Study on Safety and Pharmacokinetics of Intravenous F901318 for Fungal Prophylaxis in AML Patients

NCT02856178 | Withdrawn Phase 1

• 1 other identifier: F901318C20
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study assesses the pharmacokinetics and safety of the new antifungal F901318 in AML patients.

Conditions

Pulmonary Aspergillosis - Invasive; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Collection of adverse events, results of physical examination, vital signs, ECGs, and laboratory assessments during F901318 intravenous infusion and oral formulation.

  57 days

Secondary Outcomes (14)

• Concentration-time profile of F901318 following i.v. administration

  14 days

• Measured concentration of F901318 at the end of an i.v. dosing interval at steady state (Ctrough)

  14 days

• Minimum observed plasma or serum, concentration of F901318 during an i.v. dosing interval at steady state (Cmin, ss)

  14 days

• Maximum observed plasma or serum, concentration of F901318 during an i.v. dosing interval at steady state (Cmax, ss)

  14 days

• Average plasma or serum concentration of F901318 at steady state after i.v. administration (Cav,ss)

  14 days

Study Arms (1)

F901318 + Caspofungin

EXPERIMENTAL

Patients will receive F901318 intravenously, starting 24 - 72 h after last chemotherapy infusion: * Day 1: 4.0 mg/kg i.v. b.i.d. * Day 2 until resolution of neutropenia (max. until day 14): 2.0 mg/kg i.v. b.i.d. * Day after last i.v. application: 2.0 mg/kg oral q.d. Concomitant medication: For Candida prophylaxis, concomitant caspofungin will be administered from the 4th day of chemotherapy until end of neutropenia: * Chemo day 4: Caspofungin 70 mg i.v. q.d. * Chemo day 5 until resolution of neutropenia or until end of F901318 treatment (day 15): Caspofungin 50 mg i.v. q.d. All patients will undergo chemotherapy for acute leukaemia according to local clinical standard.

Drug: F901318; Drug: Caspofungin

Interventions

F901318 DRUG

F901318 treatment starting after completion of chemotherapy. Max. 14 days of intravenous F901318 b.i.d. treatment, followed by one oral dose of F901318. Loading doses 4 mg/kg b.i.d. , maintenance doses 2 mg/kg b.i.d.

F901318 + Caspofungin

Caspofungin DRUG

Intravenous Caspofungin treatment starting during chemotherapy for concomitant prophylaxis of fungal infection. Loading dose 70 mg q.d., maintenance doses 50 mg q.d.

Also known as: Cancidas®

F901318 + Caspofungin

Eligibility Criteria

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

You may qualify if:

• Patients diagnosed with AML and entering treatment of chemotherapy.
• Patients are expected to be neutropenic (\< 500 ANC/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.
• Patient has or will receive within 2 days a multi-lumen central venous catheter as standard of care.

You may not qualify if:

• Documented lung infiltrate at screening.
• Documented serum GMI ≥0.5 at screening
• Current IFD or prior history of IFD or patients who received systemic antifungal therapy for proven or probable IFD in the last 12 months.
• 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.
• Concomitant exposure to phenobarbital and long acting barbiturates, triazolam, carbamazepine, phenytoin, pimozide, cisapride, 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.
• 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 agree to not have sexual intercourse during 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.
• 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 \[28\]).

Sponsors & Collaborators

• F2G Biotech GmbH: lead
• University Hospital of Cologne: collaborator

MeSH Terms

Conditions

Invasive Pulmonary Aspergillosis; Leukemia, Myeloid, Acute

Interventions

olorofim; Caspofungin

Condition Hierarchy (Ancestors)

Pulmonary Aspergillosis; Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Echinocandins; Peptides, Cyclic

Study Officials

• Oliver Cornely, PhD, MD

  University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: August 4, 2016
• Study Start: April 20, 2017
• Primary Completion: April 20, 2017
• Study Completion: April 20, 2017
• Last Updated: February 15, 2018

Record last verified: 2016-08