Single and Multiple Ascending Dose Study of CORT125236 in Healthy Participants

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05003713
• Other study ID #: CORT125236-150
• Secondary ID: 2021-001407-32
• Status: Completed
• Phase: Phase 1
• Start date: August 3, 2021
• Est. completion date: February 3, 2023

Study information

• Verified date: March 2023
• Source: Corcept Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: February 3, 2023
• Est. primary completion date: February 3, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• CORT125236
CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration
• Placebo matching CORT125236
Placebo matching CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration
• Prednisone
Prednisone tablet 25 mg (20 mg + 5 mg tablets) for oral administration

Locations

Country	Name	City	State
United Kingdom	Site 01	Ruddington	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Corcept Therapeutics

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Serum Cortisol Concentration		Before dosing on Days 1 and 14 (Part 2 MAD Cohorts)
Secondary	Plasma Adrenocorticotropic Hormone (ACTH) Concentration		Before dosing on Days 1 and 14 (Part 2 MAD Cohorts)
Secondary	Eosinophil Count		Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)
Secondary	Lymphocyte Count		Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)
Secondary	Neutrophil Count		Before dosing and at pre-specified time points up to 24 hours after dosing (Part 3, Period 1 and 2 PD Cohort)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Plasma Tumor Necrosis Factor Alpha (TNF-a) 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)
Secondary	Plasma Interleukin-1 Beta (IL-1ß) Concentration following ex vivo LPS Stimulation		Before dosing and 1, 2, and 4 hours after dosing (Part 3, Periods 1 and 2 PD Cohort)