infections with fosfomycin-susceptible organisms e.g. bacteremia, soft tissue infections, central nervous system infections, endocarditis, abscesses etc. MedDRA version: 20.1 Level: PT Classification code 10060945 Term: Bacterial infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Fosfomycin
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Fosfomycin
CAS Number: 26016-99-9
Current Sponsor code: Fosfo
Other descriptive name: FOSFOM
Sponsors
Department of Clinical Pharmacology, Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: PART A: • Healthy males aged between 18 and 50 years • Body mass index between 18 and 30 • No regular medication within the last 2 weeks prior to the first study day • Written informed consent given by volunteers after being provided detailed information about the nature, risks, and scope of the clinical study as well as the expected desirable and adverse effects of the drug • Willingness to adhere to adequate contraception measures for the entire duration of the study until one month has elapsed from end-of-study visit • No legal incapacity and/or other circumstances rendering the subject unable to understand the nature, scope and possible consequences of the study PART B: • Age above 18 years • Intubated patients admitted to an intensive care unit of the Vienna general hospital (AKH) participating in this study • Sequential organ failure assessment (SOFA) score > 6 at study inclusion • Body mass index (calculated from measured or estimated body weight and height) between 18 and 40 • Indication for treatment with fosfomycin at a total daily dose of 24g (at the discretion of the treating physicians) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: PART A: • Known allergy or hypersensitivity against study drug • History of severe allergic or anaphylactic reactions to any medication • Blood donation within the last 4 weeks prior to study • Participation in another clinical study within the last 4 weeks prior to study • Alcohol or drug abuse • Smoker • Abnormalities in ECG including corrected QT interval, laboratory tests or physical examination that are considered clinically relevant (up to investigators judgement) at screening • History or presence of significant disease state(s) incompatible with study participation in the judgment of the investigators • Sero-positivity for human immunodeficiency virus (HIV) at screening • Sero-positivity for hepatitis B or C virus (HepB antigen, HepC antibody) at screening • Unreliability and/or lack of cooperation • Other objections to participate in the study in the opinion of the investigator PART B: • Known allergy or hypersensitivity against study drug • Any disease considered relevant for proper performance of the study, or risks to the patient, at the discretion of the investigator • Impaired renal function denoted by an estimated GFR of <40 mL/min according to Cockroft-Gault at study inclusion • Requiring hemofiltration or hemodialysis • Pregnancy • Other factors that preclude study participation in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PART A: to determine pharmacokinetics of fosfomycin in plasma of healthy volunteers receving fosfomycin both as intermittent and continuous infusion in a crossover fashion PART B: to determine pharmacokinetics of fosfomycin in plasma and ELF of critically ill patients receiving fosfomycin as continuous infusion;Secondary Objective: PART A: •Analysis of pharmacokinetic/pharmacodynamic (PK/PD) targets considering currently established/discussed breakpoints •Probability of target attainment (PTA) analysis for different pathogens (in collaboration) •Safety and tolerability of both modes of administration PART B: •Analysis of pharmacokinetic/pharmacodynamic (PK/PD) targets and comparison to currently established/discussed breakpoints •Probability of target attainment (PTA) analysis for different pathogens (in collaboration). •Collection of safety data regarding continuously administered fosfomycin. Exploratory: assessment of clinical cure rate and microbiological cure rate ;Primary end point(s): Area under the plasma concentration time curve (AUC) from 0 to 24 hours (AUC0-24) calculated by multiplying AUC0-8 (as determined in part A, study period I) times three and calculated by multiplying steady-state concentrations under continuous infusion times 24 (in part A, study period II as well as in part B);Timepoint(s) of evaluation of this end point: on study days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Maximum concentration (Cmax), time to maximum concentration (tmax), half-life (t1/2), total body clearance (CL), apparent volume of distribution (VD), concentration during therapy and at defined points after end of therapy (Cx) in plasma (PARTs A and B) or ELF (PART B), respectively. -PK/PD relationships: ratio of AUC from 0 to 24 hours to the minimum inhibitory concentration (AUC0-24/MIC); percentage of the dosing interval during which drug concentrations exceed the MIC (%T>MIC); ratio of the peak concentration to the MIC (Cmax/MIC) -probability of target attainment (PTA) analysis for relevant pathogens (collaboration) -collection of adverse events during study participation Exploratory endpoints (PART B only): Clinical cure rate (CCR) and (in case a pathogen that is susceptible to fosfomycin was isolated before initiation of fosfomycin treatment) microbiological cure rate (MCR) will be assessed in an exploratory way. ;Timepoint(s) of evaluation of this end point: on study days | — |
Countries
Austria
Contacts
Public ContactOffice
Department of Clinical Pharmacology
Outcome results
None listed