CORT125134 Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)

August 7, 2019 updated by: Corcept Therapeutics

A Phase I Adaptive Dose, Double-Blind, Placebo-Controlled, SAD and MAD Study to Measure the Safety, Tolerability, Pharmacokinetics and Pharmacological Effects of Orally Administered CORT125134 in Healthy Subjects

The purpose of this study is to evaluate the dose-related safety, tolerability, pharmacokinetics (PK) and pharmacological effects (PD) of CORT125134 and its active metabolite CORT125201 after single and multiple ascending oral doses of CORT125134 in healthy participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a 3-part, single-center study of single and multiple ascending doses of CORT125134 in healthy participants.

Part I is a single dose study. Initially, participants will be enrolled sequentially into 1 of up to 6 cohorts, each containing 10 participants, in a double-blind, randomized, placebo-controlled assessment of single-ascending doses (SAD) of CORT125134. Within each cohort, 8 participants will be randomly assigned to receive a single dose of CORT125134, and 2 participants will be randomly assigned to receive a single dose of matching placebo. Thereafter, Cohort 7 will be a food-effect cohort, in which all 8 participants will receive a single dose of CORT125134 after a high-fat breakfast (open label). Cohorts 8 and 9 will be pharmacological effect cohorts, in each of which 10 participants will receive a challenge agent (prednisone, 25 mg) alone on Day -19; with an active comparator (mifepristone, 600 mg) on Day -12, and with CORT125134 on Day 1 in an open-label single sequence crossover design. Pharmacological effects will be explored by measuring effects on peripheral blood eosinophil, lymphocyte and neutrophil counts, serum osteocalcin, assay of messenger ribonucleic acid (mRNA) expression of FK506 Binding Protein 5 (FKBP5) and Glucocorticoid-induced Leucine Zipper (GILZ) in whole blood (proof of pharmacological effect Cohort 8) and by measuring effects on oral glucose tolerance (proof of concept Cohort 9).

Part 2 and 3 will be double-blind, randomized, placebo-controlled assessments of multiple oral ascending doses (MAD) of CORT125134. Participants will be enrolled sequentially into 1 of up to 4 cohorts (Cohorts 10-13), each containing 12 participants. Within each cohort, 9 participants will be randomly assigned to receive CORT125134 and 3 participants to receive matching placebo daily for 14 days (Days 1-14). The effects of CORT125134 on response to prednisone challenge will be additionally explored in Cohorts 12 and 13 in a single sequence crossover, with prednisone being given alone on Day -5 and in combination with CORT125134 or placebo on Day 14.

Throughout the study, routine safety tests and assessments of PK (CORT125134 and CORT125201) will be performed, and changes in serum cortisol and plasma adrenocorticotrophic hormone (ACTH) measured.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
130

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG11 6JS
        • Quotient Clinical

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 56 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Provide written informed consent
  • Weight <= 102 kilogram (kg); body mass index (BMI) 18-30 kg/meter squared
  • Morning serum cortisol in reference range
  • Willing and able to communicate, participate in the whole study and to abide by study restrictions including use of contraception

Exclusion Criteria:

  • Participation in any clinical research study, received treatment with any investigational drug or device, or donated blood within the previous 3 months
  • Has a history of alcoholism, substance abuse, or drug abuse within 1 year; positive screen for alcohol or drugs of abuse
  • Current smokers, smoked and/or used tobacco and/or nicotine-containing products within 6 months, or positive screen for carbon monoxide
  • Females of childbearing potential, pregnant or breastfeeding, and/or with a positive pregnancy test
  • Has a condition that could be aggravated by glucocorticoid blockade or activation
  • Has clinically relevant abnormal findings on vital signs, physical examination, laboratory screening tests, or 12-lead electrocardiogram (ECG)
  • Has history of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, chronic respiratory, gastrointestinal or neurological disease
  • Has used systemic glucocorticoids within 12 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SAD Cohorts 1 through 6
Participants will receive single doses of 5 mg up to 400 mg of CORT125134 (capsule) in a dose escalation format. The doses selected will be subject to amendment based on emerging data.
Drug: CORT125134
Oral capsules
Placebo Comparator: SAD Cohorts 1 through 6 Placebo
Participants will receive single doses of Matching Placebo of CORT125134 (capsule).
Drug: Matching Placebo of CORT125134
Placebo
Experimental: Food Effect Cohort 7
Participants will receive a single dose of CORT125134 (capsule) with a standard high fat breakfast. The dose will be chosen such that it has been previously administered in a prior SAD cohort.
Drug: CORT125134
Oral capsules
Experimental: Pharmacological Effect Cohort 8
Participants will receive a single dose of 25 mg of prednisone on Day -19; a single dose of 25 mg prednisone and 600 mg of mifepristone on Day -12; and a single dose of 25 mg prednisone and a single dose of CORT125134 on Day 1. The dose of CORT125134 will be chosen such that it has been previously administered in a prior SAD cohort.
Drug: CORT125134
Oral capsules
Drug: Mifepristone
Active comparator
Drug: Prednisone
Challenge agent
Experimental: Proof of Concept (POC) Cohort 9
Participants will receive a single dose of 25 mg of prednisone on Day -19; a single dose of 25 mg of prednisone and 600 mg of mifepristone on Day -12; and a single dose of 25 mg prednisone and a single dose of CORT125134 on Day 1. An oral glucose tolerance test will be administered on each study day. The dose of CORT125134 will be chosen such that it has been previously administered in a prior SAD cohort.
Drug: Glucose
Drug: CORT125134
Oral capsules
Drug: Mifepristone
Active comparator
Drug: Prednisone
Challenge agent
Experimental: MAD Cohorts 10 and 11
Participants will receive the selected dose of CORT125134 (capsule) following receipt of data from Cohorts 1-9 up to a maximum frequency of twice a day for a total of 14 days.
Drug: CORT125134
Oral capsules
Placebo Comparator: MAD Cohorts 10 and 11 Placebo
Participants will receive Matching Placebo of CORT125134 (capsule) up to a maximum frequency of twice a day for a total of 14 days.
Drug: Matching Placebo of CORT125134
Placebo
Experimental: MAD of PoPE Cohorts 12 and 13
Proof of Pharmacological Effect (PoPE+POC). Participants will receive 25 mg of prednisone (both cohorts) and an oral glucose tolerance test (Cohort 13 only) on Day -5. Participants will then receive the selected dose of CORT125134 (capsule) for a total of 13 days. Participants may either receive a higher dose level than previously administered or a repeat of a dose level given in 1 of the previous 2 MAD Cohorts. Participants will then receive 25 mg of prednisone (both cohorts) and an oral glucose tolerance test (Cohort 13 only) on Day 14.
Drug: Glucose
Drug: CORT125134
Oral capsules
Drug: Prednisone
Challenge agent
Placebo Comparator: MAD of PoPE Cohort 12 and 13 Placebo
Participants will receive 25 mg of prednisone (both cohorts) and an oral glucose tolerance test (Cohort 13 only) on Day -5. Participants will then receive the Matching Placebo of CORT125134 (capsule) for a total of 13 days. Participants will then receive 25 mg of prednisone (both cohorts) and an oral glucose tolerance test (Cohort 13 only) on Day 14.
Drug: Glucose
Drug: Matching Placebo of CORT125134
Placebo
Drug: Prednisone
Challenge agent

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Incidence of Treatment-Emergent Adverse Events (AEs) (Safety and Tolerability) of CORT125134
Time Frame: Single dose Cohorts 1-9 Day 1 to Day 15; MAD Cohorts 10-13 Day 1 to Day 28/Day 24 (Cohort 13)
Single dose Cohorts 1-9 Day 1 to Day 15; MAD Cohorts 10-13 Day 1 to Day 28/Day 24 (Cohort 13)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
QT internal corrected for heart rate using Fridericia's formula (QTcF) exposure-response analysis
Time Frame: SAD Cohorts 1-6: Pre dose through 24 hours post dose; MAD Cohorts: Pre first dose through 24 hours post final dose of Investigational Medicinal Product (IMP)
SAD Cohorts 1-6: Pre dose through 24 hours post dose; MAD Cohorts: Pre first dose through 24 hours post final dose of Investigational Medicinal Product (IMP)
CORT125134 Pharmacokinetic (PK) of total lag time (Tlag)
Time Frame: Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
CORT125134 PK of peak plasma concentration (Cmax)
Time Frame: Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
CORT125134 PK of time to reach maximum observed concentration (Tmax)
Time Frame: Single dose Cohorts Day 1 to Day 15; MAD Cohorts 10-12 Day 1 to Day 28/24 (Cohort 13)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts 10-12 Day 1 to Day 28/24 (Cohort 13)
CORT125134 PK of area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUClast)
Time Frame: Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
CORT125201 PK of peak plasma concentration (Cmax)
Time Frame: Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
CORT125201 PK time Lag (Tlag)
Time Frame: Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
CORT125201 PK of time to reach maximum observed concentration (Tmax)
Time Frame: Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
CORT125201 PK of area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUClast)
Time Frame: Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Say 28/24 (Cohort 13)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Say 28/24 (Cohort 13)
Eosinophil count
Time Frame: Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Lymphocyte count
Time Frame: Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Neutrophil count
Time Frame: Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Osteocalcin
Time Frame: Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
FKBP5 expression
Time Frame: Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Glucocorticoid-induced leucine zipper (GILZ) expression
Time Frame: Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Single dose Cohort 8 Days -19 to Day 2; MAD Cohorts 12 and 13 Days -5 to Day 15
Glucose tolerance
Time Frame: Single dose Cohort 9 Days -19 to Day 2; MAD Cohort 13 Days -5 to Day 15
Single dose Cohort 9 Days -19 to Day 2; MAD Cohort 13 Days -5 to Day 15
Serum cortisol
Time Frame: SAD Cohorts 1-6: Pre dose to Day 15; MAD Cohorts 10-11: Pre dose to Day 28
SAD Cohorts 1-6: Pre dose to Day 15; MAD Cohorts 10-11: Pre dose to Day 28
Plasma adrenocorticotrophic hormone (ACTH)
Time Frame: SAD Cohorts 1-6: Pre dose to Day 15; MAD Cohorts 10-11: Pre dose to Day 28
SAD Cohorts 1-6: Pre dose to Day 15; MAD Cohorts 10-11: Pre dose to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Corcept Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Pui Leung, Quotient Clinical

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CORT125134-120
  • 2014-001951-21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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