Absolute Bioavailability and Metabolism Study of CORT118335 in Healthy Male Participants

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: CORT118335 Oral
* Drug: 14C-CORT118335 intravenous
* Drug: 14C-CORT118335 oral


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>On Day 1, participants will receive a single oral dose of CORT118335 900 mg (Treatment A) after an overnight fast, and a 15-minute intravenous infusion of a microdose of 14C-CORT118335 (Treatment B) beginning 2 hours 45 minutes after the oral dose is administered. | Drug: CORT118335 Oral<br>* CORT118335 900 mg spray-dried dispersion in bottle and vehicle for oral administration<br>* Other names: Treatment A;Drug: 14C-CORT118335 intravenous<br>* 14C-CORT118335 solution for infusion 100 µg containing not more than 37 kiloBequerel (1 µCi) 14C<br>* Other names: Treatment B;|
| Experimental: Part 2<br>On Day 1, participants will receive a single oral dose of 14C-CORT118335 150 mg (Treatment C) after an overnight fast. | Drug: 14C-CORT118335 oral<br>* 14C-CORT118335 oral solution 150 mg containing not more than 3.3 megaBequerel (90 µCi) 14C<br>* Other names: Treatment C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Oral Bioavailability (F) of CORT118335 |  | Predose and at pre-specified time points up to Day 12 | 
| Mass Balance Recovery in Excreta After a Single Oral Dose of 14C-CORT118335 |  | Until the mass balance criteria have been met by all participants (estimated Day 17) | 
| Mass Balance Recovery in Urine After a Single Oral Dose of 14C-CORT118335 |  | Until the mass balance criteria have been met by all participants (estimated Day 17) | 
| Mass Balance Recovery in Feces After a Single Oral Dose of 14C-CORT118335 |  | Until the mass balance criteria have been met by all participants (estimated Day 17) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of Total Radioactivity after Oral Dosing: Peak Plasma Concentration (Cmax) |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| PK of Total Radioactivity in Plasma after Oral Dosing: Time from Dosing to Cmax (tmax) |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| 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) |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| PK of Total Radioactivity in Plasma after Oral Dosing: Apparent Elimination Half-life (t1/2) |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| PK of Total Radioactivity in Plasma after Oral Dosing: Mean Residence Time (MRT) |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| PK of Plasma CORT118335 after Oral Dosing: Cmax |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| PK of Plasma CORT118335 after Oral Dosing: Tmax |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| PK of Plasma CORT118335 after Oral Dosing: AUC0-last |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| PK of Plasma CORT118335 after Oral Dosing: MRT |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| PK of Plasma 14C-CORT118335 after IV Dosing: Cmax |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Plasma 14C-CORT118335 after IV Dosing: AUC0-last |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Plasma 14C-CORT118335 after IV Dosing: t1/2 |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Plasma 14C-CORT118335 after IV Dosing: Total Clearance (CL) |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Plasma 14C-CORT118335 after IV Dosing: MRT |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Total Radioactivity in Plasma after IV Dosing: Cmax |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Total Radioactivity in Plasma after IV Dosing: AUC0-last |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Total Radioactivity in Plasma after IV Dosing: t1/2 |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Total Radioactivity in Plasma after IV Dosing: CL |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK of Total Radioactivity in Plasma after IV Dosing: MRT |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| PK in Plasma after IV Dosing: AUC0-last for 14C-CORT118335 / AUC0-last for Total Radioactivity |  | Pre-dose and at pre-specified time points up to Day 12 after dosing | 
| Distribution of Total Radioactivity into Red Blood Cells after Oral Dosing |  | Pre-dose and at pre-specified time points up to Day 15 after dosing | 
| Number of CORT118335 Metabolites Accounting for >10% of Total Radioactivity Detected in Plasma, Urine, and Feces |  | Until the mass balance criteria have been met by all participants (estimated Day 17) | 
| Percentage of Participants with One or More Adverse Events |  | Until the mass balance criteria have been met by all participants (estimated Day 17) |