Evaluation of the Dual-Chamber Pen Design for the Injection of Exenatide Once Weekly for the Treatment of Type 2 Diabetes

Abstract

Exenatide is the first-in-class glucagon-like peptide-1 receptor agonist (GLP-1RA) originally approved in 2005 by the US Food and Drug Administration (FDA) as a twice daily premeal subcutaneous injection administered by pen for the treatment of hyperglycemia in patients with type 2 diabetes mellitus (T2DM).1 GLP-1RAs increase glucose-dependent insulin secretion, suppress glucagon secretion, and slow gastric emptying.2 The exenatide molecule shares approximately 53% structural similarity to human GLP-1 but is resistant to enzymatic degradation by dipeptidyl peptidase-4 resulting in a prolonged physiological response and an increased halflife of 2.4 hours compared with 2 minutes for native GLP-1. [1][2][3] In 2012, the US FDA approved a long-acting formulation of exenatide for once-weekly administration that can be administered regardless of meal times; 4 European Medicines Agency approval occurred in 2011. The long-acting, sustained release of exenatide is achieved by dispersion of the parent exenatide molecule in poly-(D,L-lactide-co-glycolide) polymer microspheres approximately 0.06 mm in diameter. Similar polymer material has been used in surgical sutures, bone plates, and orthopedic implants for decades. 5These exenatide-containing microspheres must be suspended 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.

Efficacy and safety of autoinjected exenatide once‐weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: The DURATION‐NEO‐2 randomized clinical study

“…A once‐weekly (QW) formulation was later developed, containing the active ingredient of exenatide BID encapsulated into biodegradable poly( d , l ‐lactide‐coglycolide) microspheres . Exenatide QW is administered using a single‐dose tray, with some assembly required, or as a pre‐assembled single‐dose dual‐chamber pen . For both devices, patients need to mix exenatide‐containing microspheres and aqueous diluent before injection …”

“…Exenatide QW is administered using a single‐dose tray, with some assembly required, or as a pre‐assembled single‐dose dual‐chamber pen . For both devices, patients need to mix exenatide‐containing microspheres and aqueous diluent before injection …”

“…5 Exenatide QW is administered using a single-dose tray, with some assembly required, 6 or as a pre-assembled single-dose dual-chamber pen. 7 For both devices, patients need to mix exenatide-containing microspheres and aqueous diluent before injection. 4,7 Exenatide delivery has been further simplified by the development of a QW suspension for autoinjection (QWS-AI), in which the microspheres are suspended in a mixture of nonaqueous triglycerides (Miglyol 812).…”

Mixing Pens and the Future of Diabetes Drugs

“…This interesting article 1 raises points in three very interesting areas of diabetes technology: (1) Can we use technology to reduce the burden of taking medications? (2) How is this type of device evaluated by the FDA?…”

“…11 As new biologics develop, proteins, polypeptides, and polynucleotides, some will be less stable and we can expect to see a variety of devices, some with new diabetes medications. 12 Highquality, easy-to-use devices, such as the one described in the LaRue and Malloy article, 1 will be important for appropriate therapy.…”