Long Term Safety and Efficacy of Pasireotide s.c. in Patients With Cushing's Disease

Study Overview
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Brief Summary
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This is a non-interventional, multinational, multi-center post-marketing study, to further document the safety and efficacy of pasireotide s.c. administered in routine clinical practice in patients with Cushing's disease. Patients with Cushing's disease and treated with pasireotide s.c. alone and in combination with other therapies will be monitored. For this study, each enrolled patient will be followed up for 3 years after enrollment. Patients who permanently discontinue pasireotide s.c. prior to completing the 3-year observation period will be followed up for 3 months after the last dose of pasireotide s.c.

Official Title
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Non-interventional Study for the Generation of Long Term Safety and Efficacy Data of Pasireotide s.c. in Patients With Cushing's Disease (Post-Authorization Safety Study)

Conditions
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Cushings Disease

Intervention / Treatment
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* Drug: SOM230


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 18 years or older with a diagnosis of Cushing's disease for whom surgery has failed or for whom surgery is not an option Patients must be treated with pasireotide s.c. started either at the first visit for this study or prior to study entry Exclusion Criteria: Patients with ectopic ACTH-dependent Cushing's syndrome Patients with adrenal Cushing's syndrome Patients with Pseudo Cushing's syndrome

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pasireotide<br> | Drug: SOM230<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability profile of pasireotide s.c. | Number of pasireotide s.c related adverse events and serious adverse events, when administered as monotherapy or in combination with other therapies in patients with Cushing's disease | 3-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients that reach mean UFC ≤ ULN as short and long-term efficacy measure | The proportion of patients with a mean UFC ≤ ULN at 1, 3, 6, 12, 24 and 36 months after enrolling into the study | At 1, 3, 6, 12, 24 and 36 months after enrolling into the study | 
| Changes of mean UFC measures of disease activity | The absolute and percentage change from baseline of mean UFC measures of disease activity after enrolling into the study. | 3-year follow-up | 
| Proportion of patients achieving serum cortisol Normalization of disease activity | Proportion of patients achieving serum cortisol Normalization of disease activity where normalization refers to being within the upper and lower limit of normal ranges | 3-year follow-up | 
| The absolute and percentage change of blood pressure from baseline | The absolute and percentage change of blood pressure from baseline after enrolling into the study | 3-year follow-up | 
| The proportion of patients with favorable shift of blood pressure from baseline | The proportion of patients with favorable shift of blood pressure from baseline after enrolling into the study | 3-year follow-up | 
| Changes in safety and efficacy parameters over a period of 3 months | Safety parameters include: Adverse events , Serious Adverse Events, vital signs, blood pressure, heart rate, body temperature, blood glucose (fasting plasma glucose, HemoglobinA1c), hormones (IGF-1, GH, TSH/free T4), liver enzymes (AST, ALT, alkaline phosphatase, γGT, total bilirubin), hematology, electrolytes, immunological events (e.g., allergic reactions: rash, pruritus, injection site reactions), gallbladder ultrasound and ECGs. Efficacy parameters include: Urinary Free Cortisol, serum cortisol, serum cortisol after dexamethasone testing, salivary cortisol, plasma ACTH, fasting serum lipid profile, Blood pressure, body weight, body mass index, waist circumference, tumor size and quality of life. | 3 months after patient's discontinuation | 
| The absolute and percentage change in tumor size | The absolute and percentage change in tumor size after enrolling into the study | 3-year follow-up | 
| The absolute and percentage change from baseline in patient-reported outcome questionnaires | The absolute and percentage change from baseline in patient -reported outcome questionnaires (Cushing QoL and EURO QoL) after enrolling into the study | 3-year follow-up | 
| Change of serum cortisol measures of disease activity | The absolute and percentage change from baseline of serum cortisol measures of disease activity after enrolling into the study | 3-year follow-up | 
| Change of serum cortisol after dexamathasone testing measures of disease activity | The absolute and percentage change from baseline of serum cortisol after dexamathasone testing measures of disease activity after enrolling into the study | 3-year followup | 
| Changes of salivary cortisol measures of disease activity | The absolute and percentage change from baseline of salivary cortisol measures of disease activity after enrolling into the study | 3-year follow-up | 
| Changes of ACTH measures of disease activtity | The absolute and percentage change from baseline of ACTH measures of disease activity after enrolling into the study | 3-year follow-up | 
| Proportion of patients achieving serum cortisol after dexamethasone testing Normalization of disease activity | Proportion of patients achieving serum cortisol after dexamethasone testing Normalization of disease activity where normalization refers to being within the upper and lower limit of normal ranges | 3-year follow-up | 
| Proportion of patients achieving salivary cortisol Normalization of disease activity | Proportion of patients achieving salivary cortisol of disease activity where normalization refers to being within the upper and lower limit of normal ranges | 3-year follow-up | 
| Proportion of patients achieving ACTH Normalization of disease activity | Proportion of patients achieving ACTH of disease activity where normalization refers to being within the upper and lower limit of normal ranges | 3-year follow-up | 
| Changes of fasting serum lipid profile measures of disease activtity | The absolute and percentage change from baseline of fasting serum lipid profile measures of disease activity after enrolling into the study | 3-year follow-up | 
| The absolute and percentage change of body weight from baseline | The absolute and percentage change of body weight from baseline after enrolling into the study | 3-year follow-up | 
| The absolute and percentage change of body mass index from baseline | The absolute and percentage change of body mass index from baseline after enrolling into the study | 3-year follow-up | 
| The absolute and percentage change of waist circumference from baseline | The absolute and percentage change of waist circumference from baseline after enrolling into the study | 3-year follow-up | 
| The proportion of patients with favorable shift of body weight from baseline | The proportion of patients with favorable shift of body weight from baseline after enrolling into the study | 3-year follow-up | 
| The proportion of patients with favorable shift of body mass index from baseline | The proportion of patients with favorable shift of body mass index from baseline after enrolling into the study | 3-year follow-up | 
| The proportion of patients with favorable shift of waist circumference from baseline | The proportion of patients with favorable shift of waist circumference from baseline after enrolling into the study | 3-year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cushing's disease,, pasireotide s.c., Signifor