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

Primary Purpose

Invasive Fungal Infections

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

Olorofim

About this trial

This is an interventional other trial for Invasive Fungal Infections

Eligibility Criteria

18 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

PRA Health Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort A (mass balance)

Cohort B (biliary evaluation)

Arm Description

evaluation of mass balance and metabolite profiling

evaluation of biliary elimination

Outcomes

Primary Outcome Measures

Mass balance

% dose recovered in urine and faeces

Metabolite profiling

number of metabolites in plasma, urine and faeces > 10% of circulating radioactivity

Secondary Outcome Measures

biliary elimination

radioactivity present in bile (ug equiv/g)

Maximum plasma concentration (Cmax) for olorofim, F902412 and total radioactivity

time of maximum plasma concentration (Tmax) for olorofim, F902412 and total radioactivity

elimination half life (t1/2) for olorofim, F902412 and total radioactivity

Area under plasma concentration curve (AUC) for olorofim, F902412 and total radioactivity

Number of subjects with treatment-related adverse events

Number of subjects with clinically significant change from baseline in vital signs, laboratory parameters, and electrocardiogram findings

Full Information

NCT ID

NCT04039880

First Posted

July 26, 2019

Last Updated

November 11, 2019

Sponsor

F2G Biotech GmbH

Collaborators

PRA Health Sciences

1. Study Identification

Unique Protocol Identification Number

NCT04039880

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

July 30, 2019 (Actual)

Primary Completion Date

September 30, 2019 (Actual)

Study Completion Date

September 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

F2G Biotech GmbH

Collaborators

PRA Health Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Invasive Fungal Infections

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort A (mass balance)

Arm Type

Experimental

Arm Description

evaluation of mass balance and metabolite profiling

Arm Title

Cohort B (biliary evaluation)

Arm Type

Experimental

Arm Description

evaluation of biliary elimination

Intervention Type

Drug

Intervention Name(s)

Olorofim

Other Intervention Name(s)

F901318

Intervention Description

single oral dose (120 mg, 3.7 MBq)

Primary Outcome Measure Information:

Title

Mass balance

Description

% dose recovered in urine and faeces

Time Frame

28 days

Title

Metabolite profiling

Description

number of metabolites in plasma, urine and faeces > 10% of circulating radioactivity

Time Frame

15 days

Secondary Outcome Measure Information:

Title

biliary elimination

Description

radioactivity present in bile (ug equiv/g)

Time Frame

5 days

Title

Maximum plasma concentration (Cmax) for olorofim, F902412 and total radioactivity

Time Frame

15 days

Title

time of maximum plasma concentration (Tmax) for olorofim, F902412 and total radioactivity

Time Frame

15 days

Title

elimination half life (t1/2) for olorofim, F902412 and total radioactivity

Time Frame

15 days

Title

Area under plasma concentration curve (AUC) for olorofim, F902412 and total radioactivity

Time Frame

15 days

Title

Number of subjects with treatment-related adverse events

Time Frame

28 days

Title

Number of subjects with clinically significant change from baseline in vital signs, laboratory parameters, and electrocardiogram findings

Time Frame

28 days

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jan Jaap van Lier, MD

Organizational Affiliation

PRA

Official's Role

Principal Investigator

Facility Information:

Facility Name

PRA Health Sciences

City

Groningen

ZIP/Postal Code

9728

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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