An open-label clinical study to evaluate the safety and distribution in the body of a new drug (F901318), to be given as a tablet, to prevent fungal infection in patients undergoing chemotherapy of leukemia

Phase 1

• Conditions: Invasive fungal disease in patients with acute myeloid leukemia under chemotherapy; MedDRA version: 19.1Level: PTClassification code 10017533Term: Fungal infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2016-002271-97-DE
• Lead Sponsor: F2G Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-23
• Last Update Posted: 23 March 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1.Patients diagnosed with AML and entering treatment of chemotherapy.
2.Patients are expected to be neutropenic (< 500 ANC/µl) for > 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

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 <5 × ULN are eligible if these elevations are acute, not accompanied by a total bilirubin =2xULN and documented by the investigator as being directly related to an infectious process being treated. During the clinical study, the investigator is responsible for, without delay, determining whether the patient meets potential Hy’s law criteria (according to FDA [28]).
16.Patient has a total bilirubin >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified