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

Study Overview
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Brief Summary
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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.

Official Title
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A Retrospective Observational Study to Evaluate the Safety and Effectiveness of Osilodrostat for the Treatment of Non-Cushing's Disease Cushing's Syndrome (LINC7)

Conditions
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Cushing's Syndrome

Intervention / Treatment
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* Drug: Osilodrostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Patients treated with osilodrostat between April 2019 and study start date as part of ATU programme or commercialisation. Exclusion Criteria: Patients who participated in a clinical trial anytime during the study period. Patients with Pseudo-Cushing's syndrome, cyclic CS, or iatrogenic CS.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Osilodrostat|oral administration|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Urinary Free Cortisol (mUFC) | Number and proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Urinary Free Cortisol (mUFC) | Proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN) | 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. | 
| Morning serum cortisol | Change from baseline | 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. | 
| Mean Urinary Free Cortisol (mUFC) | Change from baseline | 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. | 
| Body Mass Index (BMI) | Actual and percentage change from Baseline | 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. | 
| Electrocardiogram (ECG) | Actual and percentage change from Baseline | 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. | 
| Co-morbidities | Actual and percentage change from Baseline | 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. | 
| Blood Pressure | Actual and percentage change from Baseline | 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. | 
| Sodium | Actual and percentage change from Baseline | 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. | 
| Potassium | Actual and percentage change from Baseline | 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. | 
| Calcium | Actual and percentage change from Baseline | 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. | 
| CO2 | Actual and percentage change from Baseline | 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. | 
| Glucose Levels | Actual and percentage change from Baseline | 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. | 
| Glycated haemoglobin (HBA1c) | Actual and percentage change from Baseline | 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. | 
| Plasma Adrenocorticotropic hormone (ACTH) | Actual and percentage change from Baseline | 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. | 
| Serum 11-Deoxycortisol | Actual and percentage change from Baseline | 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. | 
| Plasma 11-Deoxycorticosterone | Actual and percentage change from Baseline | 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. | 
| Plasma Aldosterone | Actual and percentage change from Baseline | 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. | 
| Plasma Renin | Actual and percentage change from Baseline | 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. | 
| Total Serum Testosterone or oestradiol (per patient sex) | Actual and percentage change from Baseline | 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. | 
| Serum LH | Actual and percentage change from Baseline | 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. | 
| Serum FSH | Actual and percentage change from Baseline | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endogenous Cushing's Syndrome, Cushing's Syndrome, Osilodrostat