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

NCT ID: NCT06430528

Last Updated: 2025-08-20

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 12 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-07-19
• Study Completion Date: 2027-08-31

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.

Detailed Description

Phase 1 (Titration):

Participants will provide written informed consent and receive the first dose of osilodrostat (1-2 mg) in the evening. The following morning, participants will add treatment with at least a physiologic replacement dose of methylprednisolone (4-6 mg/d based on body size in not more than 2 divided doses) and concurrently continue 1-2 mg BID of osilodrostat. Frequent communication is maintained with each participant, at least twice weekly for the first 3 months and weekly thereafter until target osilodrostat dose is reached. Study personnel will ask targeted questions related to the primary endpoint with parameters to notify the study physicians for early signs of adrenal insufficiency. Participants are instructed to double their methylprednisolone dose for intercurrent illness and for symptoms of cortisol deficiency or withdrawal that do not resolve with pausing osilodrostat dosing. Every 4-12 weeks, an AM cortisol, as well as a research sample for steroid profiling (including 11OHA4), is obtained prior to the first doses of methylprednisolone and osilodrostat. The osilodrostat dose is up-titrated as necessary to achieve an AM cortisol goal of <5 µg/dL. Once the AM cortisol is at goal, a late-night saliva cortisol (LNSC) and 24 h urine free cortisol (UFC) is obtained per standard of care. Osilodrostat titration is continued if necessary until the UFC is also at goal of <10 µg/24h. Once the AM cortisol and UFC are at goals (<5 µg/dL and <10 µg/24h, respectively), the primary endpoint measures are completed, and the participant enters Phase 2.

Phase 2 (Maintenance):

Once the participant reaches what the investigator considers the maintenance doses of osilodrostat and methylprednisolone, participants are followed for a total of 48 weeks from the first osilodrostat dose before being considered at the end of study. The AM serum cortisol, UFC, and LNSC are repeated at the end of the 48-week period and as clinically indicated throughout Phase 2, generally every 3-6 months.

Conditions

Endogenous Cushing Syndrome; Adrenal Insufficiency; Hypercortisolism

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Observational cohort

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

Osilodrostat

Intervention Type: DRUG

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

Interventions

Osilodrostat

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

Intervention Type: DRUG

Other Intervention Names

Isturisa

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Recordati Rare Diseases

INDUSTRY

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Richard J. Auchus, MD PhD

Professor of Translational Medicine, Professor of Internal Medicine and Professor of Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard Auchus, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Richard Auchus

Role: CONTACT

rauchus@med.umich.edu

734-764-7764

Thaira Blanco Varela

Role: CONTACT

tbv@med.umich.edu

734-647-5661

Facility Contacts

Eyad Alsafadi

Role: primary

alsafade@med.umich.edu

734-647-5661

Thaira Blanco Varela

Role: backup

tbv@med.umich.edu

734-647-5661

Other Identifiers

HUM00246263

Identifier Type: -

Identifier Source: org_study_id