A Phase I Study to Assess the Pharmacokinetics of Olorofim in Subjects With Hepatic Impairment

Study Overview
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Brief Summary
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A single oral dose study to investigate the PK and safety of olorofim in mild and moderately hepatically impaired subjects compared to subjects with normal hepatic function.

Official Title
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A Phase I, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of Olorofim in Subjects With Hepatic Impairment

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Olorofim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 18 to 70 years of age inclusive, at the time of signing the informed consent. Body weight ≥50 kg and BMI within the range 18 to 35 kg/m2 (inclusive Subjects with mild hepatic impairment will have grade A Child-Pugh score of 5 to 6 at screening and Day -1: Subjects with moderate hepatic impairment: will have grade B Child-Pugh score of 7 to 9 at screening and Day -1 Subjects with normal liver function must be in good health, as determined by a medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluations Subjects with normal liver function are matched by gender, age (±10 years) and BMI (± 20%) to at least one hepatically impaired subject. Exclusion Criteria: Subjects who have an abnormality in the 12-lead ECG that, in the opinion of the Investigator, increases the risk of participating in the study Subjects with any history of convulsion (other than childhood febrile convulsion before the age of 6 years). Subjects who have any clinically significant allergic disease (excluding mild or seasonal allergies such as contact dermatitis or hay fever) as determined by the Investigator. Subjects with a history of or any concomitant active malignancy. Subjects with a history of drug or alcohol abuse. Subjects with, or with a history of, any clinically significant neurological, renal, cardiovascular, psychiatric, respiratory, metabolic, endocrine, ocular (including minor trauma), hematological, or other major disorders as determined by the Investigator. Subjects with signs or symptoms consistent with a COVID-19 infection at screening or Day -1 Hepatically impaired subjects with liver transplantation, autoimmune liver disease, or drug-induced liver damage

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild hepatic impairment<br>120 mg olorofim | Drug: Olorofim<br>* single oral dose<br>* Other names: F901318;|
| Experimental: Moderate hepatic impairment<br>60 to 120 mg olorofim | Drug: Olorofim<br>* single oral dose<br>* Other names: F901318;|
| Active Comparator: Normal hepatic function<br>120 mg olorofim | Drug: Olorofim<br>* single oral dose<br>* Other names: F901318;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the time of the last quantifiable concentration (AUC 0-t) |  | 0-96 hours | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0-96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Plasma Concentration (Tmax) |  | 0-96 hours | 
| Apparent Elimination Half Life (t1/2) |  | 0-96 hours | 
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) |  | 0-96 hours | 
| Number of Participants With Treatment-Emergent Adverse Events |  | 10 days |