An ADME Study of [14C]-CORT113176 in Healthy Male Subjects (QSC205084)
Research type
Research Study
Full title
An Open Label, Single-dose, Single-period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-CORT113176 in Healthy Male Subjects
IRAS ID
300250
Contact name
Sharan Sidhu
Contact email
Sponsor organisation
Corcept Therapeutics
Eudract number
2021-002544-78
Duration of Study in the UK
0 years, 1 months, 20 days
Research summary
Summary of research
The Sponsor is developing the test medicine, CORT113176, for the potential treatment of Amyotrophic Lateral Sclerosis (ALS). ALS is characterised by progressive degeneration of motor neurons in the brain and spinal cord, leading to muscle weakness and difficulty walking, speaking and swallowing.This study will aim to look at how the test medicine is taken up, broken down and removed by the body when given orally as capsules, in the fed state. To help investigate how this happens, the test medicine will be radiolabelled. ‘Radiolabelled’ means that the test medicine has a radioactive component, in this case Carbon-14 which is a type of naturally occurring radioactivity. The safety and tolerability of this test medicine will also be studied.
The study will consist of a single study period involving up to 6 healthy male volunteers, aged 30 - 65.
Volunteers will be admitted to the clinic the evening before the day of dosing. On Day 1, following an overnight fast of at least 10 hours, volunteers will receive a standard breakfast 30 minutes before they are given the test medicine. Volunteers will be given a single 450 mg dose of the radiolabelled test medicine as oral capsules.
Blood, urine and faecal samples will be collected throughout the study.
Volunteers will remain in the clinic up to Day 10, however if the relevant radioactivity elimination criteria have been met for all volunteers in the study before Day 10, they may be discharged early as a group. If the relevant radioactivity elimination criteria have not been met by Day 10, volunteers may be required to make up to 3 overnight return visits (each of 24 hours duration) for additional collection of urine and faecal samples.
Summary of Results
The Sponsor of this study was Corcept Therapeutics Incorporated, a small pharmaceutical company based in the US. The study was done by Quotient Sciences (a clinical research organisation) in Nottingham.The study took place from 23 Aug 2021 until 11 Oct 2021 at the Quotient Sciences’ clinical unit in Nottingham, UK.
We would like to take this opportunity to thank all study volunteers.What was this study about?
Corcept Therapeutics Incorporated (the Sponsor) is developing a new test medicine, currently named CORT113176, to treat Amyotrophic Lateral Sclerosis (ALS), which is also known as Motor Neurone Disease (MND). In patients with ALS, specific parts of the brain and spinal cord, called motor neurones, stop working properly. As motor neurones control important muscle activity, damage to these neurones can lead to muscle weakness, and difficulty with walking, speaking and swallowing. Patients with ALS may find that, as their condition develops, some or all of these activities become increasingly difficult and eventually these activities may become impossible.Patients with ALS have alterations in the normal daily levels of cortisol in the blood and saliva. Cortisol is a steroid hormone produced by the adrenal gland, which is known to affect the nervous system. The test medicine, CORT113176, reduces the effects of cortisol and has shown beneficial effects in a mouse model of ALS.
The aim of this study was to find out how the body takes up, breaks down and removes the test medicine when it is given by mouth to healthy men. This was done by ‘labelling’ the test medicine with a radioactive component (carbon-14; also referred to as 14C). 14C is a type of naturally occurring radioactivity that allows tracking of the test medicine to see how it is removed from the body. After volunteers had taken the labelled test medicine ([14C]-CORT113176), blood samples were taken from the volunteers at set times and measured for the levels of test medicine and radioactivity and all their urine and faeces (poo) were collected and tested for the levels of radioactivity.
This study also looked at the safety and tolerability of the test medicine.
Who took part in this study?
6 healthy men took part in the study. The youngest volunteer was 44 years old, and the oldest volunteer was 62 years old.How was this study done?
This was an open-label, single dose study. This means that all volunteers received one dose of test medicine and the volunteers and the study staff knew what medicine the volunteer was given.On Day 1, volunteers swallowed the radiolabelled test medicine, as 3 × 150 mg capsules (a total of 450 mg) with water.
Blood samples, urine and faeces (poo) were collected from the volunteers and analysed to find out how the body breaks down and removes the test medicine.
Volunteers stayed in the clinic until Day 10, then continued to collect all their urine and faeces (poo) at home. They brought their samples to the clinical unit each week until the tests showed that their body had removed the test medicine.
The study staff collected information about the volunteers’ health throughout the study.
What were the results of this study?
After the volunteers had taken the radiolabelled test medicine, most of the radioactivity (about 73%) was found in the faeces (poo). Some (about 16%) was found in the urine. These results mean that the liver does most of the processing and removal of the medicine from the body.There was more radioactivity in the blood than test medicine, which means that test medicine had likely been broken down into different parts or altered (metabolites) by the body. Further tests will be done on the blood samples to find out more about these metabolites.
The test medicine got into the bloodstream at about 15 minutes to 1 hour after it had been swallowed. The highest blood levels of test medicine occurred between about 1 and 3 hours after the test medicine was swallowed.
The test medicine was well tolerated in the 6 healthy male volunteers.
Did the volunteers have any unwanted effects?
Yes, 3 volunteers had unwanted effects. However, these unwanted effects were all mild and were not thought to be caused by the test medicine.Where can I find more information about this study?
For more information about the study, go to https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7C98ba9b33bc9247c9493808da874086bd%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637971008452103168%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=JUzU24SU36ligz7%2BQAjuOcYVEPVg81Tvx4uPUuwz%2FN8%3D&reserved=0 and search for the NCT number NCT04990310.Are there additional studies?
The Sponsor will continue to develop CORT113176 for the treatment of patients suffering from ALS.REC name
London - Riverside Research Ethics Committee
REC reference
21/LO/0512
Date of REC Opinion
29 Jul 2021
REC opinion
Further Information Favourable Opinion