A study in healthy volunteers to investigate how the test medicine, zavacorilant, is taken up by the body when given in different dose levels, with food and without food
| ISRCTN | ISRCTN14072771 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14072771 |
| IRAS number | 1009209 |
| Secondary identifying numbers | CORT125329-142, IRAS 1009209 |
- Submission date
- 25/01/2024
- Registration date
- 21/03/2024
- Last edited
- 21/03/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
The Sponsor is developing the test medicine zavacorilant (also known 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.
This study will 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.
Who can participate?
Healthy men and women who are unable to have a baby, aged 18 to 60 years
What does the study involve?
Six volunteers will receive two 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 dose 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.
The researchers will collect blood and urine samples to complete safety tests and measure the amount of test medicine and one of its breakdown products (in blood).
What are the possible benefits and risks of participating?
Participants will get no medical benefit from taking part in this study. It is hoped that the development of a product to improve the treatment of neurodegenerative diseases such ALS, HD and AD will be of benefit to patients with these conditions.
Volunteers may experience side effects from the test medicine. Full information on possible side effects is in the Participant Information Sheet and Informed Consent Forms (PIS/ICFs). There is always a risk of unexpected side effects or an allergic reaction. To mitigate the risk, the researchers will ensure that volunteers meet the entry criteria for the study and monitor volunteers closely throughout the study.
Our screening tests might be of benefit if we find an important medical problem, but they might reveal something that the volunteer would prefer not to know about. If there are medically important findings in our tests at screening, or during the study, we will inform the volunteer’s GP.
Volunteers will be confined to the clinic during the study and must comply with the lifestyle restrictions described in the PIS-ICF, including periods of fasting from food and drink (except water) and short periods during which they’ll be allowed no fluids.
The test medicine might harm unborn children, so all volunteers must follow the restrictions on the donation of sperm or eggs and use acceptable contraception. Were a volunteer, or a partner of a volunteer to become pregnant during the study, the researchers would ask permission to follow up the pregnancy.
Volunteers will undergo many tests and procedures during the study. Blood sampling can cause soreness and bruising of the arms but these problems usually clear up within a few days to a few weeks. Susceptible volunteers may faint when we take blood samples; volunteers must lie down when we take blood samples to mitigate that risk. ECG stickers may cause local skin irritation.
Healthy volunteers will get no medical benefit from the test medicine; however, the aims of the study can be most efficiently met in volunteers with no concurrent medical conditions and who do not need to take concomitant medication that might interfere with the study objectives or increase the risk of the study. The risk/benefit evaluation in this study supports the use of healthy volunteers.
Volunteers will receive payment for participating in the study. There is always a risk that payment could represent coercion. However, payment will be based on committed time, inconvenience, travel and other expenses, not on risk. An ethics committee will review the payment to ensure that it is fair.
Where is the study run from?
Quotient Sciences Limited (UK)
When is the study starting and how long is it expected to run for?
January 2024 to June 2024
Who is funding the study?
Corcept Therapeutics (USA)
Who is the main contact?
Dr Sharan Sidhu, recruitment@weneedyou.co.uk
Contact information
Public, Scientific
149 Commonwealth Drive
Menlo Park
CA 94025
United States of America
| Phone | +1 (0)650 6882862 |
|---|---|
| hhunt@corcept.com |
Principal Investigator
Mere Way
Ruddington Fields
Nottingham
NG11 6JS
United Kingdom
| Phone | +44 (0)330 3031000 |
|---|---|
| recruitment@weneedyou.co.uk |
Study information
| Study design | Interventional single-centre open-labelled pharmacokinetic study including dose proportionality and food effect assessment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Part-randomized study |
| Study setting(s) | Pharmaceutical testing facility |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A Phase I pharmacokinetic assessment of zavacorilant softgel capsule formulation, including dose proportionality and food effect in healthy subjects |
| Study acronym | QSC301567 |
| Study objectives | 1. To determine the exposure of zavacorilant following administration of zavacorilant softgel capsules at increasing dose levels, including relative bioavailability in the fed and fasted states. 2. To assess the exposure of a zavacorilant metabolite following administration of the zavacorilant softgel capsules. 3. To provide additional safety and tolerability information for zavacorilant. |
| Ethics approval(s) |
Approved 08/03/2024, Health and Social Care Research Ethics Committee B (HSC REC B) (Unit 5, Lissue Industrial Estate West, Rathdown Walk, Moira Road, Lisburn, BT28 2RF, United Kingdom; +44 (0)28 9536 1400; recb@hscni.net), ref: 24/NI/0002 |
| Health condition(s) or problem(s) studied | Neurological diseases including amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD) and Alzheimer’s disease (AD) |
| Intervention | This is a part-randomized, uncontrolled trial. This three-cohort, healthy subject study aims to compare side effects and blood levels of the test medicine zavacorilant after being given with and without food (relative bioavailability), and at increasing dose levels. The study will take place at one non-NHS site and will consist of three cohorts of six healthy volunteers. In Cohort 1, subjects will be randomized to receive 250 mg zavacorilant once in the fed and once in the fasted state in a crossover manner over 2 periods. In Cohorts 2 and 3, subjects will receive up to 750 mg zavacorilant in either the fed or fasted state in a single period. For each period, subjects will be admitted to the clinical unit on the evening of Day -1, dosed in the clinical unit on Day 1 and discharged from the clinical unit on Day 4. For Cohort 1, there will be a minimum of 7 days between dosing occasions. Subject’s blood will be taken during the study for analysis of the test medicine and one of its breakdown products. The subject’s blood and urine will also be collected for safety testing. Subjects are expected to be involved in this study for approximately 6-7 weeks from screening to final discharge. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Relative bioavailability, food effect and tolerability |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Zavacorilant |
| Primary outcome measure | Pharmacokinetic (PK) parameters for zavacorilant measured using plasma samples, including but not limited to: Tmax, Cmax, AUC(0-last), AUC(0-inf), and T1/2, collected from days 1 to 4 at each period |
| Secondary outcome measures | 1. PK parameters for a zavacorilant metabolite measured using plasma samples, including but not limited to: Tmax, Cmax, AUC(0-last), AUC(0-inf), and T1/2, collected from days 1 to 4 at each period 2. Safety and tolerability evaluated by assessment of adverse events (AEs), vital signs, electrocardiograms (ECGs), physical examinations and laboratory safety tests from signing informed consent to the follow-up phone call |
| Overall study start date | 23/01/2024 |
| Completion date | 04/06/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 18 |
| Key inclusion criteria | Informed Consent and Compliance: 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study Demographics and Contraception: 3. Aged 18 to 60 years inclusive at the time of signing informed consent 4. Must agree to adhere to the contraception requirements defined in the Clinical Protocol Baseline Characteristics: 5. Healthy male subjects and healthy female subjects of non-childbearing potential according to the assessment of the Investigator, as based on a complete medical history including a physical examination, vital signs, 12-lead ECG, and clinical laboratory tests without any clinically significant abnormalities. 6. Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening 7. Weight 50-102 kg at screening |
| Key exclusion criteria | Medical/Surgical History and Mental Health: 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients 2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active. 3. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or GI disease, neurological or psychiatric disorder, as judged by the Investigator. Gilbert’s syndrome is not permitted. 4. Subjects with a history of cholecystectomy or gallstones Physical Examination: 5. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator or delegate at screening Diagnostic Assessments: 6. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the Investigator (laboratory parameters are listed in the protocol). Subjects with Gilbert’s Syndrome are allowed. 7. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 8. Evidence of renal impairment as indicated by: 8.1. An estimated glomerular filtration rate (eGFR) of <80 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) at screening 8.2. ALT and/or AST >1.5 times the upper limit of normal at screening 9. Female subjects of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative highly sensitive pregnancy test at screening and admission). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone [FSH] concentration ≥40 IU/L) 10. Clinically significant ECG abnormalities or vital sign abnormalities at screening or baseline (pre-first dose of IMP) including but not limited to: 10.1. QTcF > 450 msec based on a single ECG at screening and pre-(first) dose 10.2. Supine heart rate (HR) at rest of 40-100 bpm at screening and pre-(first) dose 10.3. BP outside the following ranges: diastolic BP 40-90 mmHg; systolic BP 90-140 mmHg at screening or before the first dose 10.4. ECGs and HR and BP can be retested twice in the supine position at intervals of approximately 5 minutes on a given day Prior Study Participation: 11. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer 12. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood Prior and Concomitant Medication: 13. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or vitamins/herbal remedies (other than up to 4 g of paracetamol per day) in the 14 days before the first IMP administration. Exceptions may apply, as determined by the Investigator and agreed by the Sponsor, if each of the following criteria are met: medication with a short half-life if the washout is such that no pharmacodynamic activity is expected by the time of dosing with IMP; the use of medication does not jeopardise the safety of the trial subject; and the use of medication is not considered to interfere with the objectives of the study. 14. Subjects who are currently using glucocorticoids or have a history of systemic glucocorticoid agonist use at any dose within the last 12 months or 3 months for inhaled products before the first dose of IMP. Subjects who have received up to two single doses of a glucocorticoid in another study more than 3 months before the first dose of study medication will not be excluded from taking part in the study. Lifestyle Characteristics: 15. History of any drug or alcohol abuse in the past 2 years 16. Regular alcohol consumption in male subjects >21 units per week and in female subjects >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) 17. A confirmed positive alcohol breath test at screening or admission 18. Current smokers and those who have smoked within the last 12 months 19. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months 20. A confirmed breath carbon monoxide reading of greater than 10 at screening or admission 21. Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in the protocol) at screening or admission Other: 22. Male subjects with pregnant or lactating partners 23. Subjects who are, or are immediate family members of, a study site or Sponsor employee 24. Failure to satisfy the Investigator of fitness to participate for any other reason |
| Date of first enrolment | 27/03/2024 |
| Date of final enrolment | 04/06/2024 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
Ruddington Fields
Nottingham
NG11 6JS
United Kingdom
Sponsor information
Industry
149 Commonwealth Drive
Menlo Park
CA 94025
United States of America
| Phone | +1 (0)650 6882862 |
|---|---|
| hhunt@corcept.com | |
| Website | http://www.corcept.com/ |
"ROR" |
https://ror.org/03ey3qt70 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 04/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Internal report 2. Submission to regulatory authorities The results of this Phase I healthy volunteer study are commercially very sensitive. It is not appropriate to share the results of this study with other researchers at this time. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
21/03/2024: ISRCTN received notification of combined HRA/MHRA approval for this trial on 21/03/2024.
25/01/2024: Study's existence confirmed by the HRA.
