Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06430528
Status:
RECRUITING
Last Update Posted:
2024-05-28
First Post:
2024-04-24
Brief Title:
A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement
Sponsor:
University of Michigan
Organization:
University of Michigan
Study Overview
Official Title:
A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 mgd 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 µgdL 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 µg24h Once the AM cortisol and UFC are at goals 5 µgdL and 10 µg24h 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
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 mgd 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 µgdL 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 µg24h Once the AM cortisol and UFC are at goals 5 µgdL and 10 µg24h 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None