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

• ClinicalTrials.gov Identifier: NCT04039880
• Recruitment Status: Completed
• First Posted: July 31, 2019
• Last Update Posted: November 13, 2019
• Sponsor: F2G Biotech GmbH
• Collaborator: PRA Health Sciences
• Information provided by (Responsible Party): F2G Biotech GmbH

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Invasive Fungal Infections	Drug: Olorofim	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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
• Actual Study Start Date: July 30, 2019
• Actual Primary Completion Date: September 30, 2019
• Actual Study Completion Date: September 30, 2019

Arms and Interventions

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 Name: F901318
Experimental: Cohort B (biliary evaluation); evaluation of biliary elimination	Drug: Olorofim; single oral dose (120 mg, 3.7 MBq); Other Name: F901318

Outcome Measures

Primary Outcome Measures :

1. Mass balance [ Time Frame: 28 days ]
   % dose recovered in urine and faeces
2. Metabolite profiling [ Time Frame: 15 days ]
   number of metabolites in plasma, urine and faeces > 10% of circulating radioactivity

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Netherlands

PRA Health Sciences

Groningen, Netherlands, 9728

Sponsors and Collaborators

F2G Biotech GmbH

PRA Health Sciences

Investigators

• Principal Investigator: Jan Jaap van Lier, MD; PRA

More Information

• Responsible Party: F2G Biotech GmbH
• ClinicalTrials.gov Identifier: NCT04039880
• Other Study ID Numbers: F901318-01-09
• First Posted: July 31, 2019
• Last Update Posted: November 13, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Mycoses; Invasive Fungal Infections; Bacterial Infections and Mycoses; Infections; Olorofim; Antifungal Agents; Anti-Infective Agents