Clinical trial NCT03878264: Absolute Bioavailability and Metabolism Study of CORT118335 in Healthy Male Participants
Official title: An Open-label, 2-part Study Designed to Assess the Absolute Bioavailability of CORT118335 and Determine the Mass Balance Recovery, Absorption, Metabolism and Elimination, and Metabolite Profile and Identification of Metabolite Structures of [14C]-CORT118335 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-03-18
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: This study will evaluate the absolute bioavailability of CORT118335 and determine the mass balance recovery, absorption, metabolism and elimination, and metabolite profile and identification of metabolite structures following a single oral dose of CORT118335 in healthy male participants.


Eligibility criteria: Inclusion Criteria:

* Age 18 to 65 years of age for Part 1 and 30 to 65 years of age for Part 2
* Body mass index of 18.0 to 30.0 kg/m\^2
* Provide written informed consent
* Have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day) for Part 2
* Adhere to the contraception requirements.

Exclusion Criteria:

* Have received any investigational medicine in a clinical research study within the previous 3 months or CORT118335 at any time
* Employees or immediate family members of employees of the study site or Sponsor
* Have a pregnant partner
* History of abuse of any drug or alcohol, or regularly consume more than 21 units alcohol/week
* Smokers or users of e-cigarettes and nicotine replacement products within the last 6 months
* Occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017; greater than background radiation exposure from other sources exceeding 5 milliSieverts (mSv) in the last 12 months or 10 mSv in the last 5 years
* Clinically significant abnormal results of clinical laboratory safety tests, electrocardiogram, or measurement of heart rate and blood pressure
* History of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, neurological, or gastrointestinal disease
* History and/or symptoms of adrenal insufficiency or any condition that could be aggravated by glucocorticoid blockade (e.g., an autoimmune disease; allergy requiring treatment)
* Donation or loss of greater than 400 mL of blood within the past 3 months
* Has consumed liquorice or other glycyrrhetic acid derivatives regularly in the past 6 months
* Are taking, or have taken, any prescribed, over-the-counter drug or vitamins/herbal remedies within 14 days (longer restrictions apply for some medicines).

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Primary outcomes:
measure: Absolute Oral Bioavailability (F) of CORT118335
timeFrame: Predose and at pre-specified time points up to Day 12
measure: Mass Balance Recovery in Excreta After a Single Oral Dose of 14C-CORT118335
timeFrame: Until the mass balance criteria have been met by all participants (estimated Day 17)
measure: Mass Balance Recovery in Urine After a Single Oral Dose of 14C-CORT118335
timeFrame: Until the mass balance criteria have been met by all participants (estimated Day 17)
measure: Mass Balance Recovery in Feces After a Single Oral Dose of 14C-CORT118335
timeFrame: Until the mass balance criteria have been met by all participants (estimated Day 17)
Secondary outcomes:
measure: Pharmacokinetics (PK) of Total Radioactivity after Oral Dosing: Peak Plasma Concentration (Cmax)
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Total Radioactivity in Plasma after Oral Dosing: Time from Dosing to Cmax (tmax)
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Total Radioactivity after Oral Dosing: Area Under the Plasma Concentration-time Curve from Zero Time to Time of the Last Measurable Concentration (AUC0-last)
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Total Radioactivity in Plasma after Oral Dosing: Apparent Elimination Half-life (t1/2)
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Total Radioactivity in Plasma after Oral Dosing: Mean Residence Time (MRT)
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Plasma CORT118335 after Oral Dosing: Cmax
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Plasma CORT118335 after Oral Dosing: Tmax
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Plasma CORT118335 after Oral Dosing: AUC0-last
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Plasma CORT118335 after Oral Dosing: MRT
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: PK of Plasma 14C-CORT118335 after IV Dosing: Cmax
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Plasma 14C-CORT118335 after IV Dosing: AUC0-last
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Plasma 14C-CORT118335 after IV Dosing: t1/2
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Plasma 14C-CORT118335 after IV Dosing: Total Clearance (CL)
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Plasma 14C-CORT118335 after IV Dosing: MRT
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Total Radioactivity in Plasma after IV Dosing: Cmax
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Total Radioactivity in Plasma after IV Dosing: AUC0-last
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Total Radioactivity in Plasma after IV Dosing: t1/2
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Total Radioactivity in Plasma after IV Dosing: CL
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK of Total Radioactivity in Plasma after IV Dosing: MRT
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: PK in Plasma after IV Dosing: AUC0-last for 14C-CORT118335 / AUC0-last for Total Radioactivity
timeFrame: Pre-dose and at pre-specified time points up to Day 12 after dosing
measure: Distribution of Total Radioactivity into Red Blood Cells after Oral Dosing
timeFrame: Pre-dose and at pre-specified time points up to Day 15 after dosing
measure: Number of CORT118335 Metabolites Accounting for >10% of Total Radioactivity Detected in Plasma, Urine, and Feces
timeFrame: Until the mass balance criteria have been met by all participants (estimated Day 17)
measure: Percentage of Participants with One or More Adverse Events
timeFrame: Until the mass balance criteria have been met by all participants (estimated Day 17)
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Quotient Sciences
state: Nottingham
Study officials:
affiliation: Quotient Sciences
name: Sharan Sidhu, MBChB, BAO, MRCS, MFPM
role: PRINCIPAL_INVESTIGATOR
References: