Invasive Fungal Infections
Conditions
Brief summary
Single-centre, open-label, non-randomised, single dose study in 2 cohorts of healthy subjects. It is planned to enrol 6 healthy male subjects in Cohort A (standard mass balance and metabolite profiling cohort) and up to 6 subjects in Cohort B (biliary evaluation cohort); each subject will receive a single oral administration of 120 mg \[14C\]-olorofim oral solution containing approximately 3.7 MBq (100 µCi).
Detailed description
Subjects will be screened up to 28 days prior to dosing and eligible subjects will be admitted to the Clinical Research Unit (CRU) on the day prior to dosing (Day-1). Each subject will be dosed on the morning of Day 1 after an overnight fast. Cohort A: Subjects will remain resident in the CRU up to 336 h post-dose (Day 15), with whole blood, plasma, urine and faeces collected throughout this period. There may be up to two further 24 h residency periods (Days 21 to 22 and Days 28 to 29) for collection of plasma, urine and faeces if discharge criteria are not met. Cohorts B1 and B2: Subjects will remain resident in the CRU up to 96 h post-dose (Day 5) for collection of plasma, urine, faeces and bile. Subjects will return for a short follow-up visit on Day 10. Cohort B1 subjects will have bile sampling up to 6 h postdose and Cohort B2 subjects will have bile sampling up to 12 h postdose. Cohort B divided into 2 sub-cohorts for logistical reasons only.
Interventions
DRUGOlorofim
single oral dose (120 mg, 3.7 MBq)
Sponsors
PRA Health Sciences
F2G Biotech GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy males age 18 to 55 years of age with body mass index of 18 to 30 kg/m2 (inclusive), and a body weight of 50 to 100 kg (inclusive). * Subjects must be in good health as determined by a medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory evaluations (congenital non haemolytic hyperbilirubinaemia is NOT acceptable). * Must have regular bowel movements (ie, average stool production of ≥1 and ≤3 stools per day).
Exclusion criteria
* 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 * Subjects who have received any prescribed systemic or topical medication within 14 days of the dose administration * Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the 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 the dose administration * Current smokers and those who have smoked or used nicotine containing products (eg electronic cigarettes) within the 3 months prior to check-in. * Radiation exposure, including that from the present study exceeding 1 mSv in the last 12 months or 5 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mass balance | 28 days | % dose recovered in urine and faeces |
| Metabolite profiling | 15 days | number of metabolites in plasma, urine and faeces \> 10% of circulating radioactivity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| time of maximum plasma concentration (Tmax) for olorofim, F902412 and total radioactivity | 15 days | — |
| elimination half life (t1/2) for olorofim, F902412 and total radioactivity | 15 days | — |
| biliary elimination | 5 days | radioactivity present in bile (ug equiv/g) |
| Number of subjects with treatment-related adverse events | 28 days | — |
| Number of subjects with clinically significant change from baseline in vital signs, laboratory parameters, and electrocardiogram findings | 28 days | — |
| Area under plasma concentration curve (AUC) for olorofim, F902412 and total radioactivity | 15 days | — |
| Maximum plasma concentration (Cmax) for olorofim, F902412 and total radioactivity | 15 days | — |
Countries
Netherlands
Outcome results
None listed