Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease
Condition: Cushing's Disease
MeSH terms: ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion
Intervention: pasireotide LAR; SOM230 LAR 30 mg; SOM230 LAR 10 mg
Intervention description: Pasireotide long-acting was administered as an intra-muscular depot intragluteal injection once every 28 days (±2 days). Patients were administered pasireotide long-acting 10 mg or 30 mg for four months, followed by either continuation of the starting dose, or dose up-titration (if mUFC was still >1.5xULN unless titration was precluded by safety reasons).; starting dose of 30 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of starting dose.; starting does of SOM230 LAR 10 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of the starting dose.
Intervention MeSH terms: Pasireotide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 150.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SOM230; Cushing's Disease; Mean Urinary Free Cortisol; Pasireotide; Pasireotide LAR; Pasireotide long-acting release; secondary hypercortisolism; secondary hypercorticism; Itsenko-Cushing disease; increased secretion of adrenocorticotropic hormone (ACTH); hyperpituitarism

Summary:

      This is a randomized, double-blind, multicenter, phase III study to evaluate the safety and
      efficacy of 2 dosing regiments of Pasireotide long acting release (LAR) in patients with
      Cushing's disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Karnofsky performance status ≥ 60 (i.e. requires occasional assistance, but is able to
             care for most of their personal needs)

          -  For patients on medical treatment for Cushing's disease the following washout periods
             must be completed before screening assessments are performed

               -  Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week

               -  Pituitary directed agents: Dopamine agonists (bromocriptine, cabergoline) and
                  PPARγ agonists (rosiglitazone or pioglitazone): 4 weeks

               -  Octreotide LAR, Lanreotide SR and Lanreotide autogel: 14 weeks

               -  Octreotide (immediate release formulation): 1 week

        Exclusion Criteria:

          -  Patients who are considered candidates for surgical treatment at the time of study
             entry

          -  Patients who have received pituitary irradiation within the last ten years prior to
             visit 1

          -  Patients who have had any previous pasireotide treatment

          -  Patients who have been treated with mitotane during the last 6 months prior to Visit 1

          -  Diabetic patients on antihyperglycemic medications with poor glycemic control as
             evidenced by HbA1c >8%

          -  Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF
             >470 ms, hypokalemia, uncontrolled hypothyroidism, family history of long QT syndrome,
             or concomitant medications known to prolong QT interval

          -  Female patients who are pregnant or lactating, or are of childbearing potential
             (defined as all women physiologically capable of becoming pregnant) and not practicing
             an effective method of contraception/birth control. Sexually active males must use a
             condom during intercourse while taking the drug and for 2 months after the last dose
             of study drug and should not father a child in this period. A condom is required to be
             used also by vasectomized men in order to prevent delivery of the drug via seminal
             fluid