Invasive fungal disease in patients with acute myeloid leukemia under chemotherapy MedDRA version: 19.1 Level: PT Classification code 10017533 Term: Fungal infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: F901318
Pharmaceutical Form: Tablet
INN or Proposed INN: F901318
Other descriptive name: F901318
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
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. Patients with body weight =60 kg 7. Group F only: patient receives according to local clinical standard either • no fungal prophylaxis or • only topical fungal prophylaxis (e.g. Ampho moronal®) or • fluconazole as routine fungal prophylaxis 8. Group P only: patient receives posaconazole as fungal prophylaxis according to local clinical standard 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Documented lung infiltrate at screening. 2. Evidence for active fungal infection, such as documented serum GMI =0.5 at screening (within 5 days before study start) 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 (except for patients in group P receiving posaconazole as fungal prophylaxis; see also inclusion criterion 8). Echinocandins and topical polyenes or nystatin are acceptable. 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. 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 ot
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess the safety and tolerability of F901318 tablets in AML patients (all groups). - To determine the pharmacokinetic profile of F901318 tablets in AML patients (all groups). - To assess pharmacokinetic variability of F901318 in AML patients during and after concomitant Fluconazole treatment (Groups F1 and F2). - To assess bioavailability of F901318 in AML patients with concomitant Posaconazole treatment (Group P).;Secondary Objective: - To provide preliminary information on efficacy of F901318 in prevention of invasive Aspergillus infection for Groups F1 and F2. - To develop and evaluate pharmacokinetic models (Nonlinear Mixed Effect Model analysis (NONMEM), simulation) and to characterize population PK - Establish dose adaptation recommendations in the presence of Cytochrome P450 inhibitors - Describe any potential effect of F901318 on Posaconazole & Fluconazole drug levels;Primary end point(s): - Safety and tolerability as assessed by adverse events, physical examination, vital signs, ECGs, and laboratory assessments. - Concentrations of F901318 in plasma; concentration-time profile of F901318 following intake - 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 - Assessment of F901318 plasma concentrations during concomitant Fluconazole treatment and after discontinuation of Fluconazole - Assessment of F901318 plasma concentrations during concomitant Posaconazole treatment ;Timepoint(s) of evaluation of this end point: -AEs will be assessed on every treatment day and at the follow-up (10 days after end of F901318 treatment) and late follow-up (28 days after end of F901318 treatment) visit. -F901318 plasma peak concentration after F901318 intake will be assessed on the second day of F901318 treatment and EOT. F901318 trough level assessments will be done on the first 3 days of F901318 treatment, on day 5, 7, 10, 13 and 16 of F901318 treatment, at EOT and FU. From | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Absence of breakthrough infections. Incidence of invasive fungal disease will be categorized according to EORTC/MSG 2008 criteria into possible/probable/proven IFD by a central end point committee, based on serum galactonannan index and results of bronchoalveolar lavage (BAL, if clinically indicated) and CT (if clinically indicated). - Estimates of model parameters and their precision, goodness-of-fit, individual and mean predictions. - Plasma concentrations of F901318 during concomitant Posaconazole or Fluconazole treatment and after discontinuation of Fluconazole. - Concentration of Fluconazole and Posaconazole in plasma during F901318 treatment.;Timepoint(s) of evaluation of this end point: - Efficacy data will be collected at the last day of study drug treatment and at the follow-up (10 days after end of F901318 treatment) and late follow-up visit (28 days after end of F901318 treatment) -F901318 plasma peak concentration after F901318 intake will be assessed on the second day of F901318 treatment and EOT. F901318 trough level assessments will be done on the first 3 days of F901318 treatment, on day 5, 7, 10, 13 and 16 of F901318 treatment, at EOT and FU. From the measured plasma concentrations the PK parameter will be derived. - Fluconazole and Posaconazole concentrations will be assessed together with F901318 trough levels on the first 3 days of F901318 treatment, on day 5, 7, 10, 13 and 16 of F901318 treatment, at EOT and FU. | — |
Countries
Germany
Contacts
Public ContactProjectmanagement
CTC Cologne
Outcome results
None listed