PK Study of Zavacorilant in Healthy Volunteers (QSC301567)
Research type
Research Study
Full title
A Phase I Pharmacokinetic Assessment of Zavacorilant Softgel Capsule Formulation, Including Dose Proportionality and Food Effect in Healthy Subjects
IRAS ID
1009209
Contact name
Hazel Hunt
Contact email
Sponsor organisation
Corcept Therapeutics Incorporated
ISRCTN Number
ISRCTN14072771
Research summary
Research Summary
The Sponsor is developing the test medicine zavacorilant (also know as CORT125329), for the potential treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS - also known as Motor Neurone Disease), Huntington’s disease (HD), and Alzheimer’s disease (AD). Neurodegenerative diseases occur when nerve cells in the brain, spinal cord or body lose function over time and ultimately die. These diseases affect millions of people worldwide. It’s common for patients to have a higher level of cortisol (a steroid hormone produced by the adrenal gland), which is known to affect the nervous system. The test medicine reduces the effects of cortisol and has shown beneficial effects in a mouse model of ALS.
In this study, we’ll compare side effects and blood levels in healthy volunteers after the test medicine is given with and without food (relative bioavailability) and at increasing dose levels.
This study will take place at 1 site in Nottingham.
We plan to enrol 18 healthy men and women who are unable to have a baby, aged 18 to 60 years.
Six volunteers will receive 2 single doses of test medicine as capsules, one fasted and one fed. They’ll stay in the clinic for up to 4 nights each dose, and take up to 7 weeks to finish the study.
Twelve volunteers will receive a single doses of test medicine as capsules, either fasted or fed. They’ll stay in the clinic for up to 4 nights, and take up to 6 weeks to finish the study.
We’ll collect blood and urine samples to complete safety tests and measure the amount of test medicine and one of it's breakdown products (in blood).Summary of Results
The Sponsor for this study was Corcept Therapeutics Incorporated and the study was conducted by Quotient Sciences (a clinical research organisation) at their clinical unit in Nottingham, UK.
The study took place from 28 Mar 2024 until 31 May 2024.
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 the test medicine (zavacorilant), given as softgel capsules, was absorbed by the body when given in a fed state (with food) and fasted state (without food), and at different dose levels. A metabolite of the test medicine (a product formed when the test medicine is broken down by the body) was also measured.The test medicine in softgel capsules is a new formulation and is different from the formulation tested in previous trials. It was planned that 3 groups of volunteers would be dosed in this study. The results from the first 2 groups showed that not as much test medicine was absorbed into the body as expected, so it was decided to stop the study and the 3rd group was not dosed.
Who took part in this study?
12 healthy volunteers (healthy men and healthy women who were not able to have children) took part in the study (6 volunteers in each group). The youngest volunteer was 26 years old and the oldest volunteer was 59 years old.How was this study done?
The study was open labelled. This means that the volunteers knew which treatment they were receiving.All doses of test medicine were taken by mouth, with water.
Group 1 was dosed once with food and once without food, to see if food made any difference to the amount of the test medicine absorbed into the body. The order in which each volunteer was dosed was decided at random – half of the volunteers were dosed with food on Day 1 in the first period and without food on Day 1 in the second period, and the remaining volunteers were dosed the other way around. The same amount of test medicine was given each time. There was a break of at least 7 days between each dose so that the first dose of test medicine was cleared from the body before volunteers were given the next dose. Volunteers went home on Day 4 in each period. In the second period, volunteers came back on Day 12 for safety checks.
Based on the results from Group 1, it was decided to dose Group 2 with food.
Group 2 received a higher dose of test medicine than Group 1 once, with food, on Day 1. Volunteers went home on Day 4 and came back on Day 12 for safety checks.
Blood samples were collected whilst the volunteers were in the clinic to find out the amount of test medicine in the body over time. The study staff also collected information about the volunteers’ health throughout the study.
What were the results of this study?
In Group 1, the amounts of test medicine and metabolite in the blood were higher when test medicine was taken with food than when taken without food.In Group 2, there were higher amounts of test medicine in the blood compared with Group 1, and the amount of test medicine in the blood went up by a similar degree to the dose.
In this study, the new test medicine formulation (softgel capsule) led to a lower amount of test medicine in the blood compared with previous studies which used similar doses of test medicine with a different formulation (hardgel capsule).
The test medicine was well tolerated in the healthy volunteers.
Did the participants have any unwanted effects?
Yes.Unwanted effects occurred in 3 out of the 12 volunteers who took the test medicine.
Two of the unwanted effects were mild. The other unwanted effect (lower than normal levels of neutrophils, a type of white blood cell) was severe. The volunteer came back to the clinic for extra visits, and extra safety tests were performed.
None of the unwanted effects were caused by the test medicine.
Where can I find more information about this study?
For more information about the study, go to www.isrctn.com and search for the ISRCTN number: ISRCTN14072771.REC name
HSC REC B
REC reference
24/NI/0002
Date of REC Opinion
8 Mar 2024
REC opinion
Further Information Favourable Opinion