Single and Multiple Ascending Dose Study of CORT125329 in Healthy Participants

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

The purpose of this study is to evaluate the dose-related safety, tolerability, pharmacokinetics (PK) and pharmacological effects (PD) of CORT125329 after single and multiple ascending oral doses of CORT125329 lipid capsule formulations in healthy participants.

This is a 3-part, single-center study of single and multiple ascending doses of CORT125329 in healthy participants.

Part 1 will be a double-blind, randomized, placebo-controlled assessment of single ascending doses (SAD) of CORT125329 lipid capsule formulations. Participants will be enrolled sequentially into 1 of up to 8 cohorts, each containing 8 participants.

Part 2 will be double-blind, randomized, placebo-controlled assessments of multiple oral ascending doses (MAD) of CORT125329 lipid capsule formulations. Participants will be enrolled sequentially into 1 of up to 4 cohorts, each containing 8 participants.

Optional Part 3 will be an open-label, 2-way fixed sequence cross-over study and will serve as proof of PD (glucocorticoid receptor modulation) for CORT125329 lipid capsule formulations. Participants will be enrolled in a single cohort of 10 participants.

Throughout the study, routine safety tests will be performed. In selected parts of the study, assessments of PK (CORT125329), changes in serum cortisol and plasma adrenocorticotrophic hormone (ACTH), and changes in hematological and bone biomarkers will be measured.

Inclusion Criteria:

• Body mass index of 18.0 to 30.0 kg/m^2
• Weight of ≤102 kg
• Must agree to adhere to the contraception requirements
• Additional criteria apply.

Exclusion Criteria:

• Received any investigational medicinal product in a clinical research study within the 90 days
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption
• Current smokers and those who have smoked within the last 6 months
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 6 months
• Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative pregnancy test at screening and admission)
• Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the Investigator
• Confirmed positive drugs of abuse test result
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
• Active renal and/or hepatic disease
• History of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, GI, neurological or psychiatric disorder, as judged by the Investigator
• Any form of cancer within the last 5 years (exceptions apply)
• History and/or symptoms of adrenal insufficiency
• History of clinically significant gastrointestinal disease
• Has a condition that could be aggravated by glucocorticoid antagonism
• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
• Presence or history of clinically significant allergy requiring treatment
• Donation or loss of greater than 400 mL of blood or plasma within the previous 3 months
• Are taking, or have taken, any prescribed, over-the-counter drug (other than 4 g per day paracetamol), vitamins or herbal remedies within 14 days before the study (exceptions may apply on a case by case basis)
• 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 products
• Additional criteria apply.