Osilodrostat for the Treatment of Non-Cushing's Disease Cushing's Syndrome (LINC7)

• ClinicalTrials.gov Identifier: NCT05633953
• Recruitment Status: Completed
• First Posted: December 1, 2022
• Last Update Posted: April 26, 2024
• Sponsor: RECORDATI GROUP
• Information provided by (Responsible Party): RECORDATI GROUP

Study Description

Brief Summary:

This is a multi-centre, observational, non-comparative, retrospective cohort study designed to evaluate the long-term safety and effectiveness of osilodrostat in non-CD CS patients. Patients treated with oral osilodrostat regardless of the duration of their treatment will be followed retrospectively for up to 36 months after initiating osilodrostat.

Condition or disease	Intervention/treatment
Cushing's Syndrome	Drug: Osilodrostat

Study Design

• Study Type: Observational
• Actual Enrollment: 104 participants
• Observational Model: Other
• Time Perspective: Retrospective
• Official Title: A Retrospective Observational Study to Evaluate the Safety and Effectiveness of Osilodrostat for the Treatment of Non-Cushing's Disease Cushing's Syndrome (LINC7)
• Actual Study Start Date: January 16, 2023
• Actual Primary Completion Date: September 30, 2023
• Actual Study Completion Date: October 30, 2023

Groups and Cohorts

Intervention Details:

• Drug: Osilodrostat
  oral administration

Outcome Measures

Primary Outcome Measures :

1. Mean Urinary Free Cortisol (mUFC) [ Time Frame: 12 weeks ]
   Number and proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN)

Secondary Outcome Measures :

1. Mean Urinary Free Cortisol (mUFC) [ Time Frame: At Weeks 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN)
2. Morning serum cortisol [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Change from baseline
3. Mean Urinary Free Cortisol (mUFC) [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Change from baseline
4. Body Mass Index (BMI) [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Actual and percentage change from Baseline
5. Electrocardiogram (ECG) [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Actual and percentage change from Baseline
6. Co-morbidities [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Actual and percentage change from Baseline
7. Blood Pressure [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Actual and percentage change from Baseline
8. Sodium [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Actual and percentage change from Baseline
9. Potassium [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
   Actual and percentage change from Baseline
10. Calcium [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
11. CO2 [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
12. Glucose Levels [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
13. Glycated haemoglobin (HBA1c) [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
14. Plasma Adrenocorticotropic hormone (ACTH) [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
15. Serum 11-Deoxycortisol [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
16. Plasma 11-Deoxycorticosterone [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
17. Plasma Aldosterone [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
18. Plasma Renin [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
19. Total Serum Testosterone or oestradiol (per patient sex) [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
20. Serum LH [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline
21. Serum FSH [ Time Frame: At Weeks 4, 8, 12, 18, 24, 36 of treatment and every additional 12 weeks of treatment until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. ]
    Actual and percentage change from Baseline

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of patients with non-CD CS. Patients meeting eligibility criteria will be retrospectively identified and included in the study by site investigators based on a review of medical records at site. Site policies and local regulations regarding patient consent (NOL) will be followed. All eligible patients identified at a site between April 2019 and study start date and consenting to be part of the study will be included.

Criteria

Inclusion Criteria:

1. Male and female patients ≥18 years old with diagnosis of CS, except for CD (i.e., an aetiology of adrenal adenoma, adrenocortical carcinoma, adrenal hyperplasia, or ectopic adrenocorticotropic hormone secretion). Patients should have a contemporaneously documented diagnosis of CS as per effective guidelines.
2. Patients treated with osilodrostat between April 2019 and study start date as part of ATU programme or commercialisation.

Exclusion Criteria:

1. Patients who participated in a clinical trial anytime during the study period.
2. Patients with Pseudo-Cushing's syndrome, cyclic CS, or iatrogenic CS.

Contacts and Locations

Locations

France

Hôpital Haut-Lévèque

Pessac, France, 33604

Sponsors and Collaborators

RECORDATI GROUP

Investigators

• Study Director: Mario M MALDONADO, MD; RECORDATI GROUP

More Information

• Responsible Party: RECORDATI GROUP
• ClinicalTrials.gov Identifier: NCT05633953
• Other Study ID Numbers: LCI699-RECAG-NI-0596
• First Posted: December 1, 2022
• Last Update Posted: April 26, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by RECORDATI GROUP:

Endogenous Cushing's Syndrome; Cushing's Syndrome; Osilodrostat

Additional relevant MeSH terms:

Cushing Syndrome; Syndrome; Disease; Pathologic Processes; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases