title: Evaluation of the Dual-Chamber Pen Design for the Injection of Exenatide Once Weekly for the Treatment of Type 2 Diabetes.
abstract: BACKGROUND
  Exenatide once weekly, an injectable glucagon-like peptide-1 receptor agonist, has been shown to reduce A1C, fasting glucose, and body weight in patients with type 2 diabetes. Exenatide 2.0 mg is dispersed in poly-(D,L-lactide-co-glycolide) polymer microspheres, which require resuspension in aqueous diluent before subcutaneous injection. A single-use, dual-chamber pen was developed to improve the convenience of exenatide once weekly delivery and tested following Food and Drug Administration (FDA) guidance.
  
  
  METHODS
  Design development goals were established, and validation tests (dose accuracy, torque/force requirements, usability, and ease-of-use) were performed. Dose accuracy was tested under a variety of conditions. After 10 exploratory studies in 329 patients, the final design's usability and ease-of-use were tested in untrained health care practitioners (HCPs; n = 16) and untrained/trained patients (n = 30/17). Usability testing evaluated completion of multiple setup, dose preparation, and injection steps. Ease-of-use impression was assessed using a scale of 1-7 (1 = very difficult, 7 = very easy).
  
  
  RESULTS
  The dual-chamber pen successfully met development goals and delivered target volume (650 µL ± 10%) under tested conditions (mean 644.7-649.3 µL), with torque and force requirements below prespecified maximum values. In the final user study, most participants (≥87%) correctly completed pen setup, dose preparation, and injection steps. Mean ease-of-use scores were 5.8, 6.3, and 6.5 out of 7 in untrained HCPs, untrained patients, and trained patients, respectively.
  
  
  CONCLUSIONS
  With self-education or minimal training, participants accurately and precisely suspended, mixed, and delivered exenatide-containing microspheres using the dual-chamber pen with high ease-of-use scores. The dual-chamber pen was FDA-approved in February 2014.
authors.affiliation: AstraZeneca, San Diego, CA, USA susan.larue@astrazeneca.com.
authors.forename: Susan
authors.initials: S
authors.lastname: LaRue
authors.affiliation: Bristol-Myers Squibb, San Diego, CA, USA.
authors.forename: Jaret
authors.initials: J
authors.lastname: Malloy
mesh_terms: D000328:Adult; D018795:Device Approval; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004867:Equipment Design; D000077270:Exenatide; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007279:Injections, Subcutaneous / Q000295:instrumentation*; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D010455:Peptides / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015203:Reproducibility of Results; D012307:Risk Factors; D012646:Self Administration; D013594:Syringes; D019415:Torque; D014481:United States; D014486:United States Food and Drug Administration; D014688:Venoms / Q000008:administration & dosage*
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077270:Exenatide
keywords: GLP-1 analogs; dual-chamber pen; noninsulin injectables; type 2 diabetes