Single and Multiple Ascending Dose Study of CORT125236 in Healthy Participants

NCT ID: NCT05003713

Last Updated: 2023-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-03
• Study Completion Date: 2023-02-03

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

CORT125236

Intervention Type: DRUG

CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration

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.

Group Type: PLACEBO_COMPARATOR

Placebo matching CORT125236

Intervention Type: DRUG

Placebo matching CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration

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.

Group Type: EXPERIMENTAL

CORT125236

Intervention Type: DRUG

CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration

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.

Group Type: PLACEBO_COMPARATOR

Placebo matching CORT125236

Intervention Type: DRUG

Placebo matching CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration

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.

Group Type: EXPERIMENTAL

CORT125236

Intervention Type: DRUG

CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration

Prednisone

Intervention Type: DRUG

Prednisone tablet 25 mg (20 mg + 5 mg tablets) for oral administration

Interventions

CORT125236

CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration

Intervention Type: DRUG

Placebo matching CORT125236

Placebo matching CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration

Intervention Type: DRUG

Prednisone

Prednisone tablet 25 mg (20 mg + 5 mg tablets) for oral administration

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Corcept Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hazel Hunt, Ph.D.

Role: STUDY_DIRECTOR

Corcept Therapeutics

Locations

Site 01

Ruddington, Nottingham, United Kingdom

Countries

United Kingdom

Other Identifiers

2021-001407-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CORT125236-150

Identifier Type: -

Identifier Source: org_study_id