Absolute Bioavailability and Metabolism Study of CORT118335 in Healthy Male Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: CORT118335 Oral; Drug: 14C-CORT118335 intravenous; Drug: 14C-CORT118335 oral

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; 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; CORT118335 900 mg spray-dried dispersion in bottle and vehicle for oral administration; Other Names: Treatment A; Drug: 14C-CORT118335 intravenous; 14C-CORT118335 solution for infusion 100 µg containing not more than 37 kiloBequerel (1 µCi) 14C; Other Names: Treatment B
Experimental: Part 2; 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; 14C-CORT118335 oral solution 150 mg containing not more than 3.3 megaBequerel (90 µCi) 14C; Other Names: Treatment C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2018
• Primary Completion (Actual): March 24, 2019
• Study Completion (Actual): March 24, 2019

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): June 11, 2019
• Last Update Submitted That Met QC Criteria: June 10, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Inflammatory Agents; Cortisone
• Other Study ID Numbers: CORT118335-851; 2018-001507-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No