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

Invasive Fungal Infections Clinical Trial

— hAME  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04039880
• Other study ID #: F901318-01-09
• Status: Completed
• Phase: Phase 1
• Start date: July 30, 2019
• Est. completion date: September 30, 2019

Study information

• Verified date: August 2019
• Source: F2G Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Invasive Fungal Infections
• Mycoses

Intervention

Drug:
• Olorofim
single oral dose (120 mg, 3.7 MBq)

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
F2G Ltd.	PRA Health Sciences

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mass balance	% dose recovered in urine and faeces	28 days
Primary	Metabolite profiling	number of metabolites in plasma, urine and faeces > 10% of circulating radioactivity	15 days
Secondary	biliary elimination	radioactivity present in bile (ug equiv/g)	5 days
Secondary	Maximum plasma concentration (Cmax) for olorofim, F902412 and total radioactivity		15 days
Secondary	time of maximum plasma concentration (Tmax) for olorofim, F902412 and total radioactivity		15 days
Secondary	elimination half life (t1/2) for olorofim, F902412 and total radioactivity		15 days
Secondary	Area under plasma concentration curve (AUC) for olorofim, F902412 and total radioactivity		15 days
Secondary	Number of subjects with treatment-related adverse events		28 days
Secondary	Number of subjects with clinically significant change from baseline in vital signs, laboratory parameters, and electrocardiogram findings		28 days