Study of Potential for Interaction of Fluconazole With F901318

NCT02730442 | Completed Phase 1

• 1 other identifier: F01318-01-05-15
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This will be an open label study in two parts. In the first part, F901318 (dose 2 mg/kg IV over 4 hours, Day 1) will be followed by F901318 (2 mg/kg IV over 4 hours) given on Day 8, after dosing with fluconazole 800 mg daily for 1 day (Day 4) and 400 mg daily orally for 4 days (Days 5 to 8). Up to twenty subjects will be included in two cohorts which will undergo the same dosing schedules of fluconazole and F901318 and undergo the same procedures. The first cohort will consist of 12 subjects studied in two groups of six subjects each. If there is clearly a difference in F901318 kinetics detectable before and after dosing with fluconazole in this first cohort, the second cohort will not be studied. If there is no clear difference, the second cohort will also be studied to give a final result. In this cohort, based on the pharmacokinetic findings in cohort 1, the dose of F901318 may be increased to up to 4 mg/kg to establish a dose suitable for phase 2 evaluation. PK sampling for plasma F901318 will continue from before the first dose up to and including 72 hours after dosing. PK sampling for fluconazole will continue from before the first dose and up to 72 hours after the fifth dose. A follow up visit will be conducted 7 +/- 2 days after discharge from the clinical unit following completion of blood sampling following the second dose of F901318 and the fifth dose of fluconazole. The second part of the study will take place if no appreciable change in the pharmacokinetics of either F901318 or fluconazole has been observed in either the first or the second cohorts in the first part of the study. This second part will enrol 12 subjects. These subjects will receive fluconazole 800 mg daily for one day (Day 1) and 400 mg daily orally for 4 days (Days 2 to 5) in combination with F901318 which will be given in a dose of up to 4 mg/kg IV bid for one day (Day 1) followed by 7 doses of intravenous F901318 up to 2.5 mg/kg bid (Days 2 to 5). Pharmacokinetic profiles of F901318 and fluconazole will be obtained during dosing and over a 72-hour period following the final dose of both compounds.

Conditions

Invasive Aspergillosis

Outcome Measures

Primary Outcomes (1)

• Treatment emergent adverse events

  Adverse events

  5 days

Secondary Outcomes (1)

• Pharmacokinetics area under concentration/time curve 0-t

  5 days

Study Arms (1)

Single dose F901318 with fluconazole

EXPERIMENTAL

AUC0-t for F901318 will be assessed before and after 5 days of treatment with fluconazole oral

Drug: F901318; Drug: Fluconazole

Interventions

F901318 DRUG

Administration of F901318 intravenously

Also known as: Antifungal agent

Single dose F901318 with fluconazole

Fluconazole DRUG

Oral administration

Also known as: Antifungal agent

Single dose F901318 with fluconazole

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects will be males and females of any ethnic origin aged between 18 and 45 years of age and weighing 50-100 kg inclusive.
• Subjects must be in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations (congenital non haemolytic hyperbilirubinaemia is acceptable).
• Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions.

You may not qualify if:

• Male and female subjects who are not willing to use appropriate contraception during the study and for three months thereafter.
• Subjects who have received any prescribed systemic or topical medication within 14 days of the dose administration unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
• Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the dose administration (with the exception of vitamin/mineral supplements and paracetamol) unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
• Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of the dose administration unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety. For at least 2 weeks prior to dosing and until all blood samples and observations are completed on Day 18 +/- 2 (Part 1) or Day 15 +/- 2 (Part 2), subjects will not be allowed to eat any food or drink any beverage containing alcohol, grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family e.g. kale, broccoli, watercress, spring greens, kohlrabi, Brussels sprouts, mustard and charbroiled meats.

Sponsors & Collaborators

• F2G Biotech GmbH: lead
• Celerion Ltd: collaborator

Study Sites (1)

CELERION

Belfast, Northern Ireland, BT9 6AD, United Kingdom

Location

MeSH Terms

Interventions

olorofim; Antifungal Agents; Fluconazole

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• A Stewart

  Celerion Ltd

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 1, 2016
• First Posted: April 6, 2016
• Study Start: February 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: February 2, 2017

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)