Single and Multiple Ascending Dose Study of CORT125236 in Healthy Participants

NCT05003713 | Completed Phase 1

• 2 other identifiers: CORT125236-1502021-001407-32
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• 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)

• 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)

Study Arms (5)

Part 1: SAD Cohorts A through F CORT125236

EXPERIMENTAL

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.

Drug: CORT125236

Part 1: SAD Cohorts A through F Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo matching CORT125236

Part 2: MAD Cohorts A through D CORT125236

EXPERIMENTAL

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.

Drug: CORT125236

Part 2: MAD Cohorts A through D Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo matching CORT125236

Part 3: Single Dose Pharmacodynamic Effect

EXPERIMENTAL

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.

Drug: CORT125236; Drug: Prednisone

Interventions

CORT125236 DRUG

CORT125236 Lipid Capsule Formulation 10-60 mg for oral administration

Part 1: SAD Cohorts A through F CORT125236; Part 2: MAD Cohorts A through D CORT125236; Part 3: Single Dose Pharmacodynamic Effect

Placebo matching CORT125236 DRUG

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

Part 1: SAD Cohorts A through F Placebo; Part 2: MAD Cohorts A through D Placebo

Prednisone DRUG

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

Part 3: Single Dose Pharmacodynamic Effect

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Corcept Therapeutics: lead

Study Sites (1)

Site 01

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

Prednisone

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Hazel Hunt, Ph.D.

  Corcept Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 12, 2021
• Study Start: August 3, 2021
• Primary Completion: February 3, 2023
• Study Completion: February 3, 2023
• Last Updated: March 22, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)