Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00434148
First received: February 9, 2007
Last updated: August 6, 2015
Last verified: August 2015
  Purpose

This study will evaluate the safety and efficacy of two different doses of Pasireotide in patients with de novo or recurrent/persistent Cushing's Disease.


Condition Intervention Phase
Cushing's Disease
Drug: Pasireotide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Study to Assess the Safety and Efficacy of Different Dose Levels of Pasireotide (SOM230) Subcutaneous (sc) Over a 6 Month Treatment Period in Patients With de Novo, Persistent or Recurrent Cushing's Disease

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    A responder in the primary efficacy analysis was a patient with a mUFC≤ULN at Month 6 and whose dose was not increased prior to Month 6.


Secondary Outcome Measures:
  • Change From Baseline in mUFC [ Time Frame: baseline, 3 months, 12 months ] [ Designated as safety issue: No ]
    Twenty four hour urine samples were collected to obtain mUFC measurements. A negative change from baseline indicates improvement.

  • Time to First UFC Response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Time to first UFC response is defined as the number of months from baseline to first attainment of UFC response.

  • Percent Change From Baseline in Serum Cortisol [ Time Frame: baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months ] [ Designated as safety issue: No ]
    Blood samlpes were drawn to obtain serum cortisol levels. A negative change from baseline indicates improvement.

  • Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) [ Time Frame: baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months ] [ Designated as safety issue: No ]
    Blood samples were drawn to obtain ACTH levels. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ] [ Designated as safety issue: No ]
    Sitting blood pressure assessments were performed at every study visit. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60 ] [ Designated as safety issue: No ]
    BMI was determined by using height and weight measurements. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ] [ Designated as safety issue: No ]
    Waist circumference was measured with a measuring tape correctly positioned. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ] [ Designated as safety issue: No ]
    Blood samples were drawn to obtain total cholesterol and triglycerides' levels. A negative change from baseline indicates improvement.

  • Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score [ Time Frame: baseline, month 3, month 6, month 12, month 18, month 24 ] [ Designated as safety issue: No ]

    The BDI-II is a 21 item self-report rating inventory measuring characteristic attitudes and symptoms of depression. The BDI-II contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The scores range as follows:

    0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; and 29-63: severe depression. A negative change from baseline indicates imrpovement.


  • Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ] [ Designated as safety issue: No ]
    The Ferriman Gallwey scoring system is used to score the degree of excess male pattern body hair. The scorecard of every body location under survey begins from 0 (no excessive terminal hair growth) to 4 (extensive terminal hair growth) and the numbers are added up to a maximum count of 36. A score >= 6 indicates the hirsutism. A negative change from baseline indicates imrpovement.

  • Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ] [ Designated as safety issue: No ]
    BMD was measured using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done in the lumbar vertebrae (L1-L4), proximal femur (total hip) and proximal femur (femur neck). A negative change from baseline indicates imrpovement.

  • Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition [ Time Frame: baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 ] [ Designated as safety issue: No ]
    Body composition as in percentage of body fat by region was assessed by total body scan. A negative change from baseline indicates improvement.

  • Change From Baseline in Tumor Volume [ Time Frame: baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 months ] [ Designated as safety issue: No ]
    Pituitary magnetic resonance imaging (MRI) was performed to determine tumor volume. A negative change from baseline indicates imrpovement.

  • Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score [ Time Frame: baseline, 3 months, 6 months, 12 months ] [ Designated as safety issue: No ]
    A Cushing's syndrome health related quality of life (HRQL) questionnaire was completed. The Cushing's Syndrome HRQL questionnaire contains 12 sentences with 5 possible answers each. The answers are based on Likert scales, with 5 response categories: Always, Often, Sometimes, Rarely and Never; or Very much, Quite a bit, Somewhat, Very little, and Not at all. The answers to each of the items are rated on a scale of 1 to 5. "1" corresponds to the response category "Always" or "Very much" and "5" corresponds to the category "Never" or "Not at all". The score is the sum of all item responses and can range from 12 to 60 points. The lower the score, the greater the Cushing's Syndrome impacts on HRQoL. A positive change from baseline indicates improvement.


Enrollment: 162
Study Start Date: December 2006
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pasireotide 600 ug
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
Drug: Pasireotide
Experimental: Pasireotide 900 ug
At randomization, participants received 900 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
Drug: Pasireotide

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • 18 years or greater
  • Confirmed diagnosis of ACTH-dependent Cushing's disease
  • Not considered candidate for pituitary surgery

Exclusion criteria

  • History of pituitary irradiation in the last 10 years
  • Cushing's syndrome not caused by pituitary tumor
  • Patients with active malignant disease (cancer) in the last 5 years
  • Women who are pregnant or lactating

Other protocol-defined inclusion/exclusion criteria apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00434148

  Hide Study Locations
Locations
United States, California
Stanford University Medical Center Stanford Cancer Center (3)
Stanford, California, United States, 94304
United States, Illinois
University Chicago Hospital Dept. of Univ of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Dana Farber Cancer Institute The Melanoma Program
Boston, Massachusetts, United States, 02115
United States, New York
Columbia University Medical Center- New York Presbyterian Columbia University DeptofMed
New York, New York, United States, 10032
United States, Ohio
Cleveland Clinic Foundation Dept. of Cleveland Clinic (6)
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health & Sciences University Dept.ofOregonHealth&SciencesU.
Portland, Oregon, United States, 97239
United States, Texas
University of Texas Southwestern Medical Center Clinical-TranslationalRes.Ctr.
Dallas, Texas, United States, 75390-8527
University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(8)
Houston, Texas, United States, 77030-4009
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Swedish Medical Center Dept.ofSeattle Neuroscience(2)
Seattle, Washington, United States
Argentina
Novartis Investigative Site
Capital Federal, Buenos Aires, Argentina, 1425EKP
Novartis Investigative Site
Buenos Aires, Argentina, C1405BCH
Novartis Investigative Site
Buenos Aires, Argentina, C1232AAC
Belgium
Novartis Investigative Site
Edegem, Belgium, 2650
Novartis Investigative Site
Gent, Belgium, 9000
Brazil
Novartis Investigative Site
Curitiba, PR, Brazil, 80060-900
Novartis Investigative Site
Rio de Janeiro, RJ, Brazil, 21941-913
Novartis Investigative Site
Porto Alegre, RS, Brazil, 90035-903
Novartis Investigative Site
Ribeirao Preto, SP, Brazil, 14048-900
Novartis Investigative Site
Sao Paulo, SP, Brazil, 05403-000
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São Paulo, SP, Brazil, 01401-901
Canada, Alberta
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Edmonton, Alberta, Canada, T6G 2S2
Canada, Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H2W 1T8
China, Beijing
Novartis Investigative Site
Beijing, Beijing, China, 100730
China
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Beijing, China, 100028
Novartis Investigative Site
Shanghai, China, 200025
Denmark
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Arhus, Denmark, 8000
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Copenhagen, Denmark, DK-2100
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Herlev, Denmark, DK-2730
Finland
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Helsinki, Finland, FIN-00290
France
Novartis Investigative Site
Angers, France, 49033
Novartis Investigative Site
Grenoble Cédex 9, France, 38043
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LILLE Cedex, France, 59037
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Limoges cedex, France, 87042
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Marseille cedex 05, France, 13385
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Paris, France, 75014
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Pessac Cedex, France, 33604
Novartis Investigative Site
St Priest en Jarez Cedex, France, 42277
Novartis Investigative Site
Toulouse Cedex 9, France, 31000
Germany
Novartis Investigative Site
Berlin, Germany, 10098
Novartis Investigative Site
Essen, Germany, 45122
Novartis Investigative Site
Muenchen, Germany, 80336
Novartis Investigative Site
Würzburg, Germany, 97080
Greece
Novartis Investigative Site
Athens, GR, Greece, 105 52
Novartis Investigative Site
Athens, GR, Greece, 115 27
Israel
Novartis Investigative Site
Heifa, Israel, 35152
Novartis Investigative Site
Jerusalem, Israel, 9112001
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Petach Tikva, Israel, 49100
Italy
Novartis Investigative Site
Ancona, AN, Italy, 60126
Novartis Investigative Site
Cona, FE, Italy, 44100
Novartis Investigative Site
Milano, MI, Italy, 20149
Novartis Investigative Site
Milano, MI, Italy, 20162
Novartis Investigative Site
Padova, PD, Italy, 35128
Novartis Investigative Site
Pisa, PI, Italy, 56124
Novartis Investigative Site
Orbassano, TO, Italy, 10043
Novartis Investigative Site
Torino, TO, Italy, 10126
Novartis Investigative Site
Napoli, Italy, 80131
Mexico
Novartis Investigative Site
México, Distrito Federal, Mexico, 06720
Novartis Investigative Site
México, Distrito Federal, Mexico, 14269
Poland
Novartis Investigative Site
Warszawa, Poland, 01 809
Portugal
Novartis Investigative Site
Porto, Portugal, 4200-319
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Spain, 08041
Turkey
Novartis Investigative Site
Ankara, Turkey, 06100
Novartis Investigative Site
Balcova / Izmir, Turkey, 35340
Novartis Investigative Site
Fatih / Istanbul, Turkey, 34098
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00434148     History of Changes
Other Study ID Numbers: CSOM230B2305, 2006-004111-22
Study First Received: February 9, 2007
Results First Received: January 3, 2013
Last Updated: August 6, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Brazil: National Health Surveillance Agency
Canada: Health Canada
China: Ministry of Health
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: German Institute of Medical Documentation and Information
Greece: National Organization of Medicines
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Spain: Ministry of Health and Consumption
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Cushing's Disease
pasireotide
SOM230

Additional relevant MeSH terms:
Adrenocortical Hyperfunction
Cushing Syndrome
Pituitary ACTH Hypersecretion
Adrenal Gland Diseases
Brain Diseases
Central Nervous System Diseases
Endocrine System Diseases
Hyperpituitarism
Hypothalamic Diseases
Nervous System Diseases
Pituitary Diseases

ClinicalTrials.gov processed this record on August 31, 2015