Evaluation of Immediate Release Tablet
Condition: Invasive Aspergillosis
MeSH terms: Aspergillosis
Study type: Interventional
Phase: Phase 1

Summary: 
      Single dose comparison of liquid and solid formulation, followed by study of effect of high
      fat breakfast.

      Evaluation of multiple dose pharmacokinetics and tolerability
    

Detailed description: 
      The study will be split into 2 parts, Part 1, ( A and B), and Part 2.

      Part 1A Part 1A of the study will be a single centre, open label, 2-way crossover in healthy
      male and female volunteers and will assess the relative bioavailability of a single 360 mg
      dose (as 3 x 120mg tablets) of F901318 IR tablet formulation in comparison to a 360 mg dose
      of an SDD suspension for oral dosing. It is planned that 10 volunteers will be enrolled to
      Part 1A of the study. These 10 subjects will continue into Part 1B of the study.

      There will be a minimum washout of 10 days between doses provided to volunteers.

      Following Part 1A there will be a two week period of interim analysis during which safety and
      pharmacokinetic data will be reviewed. In order to assess doses within the therapeutic range
      in Part 1B, a decision will be made using the available data, on whether the dose of F901318
      IR tablet formulation should be altered. Dose will be altered by amending the number of units
      dosed.

      Part 1B Following the dose decision meeting where data obtained in Part 1A of the study is
      reviewed, the selected dose of F901318 IR tablet formulation will be assessed in a further
      single centre, open label, 2-way crossover in healthy male and female volunteers. The
      selected dose will be administered in the fed (30 minutes following an FDA high fat meal) and
      fasted states in a randomised fashion. .

      There will be a minimum washout of 10 days between doses provided to volunteers.

      Following Part 1B there will period a period of interim analysis during which safety and
      pharmacokinetic data will be reviewed. In order to assess doses within the therapeutic range
      in Part 2, a decision will be made using the available data, on the dose of F901318 IR
      formulation to be dosed in Part 2. Dose will be altered by amending the number of units
      dosed. It will also be determined if doses in Part 2 will be administered in the fed or
      fasted state.

      Part 2 In part 2, the dose(s) anticipated to yield therapeutic plasma concentrations will be
      tested over a 10-day period. This will be a double blind placebo controlled, randomised,
      parallel group design in 10 healthy male and female subjects, 8 taking active compound and 2
      taking placebo. In order to mimic the expected treatment schedule in phase 2 trials, it is
      anticipated that there will be a loading dose given over 1 or 2 days, followed by once daily
      or twice daily doses of study drug up to a total of 10 days.

      In both parts of the study, blood will be drawn for safety and pharmacokinetic evaluation.
      Adverse events, vital signs and 12 lead ECGs will be monitored throughout. In Part 1, Holter
      monitoring will be performed for 12 hours after each dose. Part 2, ECG Holter monitoring will
      be performed on Days 1 and 10 only.
    

Intervention name(s): F901318 SDD; F901318 IR; F901318 IR Fasting; F901318 IR Fed
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Pharmacokinetics area under curve; Pharmacokinetics area under curve; Pharmacokinetics area under curve; Pharmacokinetics area under curve
Intervention MeSH terms: Olorofim
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment