F901318 Multiple Ascending Dose Study

F901318 - A Phase I, Double-Blind, Placebo Controlled, Single and Multiple Ascending Intravenous Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Male Subjects

Double blind, placebo controlled, parallel group ascending dose study evaluating single and multiple (x8 days) dose levels of F901318 in groups of male healthy subjects with the objective of defining a dosing schedule for phase ll clinical trials. F901318, a novel and potent antifungal agent for the treatment of invasive aspergillosis, will be delivered intravenously in a range of dosing schedules driven by pharmacokinetic evaluation in real time. Safety and tolerability of those schedules will also be assessed.

Study Overview

• Status: Completed
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Drug: Placebo; Drug: F901318

Detailed Description

Double blind, placebo controlled, ascending single and multiple intravenous dose, sequential group study. This will be a study in two parts. In the first part, up to twenty four subjects will complete the study in up to 3 cohorts (Groups A to C), each group consisting of 8 subjects, six of whom will receive active compound and two will receive placebo for eight days. Each subject will be on study for approximately 7 weeks. Each subject will participate in one treatment cohort only, residing at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 13 (120 hours post the last dose).

This first part (Part 1) will test doses already evaluated in the previous single ascending dose study (F901318-01-01-14, 0.25-4 mg/kg given over 4 hours). The dose levels for the study are expected to be 1.5, 3 and 4 mg/kg/day given as a four hour infusion once daily.

In the second part of the study (Part 2), doses higher than those previously evaluated may be studied and/or different dosing schedules designed to deliver a maximum tolerated dose over 24 hours. If a dose level higher than those previously studied is chosen, there will be an optional single dose studied initially for safety and pharmacokinetic profile (Part 2A), followed about 14 days later in another group of subjects by exposure at that same dose level over 8 consecutive days (Part 2B). These higher doses may be given in a once or twice daily dosing schedule. Six subjects will receive active compound and two will receive placebo in both the single dose and multiple dose cohorts. The single dose cohorts will receive study drug in a sentinel group design in which two subjects receive study drug (one active and one placebo) on the first day and the rest of the group one day later. There will be a review of safety data by the Principal Investigator and the Medical Monitor after the first two subjects have been dosed and before the last six subjects are dosed in each cohort in part 2A.

In Part 2, up to forty-eight subjects will complete the study in up to 6 cohorts (Part 2A, Groups D1 to F1, single day dosing, and Part 2B, Groups D2 to F2 eight days' dosing). Subjects in Parts 1 and 2B will be on the study for approximately 7 weeks and Part 2A for approximately 8 weeks. Each subject will participate in one treatment cohort only, residing at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 6 (120 hours after the single dose in Parts 1 and 2A) and from Day -1 (the day before dosing) to Day 13 (120 hours after the first dose in Part 2B). The proposed total daily dose levels for Part 2 will be up to 10 mg/kg/day given either once daily or in two split daily doses. The duration of the infusions will be between 2 and 24 hours which may include a loading dose to achieve therapeutic plasma concentrations as quickly as possible.

All subjects will return for a post-study visit 8 to 10 days after the last dose of study medication.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • London, UK, United Kingdom, NW10 7EW
      • Hammersmith Medicines Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Subjects will be males of any ethnic origin between 18 and 45 years of age and weighing 60-100 kg inclusive
2. 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)
3. Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions
4. Subjects must have ophthalmology assessments within the normal limits at screening. This includes normal Meibomian gland function

Exclusion Criteria:

1. Male subjects who are not willing to use appropriate contraception (such as a condom) during the study and until follow up
2. Subjects who have received any prescribed systemic or topical medication within 14 days of dosing with study drug unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety
3. Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of dosing with study drug (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
4. Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of dosing with study drug unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety
5. Subjects who are still participating in a clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical or biological entity) in the past 3 months since the last dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A active; Six subjects receiving F901318 1.5 mg/kg intravenously for eight days	Drug: F901318; Administration of active compound
Placebo Comparator: A placebo; Two subjects receiving F901318 placebo intravenously for eight days	Drug: Placebo; Administration of placebo
Experimental: B active; Six subjects receiving F901318 3 mg/kg intravenously for eight days	Drug: F901318; Administration of active compound
Placebo Comparator: B placebo; Two subjects receiving F901318 placebo intravenously for eight days	Drug: Placebo; Administration of placebo
Experimental: C active; Six subjects receiving F901318 4 mg/kg intravenously for eight days	Drug: F901318; Administration of active compound
Placebo Comparator: C placebo; Two subjects receiving F901318 placebo intravenously for eight days	Drug: Placebo; Administration of placebo
Experimental: D1 active; Six subjects dosed for one day with F901318 intravenously dose to be determined	Drug: F901318; Administration of active compound
Placebo Comparator: D1 placebo; Two subjects receiving F901318 placebo intravenously for one day	Drug: Placebo; Administration of placebo
Experimental: E1 active; Six subjects dosed for one day with F901318 intravenously dose to be determined	Drug: F901318; Administration of active compound
Placebo Comparator: E1 placebo; Two subjects receiving F901318 placebo intravenously for one day	Drug: Placebo; Administration of placebo
Experimental: F1 active; Six subjects dosed for one day with F901318 intravenously dose to be determined	Drug: F901318; Administration of active compound
Placebo Comparator: F1 placebo; Two subjects receiving F901318 placebo intravenously for one day	Drug: Placebo; Administration of placebo
Experimental: D2 active; Six subjects dosed for eight days with F901318 intravenously dose to be determined	Drug: F901318; Administration of active compound
Placebo Comparator: D2 placebo; Two subjects receiving F901318 placebo intravenously for eight days	Drug: Placebo; Administration of placebo
Experimental: E2 active; Six subjects dosed for eight days with F901318 intravenously dose to be determined	Drug: F901318; Administration of active compound
Placebo Comparator: E2 placebo; Two subjects receiving F901318 placebo intravenously for eight days	Drug: Placebo; Administration of placebo
Experimental: F2 active; Six subjects dosed for eight days with F901318 intravenously dose to be determined	Drug: F901318; Administration of active compound
Placebo Comparator: F2 placebo; Two subjects receiving F901318 placebo intravenously for eight days	Drug: Placebo; Administration of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety: adverse events	adverse events	13 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacokinetics AUC	area under concentration time curve	13 days
pharmacokinetics Cmin	drug level in blood 24 hours after dosing	13 days

Collaborators and Investigators

• Sponsor: F2G Biotech GmbH
• Collaborators: Hammersmith Medicines Research
• Investigators: Principal Investigator: Frans van den Berg, MB ChB, Hammersmith Medicines Research

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: January 20, 2015
• First Posted (Estimate): January 21, 2015

Study Record Updates

• Last Update Posted (Estimate): September 19, 2016
• Last Update Submitted That Met QC Criteria: September 16, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Aspergillosis; Anti-Infective Agents; Antifungal Agents; Olorofim
• Other Study ID Numbers: F901318-01-02-14