Antipsychotic-induced weight gain (AIWG) Nutritional, Metabolic, Endocrine
Conditions
Interventions
This is a randomised, double blind, placebo-controlled trial. This one-part, healthy subject proof of concept study aims to assess whether the test medicine, miricorilant, dosed with food, reduces the
Sponsors
Corcept Therapeutics Incorporated (USA)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent 2. Willing and able to communicate and participate in the whole study 3. Male 4. Aged 18 to 55 years inclusive at the time of signing informed consent 5. Agree to adhere to the contraception requirements defined in the Clinical Protocol 6. Healthy as determined by medical evaluation including medical history, physical examination, vital signs, 12-lead ECG, clinical laboratory profiles (haematology, clinical chemistry and urinalysis), as deemed by the Investigator or designee 7. BMI of 18.0 to 25.0 kg/m² as measured at screening 8. Stable body weight as indicated by assessment at screening and pre-dose Day 1. Pre dose Day 1 body weight to be within ±2.0% of screening body weight (measured in the morning following a minimum 8 hour fast)
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients (including lactose) 2. Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator. Subjects with inactive seasonal hay fever may be included 3. H istory of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease (including cholecystectomy and gall stones ), neurological or psychiatric disorder, as judged by the Investigator 4. Subject has a condition that could be aggravated by glucocorticoid and/or mineralocorticoid antagonism (e.g. asthma, any chronic inflammatory condition, postural hypotension/orthostatic symptoms). Subjects with childhood (aged less than 18 years) asthma may be included provided they have had no symptoms and required no treatment for at least 5 years 5. History of additional risk factors for torsades de pointes (e.g. heart failure, hypokalaemia, family history of long QT syndrome) 6. Lack of suitable veins for multiple venepunctures/cannulation as assessed by the Investigator or delegate at screening 7. Clinically significant abnormal clinical chemistry (including ALT, AST and/or bilirubin more than the ULN at screening), haematology or urinalysis as judged by the Investigator 8. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 9. Subject has renal impairment as evidenced by an estimated glomerular filtration rate (eGFR) of 450 msec 10.2. Supine heart rate (HR) at rest of >100 bpm 10.3. Blood pressure (BP) outside the following ranges: diastolic BP 40-90 mmHg; systolic BP 90-140 mmHg (subjects aged 18-45 years) and 90-160 mmHg (subjects aged >45 years) 10.4. HR and BP can be retested twice in the supine position at intervals of approximately 5 minutes on a given day 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. Subjects who have received miricorilant in study QSC300704 in the 6 months prior to the first dose of miricorilant in this study 13. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood 14. 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 IMP administration. COVID-19 vaccines are accepted concomitant medications 15. Subjects who are currently using glucocorticoids or have a history of systemic glucocorticoid use at any dose within the last 12 months or 3 months for inhaled glucocorticoids. Subjects who have received up to two single doses of a glucocorticoid in another study more than 3 months before first dose of study medication will not be excluded from taking part in the study 16. Any contraindication to the use of olanzapine as per the SmPC 17. History of any drug or alcohol abuse in the past 2 years 18. Regular alcohol consumption >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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in body weight evaluated by analysis of body weight measurements taken from Day 1 and Day 22. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change in body weight evaluated by analysis of body weight measurements taken from Day 1 and Days 8 and 15. 2. PK parameters for miricorilant and its metabolite, CORT118335-P9, as applicable, evaluated by analysis of blood samples collected from Day 1 to Day 22. 3. Changes in plasma or serum concentrations of glucose, insulin, triglyceride and cholesterol and HOMA-IR from baseline evaluated by analysis of blood samples collected from Day 1 and Days 8, 15 and 22. 4. Changes in waist-to-hip ratio compared to baseline evaluated by analysis of waist-to-hip ratio measurements taken on Day 1 and Days 8, 15 and 22. 5. Safety, evaluated by monitoring adverse events (AEs) from signing the informed consent form until the follow-up visit (prior to Day -1 until Day 35±2) and results from safety tests, ECGs, vital signs measurements and physical examinations at screening, and at intervals from pre-dose on Day 1 to Day 22 and on Day 35±2. 6. Incidence and degree of increases in hepatic aminotransferases compared to baseline evaluated by analysis of blood samples collected from Day 1 to Day 22. | — |
Countries
United Kingdom
Outcome results
None listed