Clinical trial NCT04039880: Absorption, Metabolism and Excretion of 14C-olorofim in Man
Official title: An Open-Label, Single-Dose, Single-Period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-Olorofim Administered Via the Oral Route to Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Invasive Fungal Infections
Lead sponsor: F2G Biotech GmbH
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2019-07-31
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mass balance
timeFrame: 28 days
measure: Metabolite profiling
timeFrame: 15 days
Secondary outcomes:
measure: biliary elimination
timeFrame: 5 days
measure: Maximum plasma concentration (Cmax) for olorofim, F902412 and total radioactivity
timeFrame: 15 days
measure: time of maximum plasma concentration (Tmax) for olorofim, F902412 and total radioactivity
timeFrame: 15 days
measure: elimination half life (t1/2) for olorofim, F902412 and total radioactivity
timeFrame: 15 days
measure: Area under plasma concentration curve (AUC) for olorofim, F902412 and total radioactivity
timeFrame: 15 days
measure: Number of subjects with treatment-related adverse events
timeFrame: 28 days
measure: Number of subjects with clinically significant change from baseline in vital signs, laboratory parameters, and electrocardiogram findings
timeFrame: 28 days
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRA Health Sciences
Study officials:
affiliation: PRA
name: Jan Jaap van Lier, MD
role: PRINCIPAL_INVESTIGATOR
References: