Evaluation of Immediate Release Tablet

F901318 - A Two Part Study Designed to Evaluate the Single and Multiple Dose Pharmacokinetics of an Immediate Release Tablet Formulation of F901318

Single dose comparison of liquid and solid formulation, followed by study of effect of high fat breakfast.

Evaluation of multiple dose pharmacokinetics and tolerability

Study Overview

• Status: Completed
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Drug: F901318 SDD; Drug: F901318 IR; Drug: F901318 IR Fasting; Drug: F901318 IR Fed

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom
    • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects will be healthy males or females of any ethnic origin between 18 and 55 years of age and weighing between 50-100 kg (body mass index of 18.0-32.0 kg/m2 inclusive).
2. Females of child bearing potential must be established on a reliable form of contraception and have a negative pregnancy test at screening.
3. 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).
4. Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions.

Exclusion Criteria:

1. Subjects who do not have suitable veins for multiple vene-punctures/cannulation as assessed by the investigator at screening
2. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
3. Male or female subjects who are not willing to use appropriate contraception during the study and until 3 months after the last dose.
4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: F901318 SDD; Liquid formulation	Drug: F901318 SDD; Pharmacokinetics area under curve
EXPERIMENTAL: F901318 IR; Solid formulation	Drug: F901318 IR; Pharmacokinetics area under curve
EXPERIMENTAL: F901318 IR Fasting; Fasting solid formulation	Drug: F901318 IR Fasting; Pharmacokinetics area under curve
EXPERIMENTAL: F901318 IR Fed; Fed solid formulation	Drug: F901318 IR Fed; Pharmacokinetics area under curve

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Area Under Concentration Time Curve	120 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment emergent adverse events	Incidence of Treatment-Emergent Adverse Events [Safety]).	120 hours

Collaborators and Investigators

• Sponsor: F2G Biotech GmbH
• Collaborators: Quotient Clinical

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (ACTUAL): November 1, 2016
• Study Completion (ACTUAL): November 1, 2016

Study Registration Dates

• First Submitted: June 11, 2016
• First Submitted That Met QC Criteria: June 17, 2016
• First Posted (ESTIMATE): June 22, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): November 28, 2016
• Last Update Submitted That Met QC Criteria: November 25, 2016
• Last Verified: June 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: F901318-01-07-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO