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

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.

Twenty four hour urine samples were collected to obtain mUFC measurements. A negative change from baseline indicates improvement.

Time to first UFC response is defined as the number of months from baseline to first attainment of UFC response.

Blood samlpes were drawn to obtain serum cortisol levels. A negative change from baseline indicates improvement.

Blood samples were drawn to obtain ACTH levels. A negative change from baseline indicates improvement.

Sitting blood pressure assessments were performed at every study visit. A negative change from baseline indicates improvement.

BMI was determined by using height and weight measurements. A negative change from baseline indicates improvement.

Waist circumference was measured with a measuring tape correctly positioned. A negative change from baseline indicates improvement.

Blood samples were drawn to obtain total cholesterol and triglycerides' levels. A negative change from baseline indicates improvement.

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.

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.

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.

Body composition as in percentage of body fat by region was assessed by total body scan. A negative change from baseline indicates improvement.

Pituitary magnetic resonance imaging (MRI) was performed to determine tumor volume. A negative change from baseline indicates imrpovement.

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.