A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement

NCT06430528 | Recruiting FDA Drug

• 1 other identifier: HUM00246263
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The major goal of this study is to determine the incidence of adrenal insufficiency in patients with endogenous Cushing syndrome receiving osilodrostat treatment combined with a replacement of glucocorticoid (block-and-replace approach). The investigators are also evaluating new biomarker steroids to reflect adequate osilodrostat dosing, the durability and safety, and clinical improvement during treatment.

Conditions

Endogenous Cushing Syndrome; Adrenal Insufficiency; Hypercortisolism

Keywords

Osilodrostat; Glucocorticoid; Methylprednisolone; Medrol

Outcome Measures

Primary Outcomes (1)

• Percent of participants who experience an adrenal insufficiency event during Phase 1 (titration phase)

  based on evidence of hypotension (systolic BP \<90 mmHg) and/or hypoglycemia (glucose \<45 mg/dL) with antecedent symptoms (examples: anorexia, nausea, abdominal pain, orthostasis) and with a resolution of signs upon receiving rescue glucocorticoid therapy

  Through phase 1, approximately 24 weeks

Secondary Outcomes (11)

• Correlation between AM cortisol and 11OHA4 measurements

  Up to end of study, approximately 48 weeks

• Rate of adrenal insufficient episodes per patient per year

  Up to end of phase 2 (approximately 48 weeks)

• Frequency of cortisol withdrawal symptoms

  Up to end of phase 2 (approximately 48 weeks)

• Change in weight

  Baseline, end of phase 2 (approximately 48 weeks)

• Change in diastolic blood pressure

  Baseline, end of phase 2 (approximately 48 weeks)

Study Arms (1)

Observational cohort

Participants with Cushing syndrome consented to participate in block-and-replace osilodrostat therapy.

Drug: Osilodrostat

Interventions

Osilodrostat DRUG

Add methylprednisolone to osilodrostat therapy after first dose and continue during osilodrostat titration.

Also known as: Isturisa

Observational cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients receiving care at the University of Michigan.

You may qualify if:

• Endogenous Cushing syndrome, either following surgery or not candidates for surgery
• Under consideration to receive osilodrostat as part of their clinical care
• Able to provide informed consent.

You may not qualify if:

• Treatment with other investigational drugs within 30 days or five half-lives (whichever is longer).
• A history of hypersensitivity to osilodrostat or therapies of a similar chemical class.

Sponsors & Collaborators

• University of Michigan: lead
• RECORDATI GROUP: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples for steroid measurements.

MeSH Terms

Conditions

Adrenal Insufficiency; Cushing Syndrome

Interventions

Osilodrostat

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases; Adrenocortical Hyperfunction

Study Officials

• Richard Auchus, MD, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Auchus

CONTACT

734-764-7764; rauchus@med.umich.edu

Thaira Blanco Varela

CONTACT

734-647-5661; tbv@med.umich.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Translational Medicine, Professor of Internal Medicine and Professor of Pharmacology

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: May 28, 2024
• Study Start: July 19, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)