A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing's Syndrome

This is a Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with atumelnant (also known as CRN04894) (an adrenocorticotropic hormone [ACTH] receptor antagonist) over a 10-day or 14-day treatment period in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome [EAS]). Participants will receive oral atumelnant once daily for 10 days followed by monitoring during 4 'wash-out' days, or for 14 days.

Inclusion criteria

• Adult male or female, aged 18 years or more
• Evidence of chronic 'active' ACTH-dependent Cushing's syndrome
• Evidence of acutely 'active' ACTH-dependent Cushing's syndrome within 10 days of Day 1
• Participants with documented ACTH-dependent Cushing's syndrome taking short-acting steroidogenesis inhibitors (ketoconazole, levoketoconazole, osilodrostat, or metyrapone) may participate after a washout period of at least 5 days, if they meet other study inclusion criteria, relative to Investigator's judgment. Participants with documented ACTH-dependent Cushing's syndrome taking cabergoline may participate after a washout period of at least 14 days, if they meet other study inclusion criteria

Exclusion criteria

• Women who are pregnant or lactating
• History of bilateral adrenalectomy
• Previous pituitary MRI findings of a putative ACTH-secreting lesion within 3 mm of the optic chiasm
• Presence of any known malignancy
• Use of mitotane
• Previous unsuccessful surgery for Cushing's syndrome within 6 weeks