E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Infection ou inflammation méningée |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027199 |
E.1.2 | Term | Meningitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize the PK of ceftobiprole after one intravenous infusion of ceftobiprole medocaril in patients with indwelling external CSF shunts who had suspected or documented meningitis or ventriculitis and to characterize the PK of ceftobiprole in the cerebrospinal fluid. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of a single intravenous infusion of ceftobiprole medocaril (one 500 mg 2h-infusion) in patients with indwelling external CSF shunts. To characterize the PK of Ceftobiprole after a single intravenous infusion over 2 hours. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients (> 18 years) o Provision of informed consent prior to any study specific procedures o Female patients of childbearing potential may be entered if pregnancy testing is negative and the patient agrees to abstain from procreational sexual intercourse or must use double-barrier contraceptive measures for the duration of the study - Presence of an indwelling external CSF access device (ventriculostomy or lumbar drain) - Presence of inflamed meninges as a result of documented or suspected meningitis or ventriculitis. Patients with both clinical symptoms (fever, headache, meningismus, and altered mentation) and laboratory parameters (CSF leukocytosis, defined as a CSF white blood cell count [WBC] of >103, elevated CSF protein, defined as CSF protein of >1g/l, reduced CSF glucose, defined as CSF glucose of <0.3g/l, or a positive CSF Gram stain or culture) indicative of CNS infection were deemed to have definitive bacterial meningitis/ventriculitis. Inflamed meninges were defined as the presence of >5 leukocytes/mm3 of CSF. |
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E.4 | Principal exclusion criteria |
- Hypersensitivity to MABELIO® (ceftobiprole) or to one of its excipient or another 3rd cephalosporin - Hypersensitivity to cephalosporin - Imeediate or severe hypersensitivity to β-lactam antimicrovial - Pregnant or breast feeding women - Renal insufficiency defined as creatinine clearance < 50 mL/min - Patient with creatinine clearance > 150 mL/min - patients with conditions known or suspected to alter pharmacokinetics (i.e., burn or cystic fibrosis patients) - refusal to participate - person not affiliated to the social security - person with antibacterial treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mesure de la concentration dans le sang et dans le LCR de la ceftobiprole |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Evaluation de la tolérance et de la sécurité. La tolérance et la sécurité de la perfusion (500 mg sur 2 heures) de ceftobiprole seront évaluées sur les reports des évènements indésirables, les signes vitaux, électrocardiogrammes, résultats biologiques, et les résultats des examens physiques. Ces évaluations seront faites en prenant en compte les comorbidités et maladies des patients. Les évaluations auront lieu avant l’administration de la drogue, immédiatement après la perfusion de la ceftobiprole et à J3. Les participants à l’étude seront suivis tout au long de la perfusion et les jours suivants pour déceler d’éventuels effets indésirables. Les relations entre évènements indésirables et produit expérimental seront évaluées par un médecin qualifié et seront en général basées sur des considérations telles que la relation temporelle avec l'administration du produit expérimental, les antécédents médicaux pertinents du sujet, et si l’évènement peut être lié à un état préexistant. Une attention toute particulière sera prêtée aux effets indésirables les plus fréquemment observés.
Pharmacocinétique: la pharmacocinétique de la ceftobiprole sera établie par des mesures de sa concentration aux temps 0h, 0.5h, 1h, 3h, 6h, 12h et 24h |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Avant injection et jusqu'à 3 jours après l'injection |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |