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

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

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).

Study Overview

• Status: Completed
• Conditions: Invasive Fungal Infections
• Intervention / Treatment: Drug: Olorofim

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728
    • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (mass balance); evaluation of mass balance and metabolite profiling	Drug: Olorofim; single oral dose (120 mg, 3.7 MBq); Other Names: F901318
Experimental: Cohort B (biliary evaluation); evaluation of biliary elimination	Drug: Olorofim; single oral dose (120 mg, 3.7 MBq); Other Names: F901318

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mass balance	% dose recovered in urine and faeces	28 days
Metabolite profiling	number of metabolites in plasma, urine and faeces > 10% of circulating radioactivity	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
biliary elimination	radioactivity present in bile (ug equiv/g)	5 days
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
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 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

Collaborators and Investigators

• Sponsor: F2G Biotech GmbH
• Collaborators: PRA Health Sciences
• Investigators: Principal Investigator: Jan Jaap van Lier, MD, PRA

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2019
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: July 29, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): November 13, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Invasive Fungal Infections; Anti-Infective Agents; Antifungal Agents; Olorofim
• Other Study ID Numbers: F901318-01-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No