Absorption, Metabolism and Excretion of 14C-olorofim in Man

Phase 1

Completed

• Conditions: Invasive Fungal Infections
• Interventions: Drug: Olorofim

• Registration Number: NCT04039880
• Lead Sponsor: F2G Biotech GmbH

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.

Study Timeline

• Study First Submitted: 2019-07-26
• Study First Submitted QC: 2019-07-29
• Study Start: 2019-07-30
• Study First Posted: 2019-07-31
• Status Verified: 2019-08
• Primary Completion: 2019-09-30
• Study Completion: 2019-09-30
• Last Update Submitted: 2019-11-11
• Last Update Posted: 2019-11-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort B (biliary evaluation)	Olorofim	evaluation of biliary elimination
Cohort A (mass balance)	Olorofim	evaluation of mass balance and metabolite profiling

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Maximum plasma concentration (Cmax) for olorofim, F902412 and total radioactivity	15 days
time of maximum plasma concentration (Tmax) for olorofim, F902412 and total radioactivity	15 days
Number of subjects with treatment-related adverse events	28 days
biliary elimination	5 days	radioactivity present in bile (ug equiv/g)
elimination half life (t1/2) for olorofim, F902412 and total radioactivity	15 days
Area under plasma concentration curve (AUC) for olorofim, F902412 and total radioactivity	15 days
Number of subjects with clinically significant change from baseline in vital signs, laboratory parameters, and electrocardiogram findings	28 days

Trial Locations

Locations (1)

PRA Health Sciences; 🇳🇱 Groningen, Netherlands