title: Safety and tolerability of pasireotide long-acting release in acromegaly-results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study.
abstract: OBJECTIVE
  Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734).
  
  
  METHODS
  ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval. Patients received pasireotide long-acting release 40 mg administered intramuscularly every 28 days. The primary outcome was the proportion of patients having a treatment-emergent grade ≥3 or serious adverse event. Efficacy data were not collected.
  
  
  RESULTS
  Forty-four adult patients with active acromegaly were enrolled in the study for an average of 37.6 weeks (range, 4-70 weeks). Twenty-five grade ≥3 treatment-emergent adverse events were reported in 11 patients (25.0 %), 3 of whom (27.3 %) experienced grade ≥3 hyperglycemia. In patients treated with pasireotide long-acting release for ≥3 months (n = 42), mean glycated hemoglobin and fasting plasma glucose levels increased significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at 3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long-acting release for ≥15 months, after which mean glycated hemoglobin and fasting plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients (48 %) initiated antidiabetic medication.
  
  
  CONCLUSIONS
  Grade ≥3 adverse events (primary outcome) were reported in 25.0 % of acromegaly patients treated with pasireotide long-acting release in a clinical setting. Hyperglycemia-related adverse events were reported in 45.5 % of patients, but were typically manageable, supporting the role of pasireotide long-acting release as a safe treatment option for acromegaly patients.
authors.affiliation: Oregon Health & Science University, Portland, OR, USA. fleseriu@ohsu.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Fleseriu
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Elisha
authors.initials: E
authors.lastname: Rusch
authors.affiliation: Division of Endocrinology, Mount Sinai Hospital, New York, NY, USA.
authors.forename: Eliza B
authors.initials: EB
authors.lastname: Geer
mesh_terms: D000172:Acromegaly / Q000188:drug therapy*; D000328:Adult; D001786:Blood Glucose; D003692:Delayed-Action Preparations; D005260:Female; D006728:Hormones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D006728:Hormones; D013004:Somatostatin; C517782:pasireotide
keywords: Acromegaly; Expanded access trial; Fasting plasma glucose; Glycated hemoglobin; Hyperglycemia; Pasireotide LAR