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 CRN04894 (an adrenocorticotropic hormone [ACTH] receptor antagonist) in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome [EAS])

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:

1. Adult male or female, aged 18 years or more
2. Evidence of chronic 'active' ACTH-dependent Cushing's syndrome
3. Evidence of acutely 'active' ACTH-dependent Cushing's syndrome within 10 days of Day 1
4. 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:

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