A Multicenter, Phase 2/3, Dose Range Finding Study to Evaluate the Efficacy and Safety of Atumelnant in Adults with ACTH-Dependent Cushing’s Syndrome (ADCS) Including an Open-Label Extension for Long-Term Assessment. (EQUILIBRIUM-ADCS)

Ki vehet részt

• Part A and Part B Key Inclusion Criteria: 1. Male or female, ≥18 to <75 years of age at the time of signing the ICF. Participants≥16 years of age may be included at sites located in the US. Participants must have confirmed ADCS (pituitary, ectopic, or unknown source of excess ACTH after appropriate investigation) as evidenced by mUFC >1.3×ULN, confirmed by the central laboratory and available before Day 1 using adequate UFC samples as defined in the protocol
• Part C Key Inclusion Criteria: 1. Participants from Part A or Part B who complete the 12-week Treatment Periods on study drug or are rescued due to hypercortisolism and who, in the Investigator’s opinion, may benefit from participation in the OLE
• Part C Key Inclusion Criteria: 2. Late Screeners: When enrollment into Part B is closed, participants who were undergoing screening for Part B and who meet all Part B inclusion criteria may enroll directly into Part C. Participants may initiate Part C once all applicable eligibility criteria are confirmed
• Part A and Part B Key Inclusion Criteria: 2. Documentation of either abnormal dexamethasone suppression test and/or elevated late-night salivary cortisol levels performed historically, or pathologic confirmation of an ACTH-producing tumor
• Part A and Part B Key Inclusion Criteria: 3. Morning plasma ACTH >10 pg/mL
• Part A and Part B Key Inclusion Criteria: 4. Washout of any current drug therapy for ADCS following Screening Visit 1. The following minimum washout periods must be completed before baseline efficacy assessments are performed: • 2 weeks: Ketoconazole, levoketoconazole, or metyrapone. • 4 weeks: Osilodrostat, mifepristone, or cabergoline. • 8 weeks: Pasireotide LAR. Participants who complete the Washout Period and whose mUFC is not >1.3×ULNmay repeat one set of triplicate UFC collections, if deemed safe and clinically appropriate in the Investigator’s opinion

Ki nem vehet részt

• Part A and Part B Key Exclusion Criteria: 9. Participants who have previously taken atumelnant
• Part A and Part B Key Exclusion Criteria: 7. Participants who received pituitary radiation therapy within 3 years of screening
• Part A and Part B Key Exclusion Criteria: 10. Participants who will not benefit from chronic treatment with study drug or have a life expectancy of less than 6 months
• Part A and Part B Key Exclusion Criteria: 11. Clinically significant concomitant disease considered by the Investigator likely to affect safe participation in the study
• Part A and Part B Key Exclusion Criteria: 2. For medically untreated participants at Screening Visit 1, prior use of the following medications within the specified intervals prior to screening: - 2 weeks: Ketoconazole, levoketoconazole, or metyrapone. - 4 weeks: Osilodrostat, mifepristone, or cabergoline. - 8 weeks: Pasireotide LAR. Participants who have not completed the required washout periods are not eligible
• Part A and Part B Key Exclusion Criteria: 3. Use of any investigational drug within the past 60 days or 5 half-lives (whichever is longer) prior to the first dose; or plan to use an investigational drug in another study
• Part A and Part B Key Exclusion Criteria: 5. History of major surgery within 1 month prior to screening
• Part A and Part B Key Exclusion Criteria: 6. Pituitary surgery within 1 month of screening
• Part A and Part B Key Exclusion Criteria: 8. High-risk pituitary tumor pattern as defined by: - Current pituitary MRI findings of a lesion within 2 mm of the optic chiasm. - History of pituitary or ectopic tumor growth within 1 year after surgery(if performed) or radiation (unless it occurred during a period of medical therapy interruption) - Anticipated requirement for neurosurgical intervention or radiation therapy within the time course of the study. - Pituitary carcinoma
• Part A and Part B Key Exclusion Criteria: 1. Known history of, or concern for hypersensitivity reaction to atumelnant or any of its excipients
• Part A and Part B Key Exclusion Criteria: 4. Any history of mitotane use