Single and Multiple Ascending Dose Study of CORT125236 in Healthy Participants

Corcept Therapeutics82 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Number of Participants with One or More Adverse Events

Time frame: Part 1 SAD Cohorts: up to Day 12; Part 2 MAD Cohorts: up to Day 25; Part 3 Cohort: up to Day 19

Secondary Outcomes

Maximum Plasma Concentration (Cmax) of CORT125236

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Before dosing on Days 1 and 14 (Part 2 MAD Cohorts)

Plasma Adrenocorticotropic Hormone (ACTH) Concentration

Time frame: Before dosing on Days 1 and 14 (Part 2 MAD Cohorts)

Eosinophil Count

Time frame: Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)

Lymphocyte Count

Time frame: Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)

Neutrophil Count

Time frame: 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

Time frame: Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)

Plasma Glucose

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Before dosing and 1, 2, and 4 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)

Single and Multiple Ascending Dose Study of CORT125236 in Healthy Participants

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes