Single and Multiple Ascending Dose Study of CORT125236 (QSC203061)
Research type
Research Study
Full 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 A Pharmacological Effects Cohort
IRAS ID
297712
Contact name
Hazel Hunt
Contact email
Sponsor organisation
Corcept Therapeutics
Eudract number
2021-001407-32
Duration of Study in the UK
0 years, 7 months, 28 days
Research summary
Research Summary
The Sponsor is developing the test medicine, CORT125236, for the potential treatment of Cushing’s syndrome, a condition which is caused by having too much of a hormone called cortisol in the body.
This is a 3-part, single-center, first-in-human study of single ascending doses (Part 1) and multiple ascending doses (Part 2) of the test medicine, CORT125236, in healthy male and female (non-childbearing) subjects. Optional Part 3 will investigate the effects of the test medicine when given at the same time as a licensed medicine called prednisone.
In Part 1, up to 48 volunteers (split into 6 cohorts of 8) will receive a single dose of the test medicine or matching placebo on Day 1. The dose given to each cohort will be based on safety, tolerability data and pharmacokinetic (PK) data of previous cohorts. As a safety precaution, sentinel dosing will be implemented for each cohort (2:1 test medicine:placebo). Volunteers will be discharged on Day 4 and will return on Day 5 for further assessments.
In Part 2, up to 32 volunteers (up to 4 cohorts of 8) will receive multiple doses of the test medicine or matching placebo up to twice a day for 14 days. Sentinel dosing will be implemented if required based on preceding safety and PK data. Each group may receive a different dose of the test medicine, dependent on data from previous cohorts. Volunteers will be discharged on Day 16 and return on Day 17 for further assessments.
Optional Part 3 involves two study visits. Volunteers will receive a single dose of prednisone in Period 1 and prednisone plus a single dose of the test medicine in Period 2. Volunteers will be discharged on Day 2 (Period 1) and Day 4 (Period 2).
For all groups, volunteers will return for a follow-up visit approximately 9 days post-final dose.
Summary of Results
This study was sponsored by Corcept Therapeutics Incorporated and conducted by Quotient Sciences (a clinical research organisation) at its clinical unit in Nottingham, UK.
The study took place from 25 Aug 2021 until 03 Feb 2023.
We would like to take this opportunity to thank all study volunteers.
What was this study about?
The aim of this study was to find out how single and multiple doses of the test medicine, CORT125236, were taken up by the body and how they were tolerated. Single doses were also given with food and without food, to see if food made any difference to the way the body took up the test medicine. The study also looked at the effects of the test medicine on 2 hormones and whether the test medicine could prevent some of the effects of another approved medicine called prednisone.This was the first time the test medicine had been given to people.
Who took part in this study?
There were 3 parts to the study, with different volunteers in each part.
Volunteers were healthy men and healthy women who were unable to have children.
Part 1 had 48 volunteers 20 to 60 years old, Part 2 had 24 volunteers 25 to 60 years old, and Part 3 had 10 volunteers 34 to 59 years old.How was this study done?
In Parts 1 and 2, some volunteers in each group took a placebo or “dummy test medicine”, which looked like the test medicine but contained no active ingredient. Whether a volunteer received the test medicine or placebo was decided at random. Parts 1 and 2 were also double-blind, which means that volunteers did not know whether they received test medicine or placebo and the study staff did not know either. This means that the results were not affected by volunteers or study staff knowing whether the test medicine or placebo had been taken.In Part 1, volunteers were dosed in 6 small groups, one after the other, starting with a low dose. Each volunteer in 5 of the groups took one dose of test medicine or placebo, on an empty stomach. The other group took the test medicine or placebo after eating. Between each group, the dose was increased, except for the fed group.
In Part 2, volunteers were dosed in 3 small groups, one after the other. Each volunteer took the test medicine or placebo once a day, on an empty stomach, for 14 days. Between each group, the dose was increased.
In Part 3, volunteers took a single dose of prednisone on one day, followed at least 7 days later by another single dose of prednisone together with the test medicine. Doses were given on an empty stomach.
For all 3 parts, doses were given by mouth with water.
For all 3 parts of the study, blood samples were collected after the volunteers were dosed with the test medicine to find out the amount of test medicine in the body over time. Volunteers went home and came back for blood samples and safety checks. In Part 3, additional blood samples were collected to measure biomarkers (biomarkers indicate processes that are happening in the body) to find out if the test medicine can prevent some of the effects of prednisone.What were the results of this study?
Volunteers who took higher doses of the test medicine had higher amounts of test medicine in the blood.The amount of test medicine in the blood was lower when it was taken after a meal.
When the test medicine was taken daily for 14 days, blood levels of test medicine on Day 7 were the same as on Day 14.
When the test medicine was taken with prednisone, it prevented most of the effects of prednisone.
The test medicine was well tolerated in the healthy volunteers.
Did the participants have any unwanted effects?
YesIn Part 1, unwanted effects occurred in 7 out of the 36 volunteers who took the test medicine but none of these were caused by the test medicine. Unwanted effects occurred in 5 out of the 12 volunteers who took placebo and 3 of these volunteers had unwanted effects that may have been caused by the placebo.
In Part 2, unwanted effects occurred in 13 out of the 18 volunteers who took the test medicine and 5 of these volunteers had unwanted effects that may have been caused by the test medicine. Unwanted effects occurred in 4 out of the 6 volunteers who took placebo and 1 of these volunteers had an unwanted effect that may have been caused by the placebo.
In Part 3, unwanted effects occurred in 3 out of the 10 volunteers who took prednisone on its own and 1 of these volunteers had an unwanted effect that may have been caused by it. An unwanted effect occurred in 1 volunteer after taking prednisone and the test medicine together, but this was not caused by the test medicine.All the unwanted effects were mild.
Overall, the most common unwanted effect thought to be caused by the test medicine was ear infection.
REC name
HSC REC A
REC reference
21/NI/0103
Date of REC Opinion
2 Jul 2021
REC opinion
Favourable Opinion