A Randomized, Open-Label, Multicenter, 4-Week Study to Evaluate the Tolerability and Pharmacokinetics of ITCA 650 in Patients With Type 2 Diabetes

Background: Exenatide, a glucagon-like peptide-1 receptor agonist administered by self-injection, decreases plasma glucose, glycosylated hemoglobin (HbA(1c)), and weight in patients with type 2 diabetes. ITCA 650 is an investigational new drug that provides continuous subcutaneous delivery of exenatide. Objective: This randomized, open-label, multicenter, 28-day study evaluated the tolerability, pharmacodynamics, and pharmacokinetics of ITCA 650 in patients with type 2 diabetes. Methods: The study enrolled patients with type 2 diabetes who were receiving a stable regimen of diet and exercise alone or a stable dose of metformin monotherapy, thiazolidinedione monotherapy, or metformin plus thiazolidinedione combination therapy. Patients were randomized to receive 10, 20, 40, or 80 mu g/d of ITCA 650 placed subcutaneously for 28 days. Plasma glucose, HbA(1c), insulin, and weight were measured at regular intervals throughout the study. Exenatide levels and anti-exenatide antibodies were also assessed. Results: Forty-four patients were randomized to treatment. From baseline to end point, significant (P < 0.05) decreases in fasting plasma glucose levels, 2-hour postprandial glucose levels, and glucose AUC curve were seen in all treatment groups. HbA(1c) levels also decreased significantly (P < 0.001) in all 4 treatment groups. Weight was significantly (P < 0.05) lowered in the 40- and 80-mu g/d groups. Detectable levels of exenatide were noted within 12 to 24 hours of ITCA 650 placement, reached steady state by 24 hours, and then remained relatively steady during a plateau period until device removal on day 29. Exenatide levels declined to undetectable levels within 24 hours after removal of the ITCA 650. The most common adverse events were nausea, decreased appetite, and vomiting; these were transient and mostly mild or moderate in severity. Mild local adverse events related to the healing process were common at the placement site but abated after 1 week. Twelve patients developed anti-exenatide antibodies; however, the pharmacokinetics of ITCA 650 were not altered compared with those who did not develop antibodies. Conclusions: ITCA 650 provided continuous and controlled subcutaneous delivery of exenatide for 28 days that was generally well tolerated and produced significant reductions in plasma glucose, HbA(1c), and weight. Further studies are warranted to characterize the long-term tolerability and efficacy of ITCA 650 for the treatment of patients with type 2 diabetes. ClinicalTrials.gov identifier: NCT01798264. (C) 2013 Elsevier HS Journals, Inc. All rights reserved.