Clinical trial NCT05003713: Single and Multiple Ascending Dose Study of CORT125236 in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-08-12
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with One or More Adverse Events
timeFrame: 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:
measure: Maximum Plasma Concentration (Cmax) of CORT125236
timeFrame: 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)
measure: Time of Cmax (Tmax) of Plasma CORT125236
timeFrame: 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)
measure: Apparent Elimination Half-life (t1/2) of Plasma CORT125236
timeFrame: 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)
measure: Area Under the Plasma Concentration-time Curve (AUC) of CORT125236
timeFrame: 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)
measure: Serum Cortisol Concentration
timeFrame: Before dosing on Days 1 and 14 (Part 2 MAD Cohorts)
measure: Plasma Adrenocorticotropic Hormone (ACTH) Concentration
timeFrame: Before dosing on Days 1 and 14 (Part 2 MAD Cohorts)
measure: Eosinophil Count
timeFrame: Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)
measure: Lymphocyte Count
timeFrame: Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)
measure: Neutrophil Count
timeFrame: Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)
measure: Serum Osteocalcin Concentration
timeFrame: Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)
measure: Plasma Glucose
timeFrame: 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)
measure: Serum Insulin
timeFrame: 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)
measure: Plasma Tumor Necrosis Factor Alpha (TNF-α) Concentration following ex vivo Lipopolysaccharide (LPS) Stimulation
timeFrame: Before dosing and 1, 2, and 4 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)
measure: Plasma Interleukin-1 Beta (IL-1β) Concentration following ex vivo LPS Stimulation
timeFrame: Before dosing and 1, 2, and 4 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Site 01
state: Nottingham
Study officials:
affiliation: Corcept Therapeutics
name: Hazel Hunt, Ph.D.
role: STUDY_DIRECTOR
References: