A Biopharmaceutics Study to Assess the Pharmacokinetics of Single Oral and IV Doses of Olorofim

Study Overview
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Brief Summary
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This is a Phase I, single-centre, randomised, open-label, crossover study in 24 healthy subjects. Twelve subjects will each receive olorofim as a single IV infusion, single oral dose (fasted) and single oral dose (fed) and 12 subjects will each receive olorofim orally as intact tablets and via NG tube

Official Title
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A Phase I, Open-label, Randomised Biopharmaceutics Study in Healthy Subjects to Evaluate the Pharmacokinetics, Safety and Tolerability of Single Doses of IV and Oral Formulations of Olorofim

Conditions
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Healthy

Intervention / Treatment
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* Drug: Olorofim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males or females of any ethnic origin between 18 and 55 years of age subjects weighing between 50 and 100 kg, with a body mass index (BMI) between 18 and 30 kg/m2. subjects in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations Exclusion Criteria: Male subjects (or their partners) who are not willing to use appropriate contraception during the study and for 3 months after end of dosing. Female subjects who are pregnant or lactating. Subjects who have received any prescribed systemic or topical medication within 14 days of first dose administration Subjects who have used any non-prescribed systemic or topical medication within 7 days of first dose administration Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of first dose administration Subjects with or history of clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatry, respiratory, metabolic, endocrine, ocular haematological or other major disorders as determined by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 3 Treatment Periods for Cohorts A and B 2 Treatment Periods for Cohort C
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: IV<br>2 h IV infusion (Groups A/B) | Drug: Olorofim<br>* 150 mg<br>* Other names: F901318;|
| Other: oral (fasted)<br>30 mg tablets given after an overnight fast (Groups A/B) | Drug: Olorofim<br>* 150 mg<br>* Other names: F901318;|
| Other: oral (fed)<br>30 mg tablets given after a high fat breakfast (Groups A/B) | Drug: Olorofim<br>* 150 mg<br>* Other names: F901318;|
| Other: oral (intact tablet)<br>30 mg tablets (Group C) | Drug: Olorofim<br>* 150 mg<br>* Other names: F901318;|
| Other: oral (NG tube)<br>30 mg tablets in water via NG tube (Group C) | Drug: Olorofim<br>* 150 mg<br>* Other names: F901318;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum plasma concentration (Cmax) for olorofim |  | 35 days | 
| area under the concentration time curve to time of last quantifiable concentration (AUC0-tlast) for olorofim |  | 35 days | 
| Absolute bioavailability of olorofim (F) |  | 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Cmax (TMax) for olorofim |  | 35 days | 
| area under the concentration time curve to infinity (AUC0-∞) for olorofim |  | 35 days | 
| terminal elimination half-life (t½) for olorofim |  | 35 days | 
| Number of subjects with treatment-related adverse events |  | 35 days |