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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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, Persiste

Brief Summary: 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.

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group [ Time Frame: 6 months ]

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.


Original Primary Outcome: Efficacy assessed by urinary free cortisol levels after 6 months of treatment

Current Secondary Outcome:

  • Change From Baseline in mUFC [ Time Frame: baseline, 3 months, 12 months ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]

    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 ]
    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 ]
    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 ]
    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

    Original Secondary Outcome:

    • 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


    Information By: Novartis

    Dates:
    Date Received: February 9, 2007
    Date Started: December 2006
    Date Completion:
    Last Updated: February 5, 2016
    Last Verified: February 2016