Non-interventional Study on Osilodrostat in Patients With Endogenous Cushing's Syndrome

Study Overview
=================
Brief Summary
-----------------
This is a non-interventional, multinational, multi-centre study with primary data collection, to further document the safety and efficacy of osilodrostat administered in routine clinical practice in patients treated with osilodrostat for endogenous Cushing's Syndrome

Detailed Description
-----------------
This is a non-interventional, multinational, multi-centre study with primary data collection, to further document the safety and efficacy of osilodrostat administered in routine clinical practice in patients treated with osilodrostat for endogenous Cushing's Syndrome. This study is observational in nature and does not impose a therapy protocol, diagnostic/therapeutic interventions or a visit schedule. Patients with endogenous Cushing's Syndrome who are treated with osilodrostat alone or in combination with other therapies will be considered eligible for study enrolment. Each patient enrolled in the study will be followed up for 3 years from study entry. Patients who discontinue prior to the end of the 3-year period will be followed-up for 3 months after discontinuation of osilodrostat and will be included in the analysis. The total number of patients enrolled in this study will be at least 100. Assuming a recruitment period of 3 years, the total study duration from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) will be 6 years. The maximum duration for the individual patient is 3 years.

Official Title
-----------------
A Non-interventional Study to Assess the Long-term Safety and Efficacy of Osilodrostat in Patients With Endogenous Cushing's Syndrome

Conditions
-----------------
Endogenous Cushing's Syndrome

Intervention / Treatment
-----------------
* Drug: Osilodrostat


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent obtained prior to registration of any patient data Male or female patients aged 18 years or older with endogenous CS treated with osilodrostat. Treatment with osilodrostat can either be initiated at the first visit of the study or can have been initiated before screening. Exclusion Criteria: Patients with exogenous CS Patients with Pseudo CS Patients participating in an interventional clinical trial with an investigational drug.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Osilodrostat<br>Osilodrostat - tablets of 1mg, 5mg, 10mg - based on patients needs - up to 3 years | Drug: Osilodrostat<br>* oral administration of Osilodrostat tablets at different doses according to patient's need<br>* Other names: Isturisa;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of osilodrostat-related adverse events and serious adverse events | Number of participants with Adverse Events and Serious Adverse Events | 3 years of treatment with osilodrostat | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short and long-term efficacy of osilodrostat | Complete response rate: proportion of enrolled patients with mean Urinary Free Cortisol (mUFC) ≤ ULN | at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years | 
| Short and long-term efficacy of osilodrostat | Partial response rate: proportion of enrolled patients with ≥ 50% reduction from baseline in mean urinary free cortisol (mUFC), (but mUFC > ULN) | at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years | 
| Short and long-term efficacy of osilodrostat | Overall response rate: proportion of enrolled patients with mean urinary free cortisol (mUFC) ≤ ULN or at least 50% reduction from baseline | at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years | 
| Changes in pituitary tumour size | Actual and percentage change from baseline in pituitary tumour size | at baseline before treatment start, after 6 months of treatment, then every 12 months through study completion up to three years | 
| Incidence of Adverse Events (Safety and Tolerability) | Incidence of adverse events and laboratory abnormalities using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale (version 5.0). | 3 years of treatment with osilodrostat | 
| Change of mean urinary free cortisol (mUFC) | Actual and percentage change from baseline in mean urinary free cortisol (mUFC) | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Change of Serum Cortisol | Actual and percentage change from baseline in Serum Cortisol | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Change of Late Salivary Cortisol | Actual and percentage change from baseline in Late Salivary Cortisol | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Change of adrenocorticotropic hormone (ACTH) | Actual and percentage change from baseline in adrenocorticotropic hormone (ACTH) | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Normalization of Serum Cortisol | Proportion of patients achieving normalisation of Serum Cortisol | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Normalization of Late Salivary Cortisol | Proportion of patients achieving normalisation of Late Salivary Cortisol | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Normalization of adrenocorticotropic hormone (ACTH) | Proportion of patients achieving normalisation of adrenocorticotropic hormone (ACTH) | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Change in Fasting Glucose | Actual and percentage change from baseline in fasting glucose | at baseline before treatment start, then every 3 months through study completion up to three years | 
| Change in HbA1c | Actual and percentage change from baseline in HbA1c | at baseline before treatment start, then every 3 months through study completion up to three years | 
| Change in Fasting Lipid Profile | Actual and percentage change from baseline in Fasting Lipid Profile | at baseline before treatment start, then every 3 months through study completion up to three years | 
| Change in Serum Insulin | Actual and percentage change from baseline in Serum Insulin | at baseline before treatment start, then every 3 months through study completion up to three years | 
| Change in Blood Pressure | Actual and percentage change from baseline in Blood Pressure | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Change in Body Weight | Actual and percentage change from baseline in Body Weight | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Change in Body Mass Index (BMI) | Actual and percentage change from baseline in Body Mass Index (BMI) | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Change in Waist Circumference | Actual and percentage change from baseline in Waist Circumference | at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years | 
| Change in Facial Rubor | Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Facial Rubor | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Change in Hirsutism | Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Hirsutism | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Change in Striae | Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Striae | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Change in Supraclavicular fat pad | Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Supraclavicular fat pad | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Change in Dorsal fat pad | Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Dorsal fat pad | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Change in Proximal muscle wasting (atrophy) | Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Proximal muscle wasting (atrophy) | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Change in Central (abdominal) obesity | Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Central (abdominal) obesity | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Change in Ecchymoses (bruises) | Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Ecchymoses (bruises) | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Changes in Patient-Reported Outcome (PRO) questionnaire Cushing Quality of Life (QoL) | Actual and percentage change from baseline in score of PRO questionnaire CushingQoL. The minimum and maximum values are 12 and 60 respectively, where higher score means a better outcome | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Changes in Patient-Reported Outcome (PRO) questionnaire Euro Quality of Life (EQ) - 5 Dimensions (5D) - 5 Levels (5L) | Actual and percentage change from baseline in score of PRO questionnaire EQ-5D-5L. The minimum and maximum values for the questions are 11111 and 55555 respectively, where higher score is a worst outcome. For the visual analogue scale minimum and maximum values are 0 and 100 respectively, where higher score means a better outcome | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Changes in Patient-Reported Outcome (PRO) questionnaire Beck Depression Inventory II (BDI-II) | Actual and percentage change from baseline in score of PRO questionnaire BDI-II. The minimum and maximum values are 1 and 63 respectively, where higher score means a worse outcome | at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 
| Changes in Patient-Reported Outcome (PRO) questionnaire Patient Global Impression of Change (PGIC) | Actual and percentage change in score of PRO questionnaire PGIC. The minimum and maximum values of the question are 1 and 7 respectively, where higher score means a better outcome. For the visual analogue scale minimum and maximum values are 0 and 10 respectively, where higher score means a worse outcome | after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cushing's syndrome, Osilodrostat