Single and Multiple Ascending Dose Study of CORT125329 (QSC203060)
Research type
Research Study
Full title
A Phase 1 Adaptive Dose, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered CORT125329 in Healthy Subjects, with an Optional Pharmacological Effects Cohort
IRAS ID
282265
Contact name
Hazel Hunt
Contact email
Sponsor organisation
Corcept Therapeutics
Eudract number
2020-001741-38
Duration of Study in the UK
0 years, 7 months, 12 days
Research summary
Summary of Research
The Sponsor is developing the test medicine, CORT125329, for the potential treatment of antipsychotic-induced weight gain (AIWG). AIWG is the condition in which patients taking antipsychotic medications have a tendency to gain weight. In addition, antipsychotic medications can increase the risk of patients developing cardiovascular disease (diseases of the heart/blood vessels).
The study will try to identify the safety and tolerability of single (Part 1) and multiple (Part 2) ascending doses of the test medicine. It will also try to identify how the test medicine is taken up by the body (pharmacokinetics). Optional Part 3 may assess what the test medicine does to the body (pharmacodynamic effect).
The study will consist of up to 3 parts, involving up to 132 healthy male and female [of non-childbearing potential] volunteers.
In Part 1, up to 80 volunteers in up to 8 cohorts will receive a single dose of the test medicine or matching placebo. Volunteers will remain in clinic until 72-hours post-dose. They will return 96-hours post-dose for a final PK sample. A follow-up visit will take place on approximately Day 11.
In Part 2, up to 40 volunteers in up to 4 cohorts will receive multiple doses of the test medicine or matching placebo for 14 days. Volunteers will remain in clinic until 48-hours post-final dose. They will return 72-hours and 96-hours post-final dose for PK samples and safety assessments. A follow-up visit will take place approximately 9 days post-final dose.
Part 3 consists of two periods of up to 12 volunteers in a single cohort, volunteers will receive a single dose of a marketed medicine (prednisone) in Period 1 and prednisone plus a single dose of the test medicine in Period 2. Volunteers will remain in clinic until 24-hours post-dose for period 1 and until 72-hours post-dose for period 2. A follow-up visit will take place on approximately Day 11.
Summary of Results
Study title: A three part study in healthy male and female volunteers to look at the safety and tolerability of the test medicine CORT125329 and how it is taken up by the body when given as single and multiple doses
(A Phase 1 Adaptive Dose, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered CORT125329 in Healthy Subjects, with Optional Pharmacological Effects Cohorts)
This is a summary of results from the above Phase 1 clinical study in healthy volunteers.
The Sponsor of this study was Corcept Therapeutics, a small pharmaceutical company based in the US. The study was done by Quotient Sciences (a clinical research organisation) in Nottingham, UK.
The study took place from 23 Oct 2020 until 17 Jan 2022 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 (the Sponsor) is developing a new test medicine, CORT125329. It is hoped this medicine will reduce the weight gain caused by antipsychotic medicines such as olanzapine, clozapine and risperidone. Antipsychotic medications are mainly given to patients to treat different mental illnesses such as schizophrenia and bipolar disorder.
Antipsychotic-induced weight gain (AIWG) is the condition in which patients taking antipsychotic medications have a tendency to gain weight. In addition to weight gain, antipsychotic medications increase insulin resistance (this can lead to high blood sugar levels) and cholesterol and serum triglycerides (types of fat in the blood), thereby increasing the risk of patients developing cardiovascular disease (diseases that affect the heart and blood vessels).
There were 3 parts to this study. Different volunteers participated in each part.
Part 1 was the first time the test medicine had been given to humans. It investigated the safety and tolerability of the test medicine in 63 healthy volunteers when given as one dose fasted (without food) or with food. This study also looked at how the test medicine was taken up by the body.
Part 2 investigated the safety and tolerability of multiple doses of the test medicine given every day for 14 days in 32 healthy volunteers given either fasted (without food) or after food. One of the possible effects of the test medicine is to increase blood levels of 2 hormones, called ACTH and cortisol, so blood levels of those hormones were measured. This study also looked at how the test medicine was taken up by the body.
Part 3 investigated the effects of the test medicine when given at the same time as a licensed medicine called prednisone. Prednisone is a corticosteroid (a medication used to reduce inflammation and supress the immune system) which is marketed in Germany and the United States of America. Part 3 of the study was designed to find out whether the test medicine can prevent some of the effects of prednisone, in 20 healthy volunteers, given with food. Safety and tolerability were also assessed.
Who took part in this study?
In Part 1, 63 healthy men and women took part. The youngest volunteer was 20 years old, and the oldest volunteer was 59 years old.
In Part 2, 32 healthy men and women took part. The youngest volunteer was 24 years old, and the oldest volunteer was 57 years old.
In Part 3, 20 healthy men and women took part. The youngest volunteer was 25 years old, and the oldest volunteer was 60 years old.
How was this study done?
In both Parts 1 and 2, volunteers were dosed in small groups, one after the other, starting with a low dose. For each group, the dose was increased or the recipe of the capsules was changed depending on results from the previous group.
Some volunteers in each group in Parts 1 and 2 took a placebo or “dummy test medicine”, which looked like the test medicine but contained no active ingredients. Whether a volunteer received the test medicine or placebo was decided at random.
Parts 1 and 2 were double-blind, which means that volunteers did not know whether they received test medicine or placebo and the study staff did not know either. Blinding the study means that the results were not affected by volunteers or study staff knowing whether the test medicine or placebo had been taken.
Part 3 was open-label. This means that the volunteers knew which treatment they were receiving. Volunteers in Part 3 received the test medicine and prednisone.
In all 3 study parts, blood samples were collected from the volunteers throughout and analysed to find out the amount of test medicine in the body. The study staff also collected information about the volunteers’ health throughout all 3 parts of the study.
Part 1
Volunteers were dosed in 8 groups of 7 or 8 people. Four groups took the test medicine on an empty stomach and four groups took it after food, to see if food made any difference to the way the body processed the test medicine.
Each volunteer in Part 1 took a single dose of test medicine or placebo, by mouth, with water. Volunteers went home on Day 4, then came back on Days 5 and 11 for blood samples and safety checks.
Each group took a different dose or recipe of the capsule, or differed in whether the test medicine was taken with or without food. The doses and recipes were decided based on results from the previous groups. The highest dose tested was 1200 mg.Part 2
Volunteers were dosed in 4 groups of 8 people. Three groups took the test medicine on an empty stomach and 1 group took it after food, to see if food made any difference to the way the body processed the test medicine.
Each volunteer in Part 2 took daily doses of test medicine or placebo, by mouth, with water for 14 days. Volunteers went home on Day 16, then came back on Days 17, 18 and 23 for blood samples and safety checks.
The daily doses tested in Part 2 ranged from 100 mg to 900 mg and were decided based on the results from Part 1 and earlier groups in Part 2.Part 3
In Part 3, volunteers were split into 2 groups. For Group A, volunteers received the same treatments in the same order. For Group B, volunteers received the same treatments but in a different order and the order was decided at random. Both groups had the test medicine after food.
Volunteers in both groups went to the clinical unit for 2 study visits.
For Group A Study Visit 1, volunteers received 20 mg of prednisone as a tablet to swallow with water on Day 1 and went home on Day 2. There was then a break of at least 7 days before Study Visit 2 so that the treatment was cleared from the body. Then, for Study Visit 2, volunteers received 20 mg of prednisone as a tablet along with 1200 mg of the test medicine as capsules to swallow with water on Day 1 and went home on Day 4. The volunteers then returned on Days 5 and 11 for blood samples and safety checks.
For Group B, volunteers received 20 mg of prednisone as a tablet to swallow with water on Day 1 in one visit and, in the other visit, received 20 mg of prednisone as a tablet along with 600 mg of the test medicine as capsules to swallow with water on Day 1. The volunteers went home on Day 2 of each visit. There was a break of at least 10 days between the first and second study visits so that the treatment was cleared from the body. The volunteers then returned on Days 5 and 11 for blood samples and safety checks.
The results after taking prednisone alone were compared with the results after prednisone was given alongside the test medicine to see if there were any different effects on the body.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 and the amount of test medicine in the blood went up by a similar degree to the dose (dose proportionality).
The amount of test medicine in the blood was higher when it was taken after a meal.When the test medicine was taken daily for 14 days, blood levels of test medicine went up over the first 7 days, then stayed at the same level until the volunteers stopped taking it.
The amounts of test medicine in the blood were similar for the 2 different recipes of the capsules tested.
When the test medicine was given daily for 14 days, the amounts of 2 hormones measured in the blood were similar compared with placebo (the “dummy test medicine”).When the test medicine was taken with prednisone, it prevented some of the effects of prednisone. The higher dose of test medicine prevented these effects more.
The test medicine was well tolerated in the healthy volunteers.Did the volunteers have any unwanted effects?
Yes.
In Part 1, unwanted effects occurred in 12 out of the 47 volunteers who took a single dose of the test medicine and in 1 out of the 16 volunteers who took placebo. 6 of these volunteers had unwanted effects that may have been caused by the test medicine, all of which were mild.In Part 2, unwanted effects occurred in 13 out of the 24 volunteers who took repeated doses of the test medicine. In 6 of these volunteers, the unwanted effects may have been caused by the test medicine. Unwanted effects occurred in 5 out of the 8 volunteers who took placebo. In 5 of these volunteers, the unwanted effects may have been caused by the placebo. All the unwanted effects were mild.
In Part 3, unwanted effects occurred in 7 out of 20 volunteers after prednisone alone and in 2 out of 18 volunteers after prednisone together with test medicine. 1 of these volunteers had unwanted effects that may have been caused by the prednisone and test medicine taken together. 1 volunteer had an unwanted effect after taking prednisone alone, that was moderate. All the other unwanted effects were mild.
Overall, the most common unwanted effects thought to be caused by the test medicine were fatigue (tiredness), abdominal pain (tummy ache) and gastro-oesophageal reflux disease (indigestion).
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%7C8832e0e3e0384d883d5e08dae4e15fa5%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638073953866355112%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=iKM0bsOLvH3ySPnFreIdPILVsn7boCe%2BZeA1hM1jSes%3D&reserved=0 and search for the NCT number NCT04672512.
Are there additional studies?
The Sponsor will continue to develop CORT125329 as a treatment to reduce the weight gain caused by antipsychotic medicines.
REC name
Wales REC 2
REC reference
20/WA/0185
Date of REC Opinion
16 Jul 2020
REC opinion
Favourable Opinion