Pharmacokinetics and Safety of Ceftobiprole in Neonates and Infants up to 3 Months Treated With Systemic Antibiotics

• Sponsor: Basilea Pharmaceutica (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02527681
• Collaborator: (none)
• Enrollment: 15
• Locations: 14
• Arm: 1
• Actual Duration (Months): 39.1
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study characterized the pharmacokinetics and safety of a single dose of ceftobiprole in neonates and infants aged ≤ 3 months.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Infections	Drug: Ceftobiprole medocaril	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study to Evaluate the Single-dose Pharmacokinetics and Safety of Ceftobiprole in Neonate and Infant Subjects Aged up to 3 Months Undergoing Treatment With Systemic Antibiotics
• Actual Study Start Date: Nov 22, 2016
• Actual Primary Completion Date: Feb 25, 2020
• Actual Study Completion Date: Feb 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ceftobiprole Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for intravenous 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 as a single intravenous infusion, with a bodyweight-adjusted volume, at a constant rate over 4 hours. The ceftobiprole dose was 7.5 mg/kg, which corresponds to 10.0 mg ceftobiprole medocaril.; Other Names: ceftobiprole

Outcome Measures

Primary Outcome Measures

1. Cmax [Blood samples for pharmacokinetic (PK) analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.]

   The maximum observed plasma concentration (Cmax)

2. Tmax [Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.]

   The time of maximum observed plasma concentration (Tmax)

3. AUC0-last [Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.]

   The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-last)

4. T>MIC of 4 mg/L [Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.]

   The duration of time after dose for which free-drug concentrations remained above a value of 4 mg/L (T>MIC of 4 mg/L)

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 3 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Neonates and infants ≤3 months, with gestational age ≥28 weeks

• Documented or presumed (or at risk of) bacterial infections, and currently receiving antibiotic treatment

• Expected to survive beyond the first 7 days after enrollment

• Sufficient vascular access to receive study drug, and to allow blood sampling at a site separate from the study drug infusion site

• Parent's / legally acceptable representative's informed consent to participate in the study

Exclusion Criteria:

• Major birth defect or malformation syndrome

• Proven presence of an immunodeficiency

• HIV or other congenital viral or fungal infection

• Significant laboratory abnormalities including: hematocrit <20%; absolute neutrophil count <0.5x10⁹/L; platelet count < 50x10⁹/L; alanine aminotransferase or aspartate aminotransferase >3 times the age-specific upper limit of normal

• Impaired renal function or known significant renal disease

• Any condition which would make the subject or caregiver, in the opinion of the investigator, unsuitable for the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loma Linda University Medical Center	Loma Linda	California	United States	92354
2	University of Southern California	Los Angeles	California	United States	90089
3	University of California Los Angeles	Los Angeles	California	United States	90095
4	Beacon Children's Hospital	South Bend	Indiana	United States	46601
5	Norton Children's Hospital	Louisville	Kentucky	United States	40202
6	Duke University Hospital	Durham	North Carolina	United States	27705
7	University of Pittsburgh Medical Center Cancer Center at Magee-Womens Hospital	Pittsburgh	Pennsylvania	United States	15224
8	The University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
9	West Virginia University School of Medicine	Morgantown	West Virginia	United States	26506-9214
10	UZ Leuven	Leuven		Belgium
11	Klinikum der Universität München	Munich		Germany
12	Children Clinical University Hospital	Riga		Latvia
13	Vilnius University Children's Hospital	Vilnius		Lithuania
14	University Children's Hospital of Kraków	Kraków		Poland

Sponsors and Collaborators

• Basilea Pharmaceutica

Investigators

• Study Director: Marc Engelhardt, MD, Basilea Pharmaceutica

Study Documents (Full-Text)

• Study Protocol - Mar 21, 2019
• Statistical Analysis Plan - Aug 17, 2020

More Information

Publications

None provided.

• Responsible Party: Basilea Pharmaceutica
• ClinicalTrials.gov Identifier: NCT02527681
• Other Study ID Numbers: BPR-PIP-001; 2013-004614-18
• First Posted: Aug 19, 2015
• Last Update Posted: Mar 9, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Bacterial Infections; Ceftobiprole; Ceftobiprole medocaril; Cephalosporins

Study Results

Participant Flow

Pre-assignment Detail	Subjects with documented or presumed bacterial infection receiving standard-of-care antibiotic treatment were screened.

Arm/Group Title	Ceftobiprole ITT/Safety Population
Arm/Group Description	All subjects who received any quantity of study drug.
Period Title: Overall Study
STARTED	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ceftobiprole ITT/Safety Population
Arm/Group Description	All subjects who received any quantity of study drug.
Overall Participants	15
Age (Count of Participants)
<=18 years	15 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	13
Sex: Female, Male (Count of Participants)
Female	5 33.3%
Male	10 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	1 6.7%
Black or African American	1 6.7%
White	13 86.7%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Cmax
Description	The maximum observed plasma concentration (Cmax)
Time Frame	Blood samples for pharmacokinetic (PK) analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ceftobiprole PK Population
Arm/Group Description	All subjects who received study drug and had adequate samples for determination of time-plasma concentration profiles of ceftobiprole.
Measure Participants	13
Median (Full Range) [μg/mL]	11.2

2. Primary Outcome

Title	Tmax
Description	The time of maximum observed plasma concentration (Tmax)
Time Frame	Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ceftobiprole PK Population
Arm/Group Description	All subjects who received study drug and had adequate samples for determination of time-plasma concentration profiles of ceftobiprole.
Measure Participants	13
Median (Full Range) [hours]	4.00

3. Primary Outcome

Title	AUC0-last
Description	The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-last)
Time Frame	Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ceftobiprole PK Population
Arm/Group Description	All subjects who received study drug and had adequate samples for determination of time-plasma concentration profiles of ceftobiprole.
Measure Participants	13
Median (Full Range) [μg•hours/mL]	60.6

4. Primary Outcome

Title	T>MIC of 4 mg/L
Description	The duration of time after dose for which free-drug concentrations remained above a value of 4 mg/L (T>MIC of 4 mg/L)
Time Frame	Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ceftobiprole PK Population
Arm/Group Description	All subjects who received study drug and had adequate samples for determination of time-plasma concentration profiles of ceftobiprole.
Measure Participants	13
Median (Full Range) [hours]	5.40

Adverse Events

Time Frame	After start of study drug administration through the follow-up visit at study Day 7±3, relevant worsening of a subject's status was to be recorded as an adverse event (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 ITT/Safety Population
Arm/Group Description	All subjects who received any quantity of study drug.
All Cause Mortality
	Ceftobiprole ITT/Safety Population
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Ceftobiprole ITT/Safety Population
	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)
Gastrointestinal disorders
Diaphragmatic hernia	1/15 (6.7%)	1
Nervous system disorders
Cerebral infarction	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Ceftobiprole ITT/Safety Population
	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)
Psychiatric disorders
Drug Dependence	1/15 (6.7%)	1
Skin and subcutaneous tissue disorders
Dermatitis diaper	2/15 (13.3%)	2
Erythema	1/15 (6.7%)	1

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.