Drug-drug Interaction (DDI) Study to Assess Effect of Itraconazole and Rifampicin Upon Olorofim

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1, single-centre, fixed-sequence, open label, drug-drug interaction study in 2 groups of healthy subjects. Group A: to evaluate the effects of itraconazole, a strong inhibitor of cytochrome P450 3A (CYP3A), upon the pharmacokinetics of olorofim . Group B: t o evaluate the effects rifampicin, a strong inducer of CYP3A, upon the pharmacokinetics of olorofim .

Official Title
-----------------
A Phase I, Open Label Study in Healthy Subjects to Evaluate the Effect of Itraconazole and Rifampicin Upon the Pharmacokinetics of a Single Oral Dose of Olorofim.

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Itraconazole oral solution
* Drug: Rifampicin Oral Capsule
* Drug: Olorofim


Participation Criteria
=================
Eligibility Criteria
-----------------
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 32 kg/m2. subjects in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations Exclusion Criteria: Female subjects of child-bearing potential. 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
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort A<br>Itraconazole DDI | Drug: Itraconazole oral solution<br>* 200 mg once daily on Days 6 to 15<br>Drug: Olorofim<br>* Single oral dose on Days 1 and 11<br>* Other names: F901318;|
| Other: Cohort B<br>Rifampicin DDI | Drug: Rifampicin Oral Capsule<br>* 600 mg once daily on Days 6 to 15<br>Drug: Olorofim<br>* Single oral dose on Days 1 and 11<br>* Other names: F901318;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum plasma concentration (Cmax) for olorofim. |  | 16 days | 
| Area under the concentration-time curve to time of last quantifiable concentration (AUC0-tlast) for olorofim. |  | 16 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Cmax (Tmax) of olorofim |  | 16 days | 
| area under the concentration-time curve to infinity (AUC0-∞) for olorofim |  | 16 days | 
| terminal elimination half-life (t½) for olorofim |  | 16 days | 
| Number of subjects with treatment-related adverse events |  | 23 days |