Clinical trial NCT03067376: A Study Designed to See How [14C]-CORT125134 is Taken up, Broken Down and Removed From the Body
Official title: An Open-label, Single-dose Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Identification of Metabolite Structures for [14C]-CORT125134 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Absorption, distribution, metabolism, and excretion (ADME)
Metabolism
Metabolite Profiling
Excretion
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-03-01
Enrollment: 9
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The study was designed to evaluate how CORT125134 is taken up, broken down and removed from the body when given as an oral capsule to healthy subjects.

Detailed description: The study was conducted to determine the recovery of \[14C\]-CORT125134 after the administration of a single oral dose of \[14C\]-CORT125134, to determine the routes and rate of elimination of \[14C\]-CORT125134 and associated radioactivity from the body, and to measure concentrations of radioactivity in the blood. Additional objectives of the study were to determine the chemical structure of each significant metabolite in plasma, urine and feces. Safety and tolerability were assessed.

Eligibility criteria: Inclusion Criteria:

* Healthy males or healthy females of non-childbearing potential (surgically sterilized or postmenopausal \[defined as a woman of with at least a 12 month history of amenorrhea with a follicle-stimulating hormone (FSH) \>40 international units per liter (IU/L) in the absence of a reversible medical iatrogenic cause\])
* Age 30 to 65 years of age
* A history of regular bowel movements (averaging ≥1 and ≤3 stools per day)
* Must be willing and able to communicate and participate in the whole study
* Must provide written informed consent
* Male participants must agree to use an adequate method of contraception
* Participants are willing to abide by the study restrictions

Exclusion Criteria:

* Participation in a clinical research study within the previous 3 months
* Participants who have previously been enrolled in this study or participants who have previously been treated with CORT125134
* History of any drug or alcohol abuse in the past 2 years
* Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, 25 milliliter (mL) of 40% spirit or a 125 mL glass of wine)
* Current smokers and those who have smoked within the last 12 months; this includes cigarettes, e-cigarettes and nicotine replacement products. A breath carbon monoxide reading of greater than 10 parts per million (ppm)
* Females of childbearing potential (female participants must have a negative urine pregnancy test)
* Male Participants with pregnant partners
* Radiation exposure exceeding 5 millisievert (mSv) in the last 12 months or 10 mSv in the last 5 years. The measurement includes exposure from the present study, and diagnostic x rays and other medical exposures, but excludes background radiation. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999.
* Positive drugs of abuse test result
* Participants who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 grams per day paracetamol) or herbal remedies in the 14 days before study drug administration. Hormone replacement therapy is not permitted

Primary outcomes:
measure: Amount of radioactivity eliminated in urine
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Amount of radioactivity eliminated in feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Amount of radioactivity eliminated in urine and feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Cumulative amount of radioactivity eliminated in urine
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Cumulative amount of radioactivity eliminated in feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Cumulative amount of radioactivity eliminated in urine and feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Pharmacokinetics (PK) of total radioactivity: lag time (tlag)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: peak plasma concentration (Cmax)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: time to reach maximum observed concentration (tmax)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUClast)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: area under the plasma concentration-time curve from time zero to infinity (AUCinf)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCextrap)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve (lambda-z)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: elimination half-life (t1/2)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Metabolic profiling and structural identification in plasma, urine and feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
Secondary outcomes:
measure: Hematology
timeFrame: Screening, Day 1 pre-dose, Day 8
measure: Clinical chemistry
timeFrame: Screening, Day 1 pre-dose, Day 8
measure: Urinalysis
timeFrame: Screening, Day 1 pre-dose, Day 8
measure: Blood pressure
timeFrame: Screening, Day 1 pre-dose and 2 hours post-dose, Day 8
measure: Heart rate
timeFrame: Screening, Day 1 pre-dose and 2 hours post-dose, Day 8
measure: Electrocardiogram
timeFrame: Screening, Day 1 pre-dose and 2 hours post-dose, Day 8
measure: Percentage of subjects with adverse events
timeFrame: Screening to Day 28
measure: Physical examination
timeFrame: Screening and Day 8
measure: Tlag of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Cmax of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Tmax of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: AUClast of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: %AUCextrap of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: AUCinf of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Lambda-z of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: T1/2 of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Mean Residence Time (MRT) of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Apparent oral clearance (CL/F) of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Apparent volume of distribution (Vz/F) of CORT125134
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Number of metabolites >10% of circulating radioactivity in plasma
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Number of metabolites >10% of the dose in urine
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Number of metabolites >10% of the dose in feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical
state: Nottinghamshire
Study officials:
affiliation: Quotient Clinical
name: Pui Leung, MBChB
role: PRINCIPAL_INVESTIGATOR
References: