Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia

• Sponsor: Basilea Pharmaceutica (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03439124
• Collaborator: (none)
• Enrollment: 138
• Locations: 19
• Arms: 2
• Actual Duration (Months): 27.6
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This was a study of the safety and efficacy of ceftobiprole medocaril compared with intravenous (IV) standard-of-care cephalosporin treatment with or without vancomycin in pediatric patients with either hospital-acquired bacterial pneumonia (HAP) or community-acquired bacterial pneumonia (CAP) requiring hospitalization, and requiring intravenous (IV) antibiotic therapy.

Condition or Disease	Intervention/Treatment	Phase
Community-acquired Pneumonia (CAP); Hospital-acquired Pneumonia (HAP)	Drug: ceftobiprole medocaril; Drug: IV standard-of-care cephalosporin	Phase 3

Detailed Description

This was a randomized, investigator-blind, active-controlled multi-center study to evaluate the safety, tolerability, pharmacokinetics and efficacy of ceftobiprole medocaril compared with IV standard-of-care cephalosporin treatment with or without vancomycin in pediatric patients aged 3 months to less than 18 years with HAP or CAP requiring hospitalization and therapy with IV antibiotics. Randomization was stratified by four age groups (3 months to < 2 years; 2 years to < 6 years; 6 years to < 12 years; 12 years to < 18 years), and by diagnosis of HAP or CAP.

Study Design

• Study Type: Interventional
• Actual Enrollment: 138 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Randomized, Investigator-blind, Active-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Ceftobiprole Versus Intravenous Standard-of-care Cephalosporin Treatment With or Without Vancomycin in Pediatric Patients Aged From 3 Months to Less Than 18 Years With Hospital-acquired Pneumonia or Community-acquired Pneumonia Requiring Hospitalisation
• Actual Study Start Date: Nov 27, 2017
• Actual Primary Completion Date: Mar 16, 2020
• Actual Study Completion Date: Mar 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: ceftobiprole medocaril; Ceftobiprole medocaril was administered at age-adjusted doses (10, 15 or 20 mg/kg) and infusion durations (2 or 4 hours) every 8 hours. The maximum dose, regardless of body weight, was 500 mg ceftobiprole every 8 hours (maximum total daily dose of 1500 mg ceftobiprole). After a minimum of 3 days of IV treatment, patients with sufficient improvement in disease signs and symptoms could be switched to an age-appropriate oral antibiotic to complete a total minimum of 7 days and a total maximum of 14 days' antibiotic treatment.; Other Names: ceftobiprole
Active Comparator: IV standard-of-care cephalosporin 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 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.	Drug: IV standard-of-care cephalosporin; Ceftriaxone was administered at 50 to 80 mg/kg IV as a single daily dose, up to a maximum dose of 2 g/day. The actual dose of ceftriaxone within this dose range was determined by the blinded investigator prior to first study drug administration and was not modified during subsequent study days. After a minimum of 3 days of IV treatment, patients with sufficient improvement in disease signs and symptoms could be switched to an age-appropriate oral antibiotic to complete a total minimum of 7 days and a total maximum of 14 days' antibiotic treatment. At the discretion of the blinded investigator, patients received vancomycin at a dose of 10 to 15 mg/kg IV every 6 hours, up to a maximum dose of 2 g/day, in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.

Outcome Measures

Primary Outcome Measures

1. Adverse Events [Analysis of AEs assessed during the first 3 days of IV therapy and while on IV, a median of 7 days]

   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.

Secondary Outcome Measures

1. Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT) [At the test-of-cure (TOC) visit]

   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.

2. Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population [At the TOC visit]

   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.

3. Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population [At Day 4]

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

4. Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population [At Day 4]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Months to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male of female aged 3 months to < 18 years with a body weight of at least 5 kg

• Diagnosis of either hospital-acquired pneumonia or community-acquired pneumonia requiring hospitalization and administration of IV antibiotic therapy

• New or progressive imaging findings consistent with bacterial pneumonia

• Requirement for IV antibacterial treatment for pneumonia

• Other inclusion criteria may apply

Exclusion Criteria:

• Known resistance of the causative pathogen to ceftobiprole or IV standard-of-care cephalosporin treatment (± vancomycin)

• On mechanical ventilation

• Chest trauma with severe lung contusion or flail chest

• Acute respiratory distress syndrome

• Empyema or lung abscess

• Anatomical bronchial obstruction

• Active or currently treated pulmonary tuberculosis

• Atypical bacterial pneumonia, or viral pneumonia without bacterial superinfection, or need for antibiotic coverage with a macrolide

• Pertussis, chemical pneumonitis, or cystic fibrosis

• Severe immunodeficiency

• Significant laboratory abnormalities including: Hematocrit <20%; absolute neutrophil count <0.5x10⁹/L; platelet count <50x10⁹/L; alanine aminotransferase, aspartate aminotransferase, or bilirubin >5 times the age-specific upper limit of normal;

• Creatinine clearance <50 mL/min/1.73 m²

• Use of systemic antimicrobial therapy for more than 24 hours in the 48 hours before randomization

• History of a previous clinically-relevant hypersensitivity or serious adverse reaction to beta lactam antibiotics or to vancomycin

• Poorly controlled seizure disorder

• Other exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"	Pleven		Bulgaria	5800
2	University Multiprofile Hospital for Active Treatment "Sveti Georgi"	Plovdiv		Bulgaria	4002
3	Multiprofile Hospital for Active Treatment	Ruse		Bulgaria	7002
4	University Multiprofile Hospital for Active Treatment "Aleksandrovska"	Sofia		Bulgaria	1431
5	Amtel Hospital First Clinical LLC	Tbilisi		Georgia	0144
6	LTD High Technology Medical Center University Clinic	Tbilisi		Georgia	0144
7	JSC Evex Hospitals 1	Tbilisi		Georgia	0159
8	JSC Evex Hospitals 2	Tbilisi		Georgia	0159
9	Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic	Tbilisi		Georgia	0159
10	Ltd Tbilisi Pediatric Private Clinic	Tbilisi		Georgia	0191
11	Principal SMO Ltd.	Baja		Hungary	6500
12	Semmelweis University	Budapest		Hungary	1094
13	Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases	Budapest		Hungary	1097
14	Bekes County Central Hospital	Gyula		Hungary	5700
15	Kanizsai Dorottya Hospital	Nagykanizsa		Hungary	8800
16	Fejer County St. Gyorgy University Teaching Hospital	Szekesfehervar		Hungary	8000
17	Torokbalint Pulmonology Institute	Torokbalint		Hungary	2045
18	Alessandrescu-Rusescu National Institute for Mother and Child Health	Bucharest		Romania	020395
19	Sf. Maria" Children's Emergency Clinical Hospital	Iaşi		Romania	700309

Sponsors and Collaborators

• Basilea Pharmaceutica

Investigators

• Study Director: Marc Engelhardt, MD, Basilea Pharmaceutica

Study Documents (Full-Text)

• Study Protocol - Nov 29, 2018
• Statistical Analysis Plan - Mar 2, 2020

More Information

Publications

None provided.

• Responsible Party: Basilea Pharmaceutica
• ClinicalTrials.gov Identifier: NCT03439124
• Other Study ID Numbers: BPR-PIP-002
• First Posted: Feb 20, 2018
• Last Update Posted: Mar 9, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Pneumonia; Healthcare-Associated Pneumonia; Cephalosporins; Ceftobiprole; Ceftobiprole medocaril

Study Results

Participant Flow

Pre-assignment Detail	All 138 randomized patients received treatment

Arm/Group Title	Ceftobiprole Medocaril	IV Standard-of-care Cephalosporin
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	94	44
COMPLETED	90	44
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Ceftobiprole Medocaril	IV Standard-of-care Cephalosporin	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	94	44	138
Age (Count of Participants)
<=18 years	94 100%	44 100%	138 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	6.81	6.95	6.86
Sex: Female, Male (Count of Participants)
Female	41 43.6%	23 52.3%	64 46.4%
Male	53 56.4%	21 47.7%	74 53.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 2.3%	1 0.7%
White	94 100%	43 97.7%	137 99.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Infection type (Count of Participants)
Hospital-acquired pneumonia	5 5.3%	3 6.8%	8 5.8%
Community-acquired pneumonia	89 94.7%	41 93.2%	130 94.2%

Outcome Measures

1. Primary Outcome

Title	Adverse Events
Description	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.
Time Frame	Analysis of AEs assessed during the first 3 days of IV therapy and while on IV, a median of 7 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ceftobiprole Medocaril	IV Standard-of-care Cephalosporin
Arm/Group Description	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.	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.
Measure Participants	94	44
Non-Serious TEAE	10 10.6%	5 11.4%
Serious TEAE	1 1.1%	0 0%
TEAE leading to death	0 0%	0 0%
No TEAE	83 88.3%	39 88.6%
Non-Serious TEAE	17 18.1%	8 18.2%
Serious TEAE	2 2.1%	0 0%
TEAE leading to death	0 0%	0 0%
No TEAE	75 79.8%	36 81.8%

2. Secondary Outcome

Title	Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT)
Description	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.
Time Frame	At the test-of-cure (TOC) visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ceftobiprole Medocaril	IV Standard-of-care Cephalosporin
Arm/Group Description	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.	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.
Measure Participants	94	44
Count of Participants [Participants]	85 90.4%	43 97.7%

3. Secondary Outcome

Title	Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population
Description	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.
Time Frame	At the TOC visit

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ceftobiprole Medocaril	IV Standard-of-care Cephalosporin
Arm/Group Description	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.	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.
Measure Participants	88	41
Count of Participants [Participants]	80 85.1%	41 93.2%

4. Secondary Outcome

Title	Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population
Description	Comparison of early clinical response rates in the ITT population between ceftobiprole and the comparator at Day 4.
Time Frame	At Day 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ceftobiprole Medocaril	IV Standard-of-care Cephalosporin
Arm/Group Description	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.	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.
Measure Participants	94	44
Count of Participants [Participants]	90 95.7%	41 93.2%

5. Secondary Outcome

Title	Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population
Description	Comparison of early clinical response rates in the CE population between ceftobiprole and the comparator at Day 4.
Time Frame	At Day 4

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ceftobiprole Medocaril	IV Standard-of-care Cephalosporin
Arm/Group Description	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.	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.
Measure Participants	88	41
Count of Participants [Participants]	84 89.4%	39 88.6%

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	Ceftobiprole Medocaril		IV Standard-of-care Cephalosporin
Arm/Group Description	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.		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.
All Cause Mortality
	Ceftobiprole Medocaril		IV Standard-of-care Cephalosporin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/94 (0%)		0/44 (0%)
Serious Adverse Events
	Ceftobiprole Medocaril		IV Standard-of-care Cephalosporin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/94 (7.4%)		2/44 (4.5%)
Gastrointestinal disorders
Vomiting	1/94 (1.1%)	1	0/44 (0%)	0
Immune system disorders
Hypersensitivity	1/94 (1.1%)	1	0/44 (0%)	0
Infections and infestations
Pneumonia	3/94 (3.2%)	3	0/44 (0%)	0
Bronchitis	0/94 (0%)	0	1/44 (2.3%)	1
Pharyngitis streptococcal	1/94 (1.1%)	1	0/44 (0%)	0
Tonsillitis streptococcal	1/94 (1.1%)	1	0/44 (0%)	0
Nervous system disorders
Seizure like phenomena	0/94 (0%)	0	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/94 (1.1%)	1	0/44 (0%)	0
Pleurisy	1/94 (1.1%)	1	0/44 (0%)	0
Other (Not Including Serious) Adverse Events
	Ceftobiprole Medocaril		IV Standard-of-care Cephalosporin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/94 (8.5%)		5/44 (11.4%)
Gastrointestinal disorders
Vomiting	6/94 (6.4%)	6	1/44 (2.3%)	1
Diarrhoea	2/94 (2.1%)	2	4/44 (9.1%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.