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-coglycolide) 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 easeof-use scores were 5.8, 6.3, and 6.5 out of 7 in untrained HCPs, untrained patients, and trained patients, respectively. Conclusion: 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.