Safety and Pharmacokinetics of Oral F901318 (Fluconazole and Posaconazole) IN Aml Leukaemia

NCT03036046 | Withdrawn Phase 1

• 1 other identifier: F901318C21
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Non-randomized, multi-centre, open label, uncontrolled, multiple dose, phase IIa study. A total of 18 patients diagnosed with acute myeloid leukaemia (AML) scheduled for chemotherapy and expected to be neutropenic (\<500 Absolute neutrophil count (ANC)/µl) for \>10 days will be treated. F901318 will be given in conjunction with fluconazole or posaconzaole in order to assess safe treatment regimens for both combinations.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Safety (adverse events)

  Adverse events

  63 days

Secondary Outcomes (1)

• Pharmacokinetics (Area under concentration/time curve)

  14 days

Study Arms (3)

F901318 with fluconazole low dose

EXPERIMENTAL

safety assessment

Drug: F901318 with fluconazole low dose

F901318 with fluconazole high dose

EXPERIMENTAL

safety assessment

Drug: F901318 with fluconazole high dose

F901318 with posaconazole

EXPERIMENTAL

safety assessment

Drug: F901318 with posaconazole

Interventions

F901318 with fluconazole low dose DRUG

adverse events

F901318 with fluconazole low dose

F901318 with fluconazole high dose DRUG

adverse events

F901318 with fluconazole high dose

F901318 with posaconazole DRUG

adverse events

F901318 with posaconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participating patients need to fulfil all of the following criteria:
• Patients diagnosed with AML and entering treatment of chemotherapy.
• Patients are expected to be neutropenic (ANC \<500/µl) for \>10 days.
• Provision of written informed consent prior to any study specific procedures.
• Ability and willingness to comply with the protocol.
• Patients aged over 18 years.
• Patients with body weight ≥60 kg
• 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
• Group P only: patient receives posaconazole as fungal prophylaxis according to local clinical standard

You may not qualify if:

• Any of the following will exclude a patient from the study:
• Documented lung infiltrate at screening.
• Evidence for active fungal infection, such as documented serum GMI ≥0.5 at screening (within 5 days before study start)
• Current IFD or prior history of IFD or patients who received systemic antifungal therapy for proven or probable IFD in the last 12 months.
• 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).
• Documented prolongation of the QTc interval (\>450 ms).
• Concomitant medication that prolongs QT interval (except for cytostatic drugs used during chemotherapy, such as mitoxantrone).
• 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.
• History of convulsion.
• Female patients only: Positive result of pregnancy test or breastfeeding.
• 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.
• Known hypersensitivity to any component of the study medication.
• 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).
• 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
• 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 \[16\]).

Sponsors & Collaborators

• F2G Biotech GmbH: lead
• The Clinical Trials Centre Cologne: collaborator
• Klinik für Hämatologie, Aachen: collaborator
• Medizinische Klinik Würzburg: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

olorofim; Fluconazole; posaconazole

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Oliver A Cornely, MD

  University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients in group low dose fluconazole will be enrolled ahead of group high dose fluconazole. Group posaconazole will be enrolled in parallel according to prevaling practice in the institutions involved in the study

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 30, 2017
• Study Start: March 1, 2017
• Primary Completion: September 1, 2017
• Study Completion: March 1, 2018
• Last Updated: February 15, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share