title: Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study.
abstract: OBJECTIVE
  Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease.
  
  
  METHODS
  Phase III study with double-blind randomization of two pasireotide doses.
  
  
  METHODS
  Patients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1·5× upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 μg bid). At month 3, patients with UFC ≤2 × ULN and not exceeding the baseline value continued their randomized dose; all others received 300 μg bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200 μg bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control.
  
  
  RESULTS
  Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72·8% of patients.
  
  
  CONCLUSIONS
  In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased.
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
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: Andrew
authors.initials: A
authors.lastname: Trovato
authors.forename: Gareth
authors.initials: G
authors.lastname: Hughes
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Salgado
authors.forename: André
authors.initials: A
authors.lastname: Lacroix
authors.forename: Jochen
authors.initials: J
authors.lastname: Schopohl
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
mesh_terms: D002784:Cholesterol / Q000097:blood; D003480:Cushing Syndrome / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055105:Waist Circumference / Q000502:physiology
chemical_list: D008077:Lipoproteins, LDL; D013004:Somatostatin; D002784:Cholesterol; C517782:pasireotide