Single and Multiple Ascending Dose Study of CORT125236 in Healthy Participants

A Phase I Adaptive Dose, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered CORT125236 in Healthy Subjects, With an Optional Pharmacological Effects Cohort

This is a 3-part, first-in-human study of single ascending doses (SAD; Part 1) and multiple ascending doses (MAD; Part 2) of CORT125236 in healthy participants; Part 3 is optional, to investigate whether CORT125236 ameliorates the effects of prednisone on various pharmacodynamic (PD) endpoints. The 3 parts may not be conducted entirely sequentially provided that this is justified by the pharmacokinetic (PK) and safety data obtained from completed cohorts. The first MAD cohort will not start until data are available from at least 3 SAD levels to allow MAD administration to proceed. The decision on whether to start Part 3 can be made at any point after completion of 3 SAD levels, and will be based on achieving sufficiently high plasma CORT125236 exposure in Part 1 of the study.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: CORT125236; Drug: Placebo matching CORT125236; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Site 01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index 18.0 to 30.0 kg/m^2, inclusive
• Body weight ≤102 kg
• Willing to consume a high-fat breakfast, including pork
• Adheres to the contraception requirements of the protocol
• Additional criteria apply.

Exclusion Criteria:

• Received any investigational drug or device in a clinical research study within 90 days
• Evidence of current severe acute respiratory syndrome (SARS-CoV-2) infection
• History of any drug or alcohol abuse in the past 2 years; a confirmed positive drugs of abuse test result
• Regular alcohol consumption; a confirmed positive alcohol breath test at screening
• Current smoker; a confirmed positive breath carbon monoxide reading; current user of e-cigarettes and nicotine replacement products in the last 6 months
• Female of childbearing potential, pregnant, or breastfeeding
• Male participant with pregnant or lactating partners
• Clinically significant abnormal clinical chemistry, hematology or urinalysis result
• Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV)
• Active renal and/or hepatic disease
• History of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, gastrointestinal (GI), neurological or psychiatric disorder
• Any form of cancer in the 5 years (exceptions apply)
• History of adrenal insufficiency
• Have a condition that could be aggravated by glucocorticoid antagonism
• Donation or loss of greater than 400 mL of blood or plasma within the previous 3 months
• Currently using glucocorticoids or have a history of systemic glucocorticoid use in the last 12 months or 3 months for inhaled products
• Additional criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: SAD Cohorts A through F CORT125236; Cohorts will receive a single dose of CORT125236 lipid capsule formulation by mouth on Day 1 in a fasted or fed state. Cohort A will receive a 20-mg dose in a fasted state. Cohort B will receive a ≤3-fold increase in dose from Cohort A in a fasted state; the dose level and dose regimen (whether to split the dose) will be determined after evaluation of safety and PK data for Cohort A. Subsequent cohorts will receive a ≤3-fold increase in CORT125236 dose from the previous cohort in a fasted or fed state; the dose level, dose regimen, and prandial state will be determined after evaluation of safety and PK data from previous cohorts.	Drug: CORT125236; CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration
Placebo Comparator: Part 1: SAD Cohorts A through F Placebo; Cohorts will receive a single dose of placebo matching CORT125236 lipid capsule formulation by mouth on Day 1. The dose regimen and prandial state will be the same as those for the cohort members receiving CORT125236.	Drug: Placebo matching CORT125236; Placebo matching CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration
Experimental: Part 2: MAD Cohorts A through D CORT125236; Cohorts will receive once- or twice-daily doses of CORT125236 lipid capsule formulation by mouth for 14 days. The anticipated exposure will not exceed the highest exposure considered safe and well-tolerated during Part 1. The dose level, dose schedule, and prandial state for each cohort will be determined after evaluation of safety and PK data from Part 1 and preceding Part 2 cohorts.	Drug: CORT125236; CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration
Placebo Comparator: Part 2: MAD Cohorts A through D Placebo; Cohorts will receive once- or twice-daily doses of placebo matching CORT125236 lipid capsule formulation by mouth for 14 days. The dose regimen and prandial state will be the same as those for the cohort members receiving CORT125236.	Drug: Placebo matching CORT125236; Placebo matching CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration
Experimental: Part 3: Single Dose Pharmacodynamic Effect; In Period 1, participants will receive a single dose of prednisone 25 mg (20 mg + 5 mg) tablet by mouth on Day 1 in a fasted or fed state. After a 7-day washout, in Period 2, participants will receive a single dose of prednisone as in Period 1 plus a single dose of CORT125236 lipid capsule formulation by mouth on Day 1 in a fasted or fed state. The dose of CORT125236 and the prandial state will be determined after evaluation of safety and PK data from Part 1. Part 3 of the study is optional.	Drug: CORT125236; CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration; Drug: Prednisone; Prednisone tablet 25 mg (20 mg + 5 mg tablets) for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with One or More Adverse Events	Part 1 SAD Cohorts: up to Day 12; Part 2 MAD Cohorts: up to Day 25; Part 3 Cohort: up to Day 19

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) of CORT125236	Before dosing and at pre-specified time points up to Day 5 (Part 1 SAD Cohorts), or up to Day 18 (Part 2 MAD Cohorts)
Time of Cmax (Tmax) of Plasma CORT125236	Before dosing and at pre-specified time points up to Day 5 (Part 1 SAD Cohorts), or up to Day 18 (Part 2 MAD Cohorts)
Apparent Elimination Half-life (t1/2) of Plasma CORT125236	Before dosing and at pre-specified time points up to Day 5 (Part 1 SAD Cohorts), or up to Day 18 (Part 2 MAD Cohorts)
Area Under the Plasma Concentration-time Curve (AUC) of CORT125236	Before dosing and at pre-specified time points up to Day 5 (Part 1 SAD Cohorts), or up to Day 18 (Part 2 MAD Cohorts)
Serum Cortisol Concentration	Before dosing on Days 1 and 14 (Part 2 MAD Cohorts)
Plasma Adrenocorticotropic Hormone (ACTH) Concentration	Before dosing on Days 1 and 14 (Part 2 MAD Cohorts)
Eosinophil Count	Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)
Lymphocyte Count	Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)
Neutrophil Count	Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)
Serum Osteocalcin Concentration	Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)
Plasma Glucose	4 hours after dosing and immediately prior to a high-carbohydrate lunch, and approximately 2 hours after starting the lunch (Part 3, Period 1 and 2 PD Cohort)
Serum Insulin	4 hours after dosing and immediately prior to a high-carbohydrate lunch, and approximately 2 hours after starting the lunch (Part 3, Period 1 and 2 PD Cohort)
Plasma Tumor Necrosis Factor Alpha (TNF-α) Concentration following ex vivo Lipopolysaccharide (LPS) Stimulation	Before dosing and 1, 2, and 4 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)
Plasma Interleukin-1 Beta (IL-1β) Concentration following ex vivo LPS Stimulation	Before dosing and 1, 2, and 4 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)

Collaborators and Investigators

• Sponsor: Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2021
• Primary Completion (Actual): February 3, 2023
• Study Completion (Actual): February 3, 2023

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Cortisone
• Other Study ID Numbers: CORT125236-150; 2021-001407-32 (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