (before start of first study-drug infusion) was recorded in medical history. From start of first dosing to and including the last follow-up visit, 28 to 35 days after end-of-treatment, such worsening was recorded as an AE. Once an AE was detected, it was proactively followed up at each visit (or more frequently if necessary) for any changes in severity, relationship to the study drug, interventions required for treatment, and the event's outcome. Serious adverse events (SAEs) were to be additionally reported and recorded on SAE report forms.

Additional Information

Project Physician

Basilea Pharmaceutica International Ltd.

Phone: +41 79 701 0551

Email: marc.engelhardt@basilea.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60