Efficacy and Safety of ITCA 650, a Novel Drug-Device GLP-1 Receptor Agonist, in Type 2 Diabetes Uncontrolled With Oral Antidiabetes Drugs: The FREEDOM-1 Trial

Abstract

OBJECTIVEITCA 650 (exenatide in osmotic mini-pump) continuously delivers exenatide subcutaneously for 3-6 months. Two doses of ITCA 650 were compared with placebo in patients with uncontrolled type 2 diabetes. RESEARCH DESIGN AND METHODSThis 39-week, phase 3, double-blind, placebo-controlled trial randomized 460 patients aged 18-80 years with glycated hemoglobin (HbA 1c ) 7.5-10% [58-86 mmol/mol] 1:1:1 to placebo, ITCA 650 40 mg/day, or ITCA 650 60 mg/day. Primary end point was change in HbA 1c at 39 weeks. was attained in 37%, 44%, and 9% of ITCA 650 40 mg/day, ITCA 650 60 mg/day, and placebo groups, respectively (P < 0.001 each dose vs. placebo). LS mean change from baseline body weight was 22.3 kg and 23.0 kg for ITCA 650 40 and 60 mg/day, respectively (P £ 0.015 vs. placebo 21.0 kg). Nausea was the most common adverse event (AE) and subsided over time. Discontinuation for gastrointestinal AEs occurred in 7.2% with ITCA and 1.3% with placebo. Most AEs associated with procedures to place and remove ITCA 650 were mild and transient. RESULTS Least squares (LS) mean change from baseline CONCLUSIONSITCA 650 significantly reduced HbA 1c and weight compared with placebo and was well tolerated in patients with uncontrolled type 2 diabetes on oral antidiabetes medications.

Incretins in obesity and diabetes

“…Semaglutide has two amino acid substitutions compared to native GLP-1 (Ala 8 by Aib 8 and Lys 34 by Arg 34 ), and similar to liraglutide, is attached at Lys 26 with a longer linker and a longer fatty acid chain of C18 instead of C16. 211 A Phase III open-label trial in type 2 diabetic patients with baseline A1c of 10.8% showed that after 39 weeks of treatment, a reduction of A1c of -2.8% was achieved. 205 The current FDA-approved semaglutide is administered via subcutaneous injection.…”

The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs

“…8,9 In a randomized, open-label, phase 2 study, patients with poorly controlled type 2 diabetes receiving metformin were treated using ITCA 650 delivering 20 lg of exenatide/day for 12 weeks followed by 60 lg/day for 12 weeks. These patients experienced significant reductions in HbA 1c of -1.4% and reductions in body weight of -3.1 kg during the initial 24-week treatment period, and these effects were maintained during a 24-week extension.…”

Itca 650

“…Mean weight losses of 2.3 kg and 3.0 kg were demonstrated in the ITCA 650 arms versus 1.0 kg loss with placebo (p < 0.015). At the end point, 37%, 44% and 9% of patients achieved an HbA 1c of 53 mmol/mol in the 40 μg/day, 60 μg/day and placebo groups, respectively (p < 0.001 versus placebo) …”

“…Two of the phase 3 efficacy and tolerability outcomes have recently been published. The FREEDOM‐1 trial was a double‐blinded randomised placebo controlled trial conducted over a 39‐week period. A total of 460 patients with established type 2 diabetes and HbA 1c between 58–86 mmol/mol were recruited from 126 sites in the USA and were randomised to receive ITCA 650 40 μg/day, ITCA 650 60 μg/day or identically placed mini pumps containing placebo.…”

“…A total of 460 patients with established type 2 diabetes and HbA 1c between 58–86 mmol/mol were recruited from 126 sites in the USA and were randomised to receive ITCA 650 40 μg/day, ITCA 650 60 μg/day or identically placed mini pumps containing placebo. The primary end point evaluated change in HbA 1c at 39 weeks and results demonstrated a statistically and likely clinically significant improvement in glycaemic control, with mean reductions in HbA 1c 12.2 mmol/mol, 13.2 mmol/mol and 1.3 mmol/mol in the ITCA 650 40 μg/day, ITCA 650 60 μg/day and placebo groups, respectively (p = 0.001 versus placebo) . Pre‐defined secondary end points were also examined.…”