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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: 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)

Brief Summary: 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.

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Number of Participants with Adverse Events as a Measure of Safety and Tolerability profile of pasireotide s.c. [ Time Frame: 3-year follow-up ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• The proportion of patients that reach mean UFC ≤ ULN as short and long-term efficacy measure [ Time Frame: At 1, 3, 6, 12, 24 and 36 months after enrolling into the study ]
  The proportion of patients with a mean UFC ≤ ULN at 1, 3, 6, 12, 24 and 36 months after enrolling into the study
• Changes of mean UFC measures of disease activity [ Time Frame: 3-year follow-up ]
  The absolute and percentage change from baseline of mean UFC measures of disease activity after enrolling into the study.
• Proportion of patients achieving serum cortisol Normalization of disease activity [ Time Frame: 3-year follow-up ]
  Proportion of patients achieving serum cortisol Normalization of disease activity where normalization refers to being within the upper and lower limit of normal ranges
• The absolute and percentage change of blood pressure from baseline [ Time Frame: 3-year follow-up ]
  The absolute and percentage change of blood pressure from baseline after enrolling into the study
• The proportion of patients with favorable shift of blood pressure from baseline [ Time Frame: 3-year follow-up ]
  The proportion of patients with favorable shift of blood pressure from baseline after enrolling into the study
• Changes in safety and efficacy parameters over a period of 3 months [ Time Frame: 3 months after patient's discontinuation ]
  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.
• The absolute and percentage change in tumor size [ Time Frame: 3-year follow-up ]
  The absolute and percentage change in tumor size after enrolling into the study
• The absolute and percentage change from baseline in patient-reported outcome questionnaires [ Time Frame: 3-year follow-up ]
  The absolute and percentage change from baseline in patient -reported outcome questionnaires (Cushing QoL and EURO QoL) after enrolling into the study
• Change of serum cortisol measures of disease activity [ Time Frame: 3-year follow-up ]
  The absolute and percentage change from baseline of serum cortisol measures of disease activity after enrolling into the study
• Change of serum cortisol after dexamathasone testing measures of disease activity [ Time Frame: 3-year followup ]
  The absolute and percentage change from baseline of serum cortisol after dexamathasone testing measures of disease activity after enrolling into the study
• Changes of salivary cortisol measures of disease activity [ Time Frame: 3-year follow-up ]
  The absolute and percentage change from baseline of salivary cortisol measures of disease activity after enrolling into the study
• Changes of ACTH measures of disease activtity [ Time Frame: 3-year follow-up ]
  The absolute and percentage change from baseline of ACTH measures of disease activity after enrolling into the study
• Proportion of patients achieving serum cortisol after dexamethasone testing Normalization of disease activity [ Time Frame: 3-year follow-up ]
  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
• Proportion of patients achieving salivary cortisol Normalization of disease activity [ Time Frame: 3-year follow-up ]
  Proportion of patients achieving salivary cortisol of disease activity where normalization refers to being within the upper and lower limit of normal ranges
• Proportion of patients achieving ACTH Normalization of disease activity [ Time Frame: 3-year follow-up ]
  Proportion of patients achieving ACTH of disease activity where normalization refers to being within the upper and lower limit of normal ranges
• Changes of fasting serum lipid profile measures of disease activtity [ Time Frame: 3-year follow-up
  
  

  Original Secondary Outcome:

  • The proportion of patients that reach mean UFC ≤ ULN as short and long-term efficacy measure [ Time Frame: At 1, 3, 6, 12, 24 and 36 months after enrolling into the study ]
    The proportion of patients with a mean UFC ≤ ULN at 1, 3, 6, 12, 24 and 36 months after enrolling into the study
  • Changes of mean UFC measures of disease activity [ Time Frame: 3-year follow-up ]
    The absolute and percentage change from baseline of mean UFC measures of disease activity after enrolling into the study.
  • Proportion of patients achieving serum cortisol Normalization of disease activity [ Time Frame: 3-year follow-up ]
    Proportion of patients achieving serum cortisol Normalization of disease activity where normalization refers to being within the upper and lower limit of normal ranges
  • The absolute and percentage change of blood pressure from baseline [ Time Frame: 3-year follow-up ]
    The absolute and percentage change of blood pressure from baseline after enrolling into the study
  • The proportion of patients with favorable shift of blood pressure from baseline [ Time Frame: 3-year follow-up ]
    The proportion of patients with favorable shift of blood pressure from baseline after enrolling into the study
  • Changes in safety and efficacy parameters over a period of 3 months including: adverse events, immunological events, cortisol, tumor size, etc. [ Time Frame: 3 months after patient's discontinuation ]
    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.
  • The absolute and percentage change in tumor size [ Time Frame: 3-year follow-up ]
    The absolute and percentage change in tumor size after enrolling into the study
  • The absolute and percentage change from baseline in patient-reported outcome questionnaires [ Time Frame: 3-year follow-up ]
    The absolute and percentage change from baseline in patient -reported outcome questionnaires (Cushing QoL and EURO QoL) after enrolling into the study
  • Change of serum cortisol measures of disease activity [ Time Frame: 3-year follow-up ]
    The absolute and percentage change from baseline of serum cortisol measures of disease activity after enrolling into the study
  • Change of serum cortisol after dexamathasone testing measures of disease activity [ Time Frame: 3-year followup ]
    The absolute and percentage change from baseline of serum cortisol after dexamathasone testing measures of disease activity after enrolling into the study
  • Changes of salivary cortisol measures of disease activity [ Time Frame: 3-year follow-up ]
    The absolute and percentage change from baseline of salivary cortisol measures of disease activity after enrolling into the study
  • Changes of ACTH measures of disease activtity [ Time Frame: 3-year follow-up ]
    The absolute and percentage change from baseline of ACTH measures of disease activity after enrolling into the study
  • Proportion of patients achieving serum cortisol after dexamethasone testing Normalization of disease activity [ Time Frame: 3-year follow-up ]
    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
  • Proportion of patients achieving salivary cortisol Normalization of disease activity [ Time Frame: 3-year follow-up ]
    Proportion of patients achieving salivary cortisol of disease activity where normalization refers to being within the upper and lower limit of normal ranges
  • Proportion of patients achieving ACTH Normalization of disease activity [ Time Frame: 3-year follow-up ]
    Proportion of patients achieving ACTH of disease activity where normalization refers to being within the upper and lower limit of normal ranges
  • Changes of fasting serum lipid profile
    
    Information By: Novartis
    

    Dates:
    Date Received: September 26, 2014
    Date Started: March 2013
    Date Completion: April 2024
    Last Updated: January 27, 2017
    Last Verified: January 2017