title: A 12-month phase 3 study of pasireotide in Cushing's disease.
abstract: BACKGROUND
  Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5.
  
  
  METHODS
  In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 μg (82 patients) or 900 μg (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 μg twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12.
  
  
  RESULTS
  Twelve of the 82 patients in the 600-μg group and 21 of the 80 patients in the 900-μg group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients.
  
  
  CONCLUSIONS
  The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, Section of Endocrinology, University of Naples Federico II, Naples, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Stephan
authors.initials: S
authors.lastname: Petersenn
authors.forename: John
authors.initials: J
authors.lastname: Newell-Price
authors.forename: James W
authors.initials: JW
authors.lastname: Findling
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Mario
authors.initials: M
authors.lastname: Maldonado
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schoenherr
authors.forename: David
authors.initials: D
authors.lastname: Mills
authors.forename: Luiz Roberto
authors.initials: LR
authors.lastname: Salgado
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood / Q000652:urine*; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D012008:Recurrence; D012463:Saliva / Q000737:chemistry; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; C517782:pasireotide; D006854:Hydrocortisone