Infasive fungal disease in patients with acute myeloid leukemia under chemotherapy MedDRA version: 19.0 Level: PT Classification code 10017533 Term: Fungal infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: F901318
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: F901318
Other descriptive name: F901318
Concentration unit: mg/ml milligram(s)/millilitre
Concentr
Sponsors
F2G Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients diagnosed with AML and entering treatment of chemotherapy. 2. Patients are expected to be neutropenic ( 10 days. 3. Provision of written informed consent prior to any study specific procedures. 4. Ability and willingness to comply with the protocol. 5. Patients aged over 18 years. 6. Patient has or will receive within 2 days a multi-lumen central venous catheter as standard of care. 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 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Documented lung infiltrate at screening. 2. Documented serum GMI =0.5 at screening 3. Current IFD or prior history of IFD or patients who received systemic antifungal therapy for proven or probable IFD in the last 12 months. 4. Patients who received any systemic antifungal therapy for more than 72 hours immediately prior to first administration of study medication. Echinocandins and topical polyenes or nystatin are acceptable. Posaconazole and other azoles have to be discontinued at least 3 days before start of F901318. 5. Concomitant exposure to phenobarbital and long acting barbiturates, triazolam, carbamazepine, phenytoin, pimozide, cisaprid, efavirenz, ritonavir, rifabutin, rifampicin, ergot alkaloids (ergotamine, dihydroergotamin), ibrutinib, idelalisib, vinca alkaloids, digoxin, dofetilide, quinidine, St. John´s wort, everolimus, sirolimus, astemizole, terfenadine, methadone, alfentanil, fentanyl and other structurally related opiates, warfarin (see also section 8.8 for details). 6. Documented prolongation of the QTc interval (>450 ms).* 7. Concomitant medication that prolongs QT interval (except for cytostatic drugs used during chemotherapy, such as mitoxantrone). 8. Any other concomitant medical condition that, in the opinion of the investigator, may be an unacceptable additional risk to the patient should he/she participate in the study. 9. History of convulsion. 10. Female patients only: Positive result of pregnancy test or breastfeeding. 11. Female patients of childbearing potential who do not practice sexual abstinence as their common way of life and confirm to stay sexually abstinent also during their participation in the study or who do not use or do not agree to use appropriate contraceptive methods (prior to and during the study, including 14 days after the last dose of study therapy) as defined in ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals (EMA/CPMP/ICH/286/1995). Hormonal contraception alone is not considered appropriate. See section 9.3.2 for additional information. 12. Known hypersensitivity to any component of the study medication. 13. A history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalaemia, cardiomyopathy, sinus bradycardia, symptomatic arrhythmias, family history of long QT Syndrome). 14. Patient has had acute hepatitis in the prior 6 months, chronic hepatitis, cirrhosis (any Child-Pugh class), acute hepatic failure, or acute decompensation of chronic hepatic failure 15. Presence of hepatic disease as indicated by aspartate aminotransferase (AST) or alanine transaminase (ALT)>3 × upper limit of normal (ULN) at Screening. Patients with AST and/or ALT >3 × ULN and 3 × ULN, unless isolated hyperbilirubinemia is directly related to an acute infection or due to known Gilbert’s disease.** 17. Calculated creatinine clearance (CrCl) < 50 mL/minute.** 18. Medical history of oliguria (< 20 mL/h) unresponsive to fluid challenge. 19. Suspected other or additional cause for neutropenia or im
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the pharmacokinetic profile of F901318 intravenous infusion in AML patients at risk for invasive fungal disease during neutropenia (NP). To assess the safety and tolerability of F901318 intravenous infusion and oral formulation dosing regimens in AML patients at risk for invasive fungal disease during neutropenia (NP).;Secondary Objective: -To determine the pharmacokinetic parameters of oral F901318 in AML patients at the last day of F901318 administration. -To provide preliminary information on efficacy of F901318 in prevention of invasive aspergillus infection. Explorative Objective: -To develop and evaluate pharmacokinetic models (Nonlinear Mixed Effect Model analysis (NONMEM), simulation) and to characterize population PK ;Primary end point(s): - Concentrations of F901318 in plasma; concentration-time profile of F901318 following i.v. and oral administration - The derived PK parameters Ctrough, Cmin_ss, Cmax_ss, Cav_ss, AUCT,ss, AUC(0-T), AUC0-t, AUC(0-t_last), t1/2, lambda z, Vss, and CL - Safety and tolerability as assessed by adverse events, physical examination, vital signs, ECGs, and laboratory assessments. ;Timepoint(s) of evaluation of this end point: F901318 plasma concentration after F901318 i.v. treatment will be assessed on every treatment day. From these concentrations the PK parameters will be derived. AEs will be assessed on every treatment day and at the follow-up (14 days after end of F901318 treatment) and late follow-up (35 days after end of F901318 treatment) visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Assessment of Cav_ss and trough level concentrations of F901318 after oral application. - Absence of breakthrough infections. Incidence of invasive fungal disease (IFD) will be categorized according to EORTC/MSG 2008 criteria (De Pauw, Walsh et al. 2008)) into possible/probable/proven IFD by a central end point committee, based on serum galactomannan index and results of bronchoalveolar lavage (BAL) (if clinically indicated). - Estimates of model parameters and their precision, goodness-of-fit, individual and mean predictions.;Timepoint(s) of evaluation of this end point: F901318 plasma concentration after F901318 i.v. treatment will be assessed on every treatment day. From these concentrations the PK parameters will be derived. F901318 plasma concentration after F901318 oral treatment will be assessed on the day of oral treatment Efficacy data will be collected at the last day of study druf treatment, at the follow-up (14 days after end of F901318 treatment) and late follow-up (35 days after end of F901318 treatment) visit. | — |
Countries
Germany
Contacts
Public ContactCTC Cologne - Projectmanagement
CTC Cologne
Outcome results
None listed