CORT125134 Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)
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
2 other identifiers
interventional
130
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 healthy
Started Sep 2014
Longer than P75 for phase_1 healthy
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2015
CompletedFirst Submitted
Initial submission to the registry
February 21, 2017
CompletedFirst Posted
Study publicly available on registry
April 26, 2018
CompletedAugust 9, 2019
August 1, 2019
1.2 years
February 21, 2017
August 7, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence of Treatment-Emergent Adverse Events (AEs) (Safety and Tolerability) of CORT125134
Single dose Cohorts 1-9 Day 1 to Day 15; MAD Cohorts 10-13 Day 1 to Day 28/Day 24 (Cohort 13)
Secondary Outcomes (18)
QT internal corrected for heart rate using Fridericia's formula (QTcF) exposure-response analysis
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)
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)
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)
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)
Single dose Cohorts Day 1 to Day 15; MAD Cohorts Day 1 to Day 28/24 (Cohort 13)
- +13 more secondary outcomes
Study Arms (9)
SAD Cohorts 1 through 6
EXPERIMENTALParticipants 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.
SAD Cohorts 1 through 6 Placebo
PLACEBO COMPARATORParticipants will receive single doses of Matching Placebo of CORT125134 (capsule).
Food Effect Cohort 7
EXPERIMENTALParticipants 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.
Pharmacological Effect Cohort 8
EXPERIMENTALParticipants 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.
Proof of Concept (POC) Cohort 9
EXPERIMENTALParticipants 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.
MAD Cohorts 10 and 11
EXPERIMENTALParticipants 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.
MAD Cohorts 10 and 11 Placebo
PLACEBO COMPARATORParticipants will receive Matching Placebo of CORT125134 (capsule) up to a maximum frequency of twice a day for a total of 14 days.
MAD of PoPE Cohorts 12 and 13
EXPERIMENTALProof 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.
MAD of PoPE Cohort 12 and 13 Placebo
PLACEBO COMPARATORParticipants 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.
Interventions
Oral capsules
Placebo
Challenge agent
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Quotient Clinical
Nottingham, Nottinghamshire, NG11 6JS, United Kingdom
Related Publications (1)
Hunt H, Donaldson K, Strem M, Zann V, Leung P, Sweet S, Connor A, Combs D, Belanoff J. Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study. Clin Pharmacol Drug Dev. 2018 May;7(4):408-421. doi: 10.1002/cpdd.389. Epub 2017 Oct 2.
PMID: 28967708BACKGROUND
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Pui Leung
Quotient Clinical
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 21, 2017
First Posted
April 26, 2018
Study Start
September 1, 2014
Primary Completion
December 1, 2015
Study Completion
December 1, 2015
Last Updated
August 9, 2019
Record last verified: 2019-08