Clinical Trial Results:
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
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Summary
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EudraCT number |
2013-004614-18 |
Trial protocol |
BE DE LT PL LV Outside EU/EEA |
Global end of trial date |
07 Jul 2020
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Results information
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Results version number |
v2(current) |
This version publication date |
01 Jun 2023
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First version publication date |
27 Dec 2020
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BPR-PIP-001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02527681 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Basilea Pharmaceutica International Ltd.
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Sponsor organisation address |
Grenzacherstrasse 487, Basel, Switzerland, 4058
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Public contact |
Chief Medical Officer, Marc Engelhardt, Basilea Pharmaceutica International Ltd., +41 797010551, marc.engelhardt@basilea.com
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Scientific contact |
Chief Medical Officer, Marc Engelhardt, Basilea Pharmaceutica International Ltd., +41 797010551, marc.engelhardt@basilea.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000205-PIP02-11 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Sep 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Jul 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Jul 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective was to characterise the pharmacokinetics of a single dose of ceftobiprole in neonates and infants aged ≤ 3 months.
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Protection of trial subjects |
As eligible subjects were already receiving standard-of-care intravenous antibiotic treatment, the administration of ceftobiprole did not impose substantial additional discomfort or risk. Laboratory tests required for screening, but which had been performed within the 48 hours prior to ceftobiprole dosing, were not to be repeated, regardless of whether they had been performed before or after signing of the ICF.
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Background therapy |
Standard-of-care antibiotic | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
22 Nov 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 2
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Country: Number of subjects enrolled |
Poland: 2
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Country: Number of subjects enrolled |
Germany: 3
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Country: Number of subjects enrolled |
Latvia: 1
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Country: Number of subjects enrolled |
Lithuania: 2
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Country: Number of subjects enrolled |
United States: 5
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Worldwide total number of subjects |
15
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
9
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Infants and toddlers (28 days-23 months) |
6
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment started on 22-Nov-2016 and ended on 18-Feb-2020. 45 neonate or infant subjects, stratified for gestational and postnatal age, were planned to be enrolled in three sequential cohorts. After agreement with the EMA Paediatric Committee, the study was terminated after enrolment of the full-term cohort. No pre-term subjects were enrolled. | ||||||
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Pre-assignment
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Screening details |
Subjects with documented or presumed bacterial infection receiving standard-of-care antibiotic treatment were screened. | ||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Ceftobiprole ITT/Safety population | ||||||
Arm description |
Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for intravenous administration. Ceftobiprole is characterised by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Ceftobiprole medocaril
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
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.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ceftobiprole ITT/Safety population
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Reporting group description |
Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for intravenous administration. Ceftobiprole is characterised by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens. | ||
Subject analysis set title |
Pharmacokinetics analysis population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The pharmacokinetics analysis population comprised all subjects who received study drug and had adequate samples for determination of time-plasma concentration profiles of ceftobiprole.
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End point title |
Cmax [1] | ||||||||
End point description |
The maximum observed plasma concentration (Cmax)
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End point type |
Primary
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End point timeframe |
Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In line with the Paediatric Investigation Plan (PIP) issued by the EMA Paediatric Committee, descriptive statistics have been agreed and is appropriate for this clinical study endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Tmax [2] | ||||||||
End point description |
The time of maximum observed plasma concentration (Tmax)
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End point type |
Primary
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End point timeframe |
Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In line with the Paediatric Investigation Plan (PIP) issued by the EMA Paediatric Committee, descriptive statistics have been agreed and is appropriate for this clinical study endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
AUC0-last [3] | ||||||||
End point description |
The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-last)
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End point type |
Primary
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End point timeframe |
Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In line with the Paediatric Investigation Plan (PIP) issued by the EMA Paediatric Committee, descriptive statistics have been agreed and is appropriate for this clinical study endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
T>MIC of 4 mg/L [4] | ||||||||
End point 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)
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End point type |
Primary
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End point timeframe |
Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In line with the Paediatric Investigation Plan (PIP) issued by the EMA Paediatric Committee, descriptive statistics have been agreed and is appropriate for this clinical study endpoint |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
After start of study drug administration through the follow-up visit at study Day 7±3, relevant worsening of a patient’s status was to be recorded as an adverse event.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||
Dictionary version |
20.1
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Reporting groups
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Reporting group title |
Ceftobiprole ITT/Safety population
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Reporting group description |
Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for intravenous administration. Ceftobiprole is characterised by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens. | ||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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28 May 2018 |
Administrative change: new pharmacovigilance service provider. |
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21 Mar 2019 |
Reduction in the number of laboratory blood tests at screening and at the follow-up evaluation. Extension of the window from 24 to 48 hours in which laboratory results available as standard of care could be used for screening. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
