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: February 5, 2016
Last verified: February 2016

February 9, 2007
February 5, 2016
December 2006
March 2010   (final data collection date for primary outcome measure)
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.
Efficacy assessed by urinary free cortisol levels after 6 months of treatment
Complete list of historical versions of study NCT00434148 on ClinicalTrials.gov Archive Site
  • 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.
  • Efficacy assessed by serum cortisol levels
  • Patient Quality of Life assessed by questionnaire
  • Efficacy assessed by clinical signs and symptoms of Cushing's Disease
  • Pharmacokinetics
  • Efficacy assessed by tumor size
Not Provided
Not Provided
 
Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing's Disease
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
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Cushing's Disease
Drug: Pasireotide
  • 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.
    Intervention: 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.
    Intervention: Drug: Pasireotide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
162
May 2014
March 2010   (final data collection date for primary outcome measure)

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.

Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Belgium,   Brazil,   Canada,   China,   Denmark,   Finland,   France,   Germany,   Greece,   Israel,   Italy,   Mexico,   Poland,   Portugal,   Spain,   Turkey
 
NCT00434148
CSOM230B2305, 2006-004111-22
No
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP