F901318 Multiple Ascending Dose Study
Condition: Invasive Aspergillosis
MeSH terms: Aspergillosis
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): F901318; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Administration of active compound; Administration of placebo
Intervention MeSH terms: Olorofim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment