Impact of 1 mg Osilodrostat Therapy on Mild Autonomous Cortisol Secretion (MACS)

NCT07104812 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 25-007009
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of 1 mg osilodrostat therapy in patients with mild autonomous cortisol secretion (MACS), and to determine the impact on 24h urine steroid metabolome and circadian cortisol/cortisone concentrations

Conditions

Mild Autonomous Cortisol Secretion; Autonomous Cortisol Secretion (ACS)

Keywords

hypercortisolism; cortisol excess; Adrenal adenoma; Adrenal hyperplasia; Cushing Syndrome

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  Number of adverse events

  4 weeks

• Adrenal insufficiency

  Number of subjects to experience adrenal insufficiency, defined as combined measurements of cortisol \< 7 mcg/dL and ACTH\>60 pg/dL or single cortisol \< 5 mcg/dL

  4 weeks

Study Arms (1)

Mild autonomous cortisol secretion (MACS)

EXPERIMENTAL

Women and men diagnosed with MACS who are patients at Mayo Clinic.

Drug: Osilodrostat 1 MG

Interventions

Osilodrostat 1 MG DRUG

Osilodrostat 1 mg administered between noon and 6 pm daily, for 4 weeks

Mild autonomous cortisol secretion (MACS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Age ≥ 18 years
• Diagnosed with MACS
• At least 2 abnormal post-dexamethasone cortisol results:
• i. 1 mg post-dexamethasone cortisol \>1.8 mcg/dL or ii. 8 mg post-dexamethasone cortisol \>1 mcg/dL
• Historical dexamethasone suppression test results can be used if performed within 24 months prior to enrollment.
• Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia)
• At least one of the following comorbidities:
• Obesity (BMI\>30 kg/m2)
• Dysglycemia
• Dyslipidemia
• Hypertension
• Osteopenia
• Osteoporosis

You may not qualify if:

• Planned alternative therapy for MACS during the study period
• Current use of oral exogenous glucocorticoid therapy
• Current use of opioid therapy \>20 MME/day
• Planned use of oral exogenous glucocorticoid therapy
• Planned use of opioid therapy \>20 MME/day
• Use of injectable glucocorticoid within the last 6 weeks or anticipated glucocorticoid use during the study period.
• Hypokalemia of hypomagnesemia at baseline visit
• Prolonged QTc on baseline ECG
• Concomitant therapy with medications likely to lead to drug-drug interactions (based on PI review).
• Investigator's judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia

Sponsors & Collaborators

• Mayo Clinic: lead
• RECORDATI GROUP: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

MeSH Terms

Conditions

Cushing Syndrome; ACTH Syndrome, Ectopic; Adrenal Hyperplasia, Congenital

Interventions

Osilodrostat

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Neoplasms; Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Gonadal Disorders

Study Officials

• Irina Bancos, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: August 5, 2025
• Study Start: January 14, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)