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

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)

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.

Study Overview

• Status: Completed
• Conditions: Cushings Disease
• Intervention / Treatment: Drug: Pasireotide

• Study Type: Observational
• Enrollment (Actual): 152

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G2
    • CHUL Centre de recherche du CHU
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre de recherche du CHUM CRCHUM
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CHUS - Hopital Fleurimont
• Colombia
  • Cali, Colombia
    • Centro Medico Imbanaco de Cali
• France
  • Amiens Cedex 1, France, 80054
    • CHU Amiens Picardie site Nord
  • Bron Cedex, France, 69677
    • HCL-Groupe Hospitalier Est
  • Lille Cedex, France, 59037
    • Recordati Investigative Site
  • Marseille, France, 13385
    • AP-HM - Hopital de La Conception
  • Montpellier Cedex 5, France, 34295
    • Hopital Lapeyronie
  • Paris, France, 75014
    • Hôpital Cochin
  • Reims, France, 51092
    • Hopital Robert Debre
  • Saint Mande, France, 94160
    • HIA Begin
  • St Priest en Jarez Cedex, France, 42277
    • Chu de Saint Etienne
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum Aachen
  • Berlin, Germany, 13353
    • Universitaetsmedizin Charite
  • Duesseldorf, Germany, 40225
    • Univ.-Klinikum Düsseldorf
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen Nuernberg
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Halle, Germany, 06108
    • Praxis Dr.med.Frank Ackermann
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg Eppendorf
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig AöR
  • Magdeburg, Germany, 39120
    • Universitaetsklinikum Magdeburg AöR
  • Muenchen, Germany, 81377
    • Universitaetsklinikum Muenchen LMU
  • Muenchen, Germany, 81667
    • Medicover Muenchen Ost MVZ
  • Oldenburg, Germany, 26122
    • Praxis Michael Droste
  • Wuerzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
• Israel
  • Petach Tikva, Israel, 49100
    • Rabin Medical Centre Belinson
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Centre Ichilov
• Italy
  • Napoli, Italy, 80131
    • O Universitaria Policlinico Federico II Univ Studi Fed II
  • AN
    • Ancona, AN, Italy, 60126
      • AOU Osp Riuniti Umberto I GM Lancisi G Salesi Univ Studi
  • ME
    • Messina, ME, Italy, 98125
      • Az.Ospe.Universitaria Policlinico G. Martino Univ.di Messina
  • MI
    • Milano, MI, Italy, 20122
      • Fond IRCCS Ca Granda Ospedale Maggiore Policlinico
    • Milano, MI, Italy, 20149
      • Stab.Osp.S.Luca P.O. S.Luca-S.Michele-Ist.Auxol. Italiano
  • PA
    • Palermo, PA, Italy, 90127
      • Az Osp Univ Policlinico P Giaccone Universita Studi Palermo
  • PD
    • Padova, PD, Italy, 35128
      • Azienda Ospedaliera di Padova Università degli Studi
  • PI
    • Pisa, PI, Italy, 56124
      • Az Ospedaliero Universitaria Pisana Pres Osped di Cisanello
  • TO
    • Torino, TO, Italy, 10126
      • P O Molinette AO Citta della Salute e della Scienza Torino
• Lebanon
  • El Achrafiyé, Lebanon, 166830
    • Hotel Dieu de France Hospital
• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • Radboudumc
  • AZ
    • Maastricht, AZ, Netherlands, 5800
      • Maastricht Universitair Medisch Centrum
• Romania
  • Brasov, Romania, 500365
    • Spitalul Clinic Judetean de Urgenta Brasov
  • Bucuresti, Romania, 011863
    • Institutul de Endocrinologie "I. C. Parhon", Bucuresti
  • Cluj, Romania, 400006
    • Spitalul Clinic Jude Emergency Clinical County Hospital Cluj
  • Târgu-Mureş, Romania, 540061
    • County Hospital Tg. Mures
• United Kingdom
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St Josephs Hospital and Medical Center
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California CSOM230B2410 - SC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital SC - SOM230B2410
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University SC - SOM230B2410
  • Oregon
    • Bend, Oregon, United States, 97702
      • Endocrinology Services
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Endocrinology Associates
  • Washington
    • Seattle, Washington, United States, 98122-4379
      • Swedish Medical Center Dept.ofSeattle Neuroscience(2)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The patient population will consist of male and 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 and who are treated with pasireotide s.c.

Description

Inclusion Criteria:

• Written informed consent or equivalent document (e.g., written information) as per country regulation prior to registration of any patient data
• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1/new use cohort; Subjects who initiated pasireotide s.c. at time of study entry (on or after the signing of the informed consent or acknowledging an equivalent document -for example, written information- as per country regulation).	Drug: Pasireotide; Other Names: Signifor
Cohort 2/prior use cohort; Subjects who initiated pasireotide s.c. prior to study entry.	Drug: Pasireotide; Other Names: Signifor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: RECORDATI GROUP
• Investigators: Study Director: Mario MALDONADO, MD, Recordati AG

Publications and helpful links

General Publications

• Manetti L, Deutschbein T, Schopohl J, Yuen KCJ, Roughton M, Kriemler-Krahn U, Tauchmanova L, Maamari R, Giordano C. Long-term safety and efficacy of subcutaneous pasireotide in patients with Cushing's disease: interim results from a long-term real-world evidence study. Pituitary. 2019 Oct;22(5):542-551. doi: 10.1007/s11102-019-00984-6.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2013
• Primary Completion (Actual): July 10, 2023
• Study Completion (Actual): July 10, 2023

Study Registration Dates

• First Submitted: September 26, 2014
• First Submitted That Met QC Criteria: December 5, 2014
• First Posted (Estimated): December 8, 2014

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: July 19, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Cushing's disease,; pasireotide s.c.; Signifor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Adenoma; Pituitary Neoplasms; ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: CSOM230B2410