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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04039880
Recruitment Status : Completed
First Posted : July 31, 2019
Last Update Posted : November 13, 2019
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
F2G Ltd.

Tracking Information
First Submitted Date  ICMJE July 26, 2019
First Posted Date  ICMJE July 31, 2019
Last Update Posted Date November 13, 2019
Actual Study Start Date  ICMJE July 30, 2019
Actual Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2019)
  • Mass balance [ Time Frame: 28 days ]
    % dose recovered in urine and faeces
  • Metabolite profiling [ Time Frame: 15 days ]
    number of metabolites in plasma, urine and faeces > 10% of circulating radioactivity
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2019)
  • biliary elimination [ Time Frame: 5 days ]
    radioactivity present in bile (ug equiv/g)
  • Maximum plasma concentration (Cmax) for olorofim, F902412 and total radioactivity [ Time Frame: 15 days ]
  • time of maximum plasma concentration (Tmax) for olorofim, F902412 and total radioactivity [ Time Frame: 15 days ]
  • elimination half life (t1/2) for olorofim, F902412 and total radioactivity [ Time Frame: 15 days ]
  • Area under plasma concentration curve (AUC) for olorofim, F902412 and total radioactivity [ Time Frame: 15 days ]
  • Number of subjects with treatment-related adverse events [ Time Frame: 28 days ]
  • Number of subjects with clinically significant change from baseline in vital signs, laboratory parameters, and electrocardiogram findings [ Time Frame: 28 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Absorption, Metabolism and Excretion of 14C-olorofim in Man
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Invasive Fungal Infections
Intervention  ICMJE Drug: Olorofim
single oral dose (120 mg, 3.7 MBq)
Other Name: F901318
Study Arms  ICMJE
  • Experimental: Cohort A (mass balance)
    evaluation of mass balance and metabolite profiling
    Intervention: Drug: Olorofim
  • Experimental: Cohort B (biliary evaluation)
    evaluation of biliary elimination
    Intervention: Drug: Olorofim
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 29, 2019)
12
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 30, 2019
Actual Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04039880
Other Study ID Numbers  ICMJE F901318-01-09
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party F2G Ltd.
Study Sponsor  ICMJE F2G Ltd.
Collaborators  ICMJE PRA Health Sciences
Investigators  ICMJE
Principal Investigator: Jan Jaap van Lier, MD PRA
PRS Account F2G Ltd.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP