Healthy
Conditions
Brief summary
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.
Interventions
DRUGCORT125236
CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration
DRUGPlacebo matching CORT125236
Placebo matching CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration
DRUGPrednisone
Prednisone tablet 25 mg (20 mg + 5 mg tablets) for oral administration
Sponsors
Corcept Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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) |
| 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) |
| 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) |
| Lymphocyte Count | Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort) |
Countries
United Kingdom
Outcome results
None listed