• Diabetes & Endocrinology Clinical Trials
• Diabetes Mellitus

Exenatide therapy in patients with type 2 diabetes who take metformin requires twice-daily self-injections and is associated with significant nausea and vomiting [Pinelli NR, Hurren KM. Ann Pharmacother 2011]. Continuous delivery of exenatide was evaluated in a Phase 2, randomized study with ITCA 650, a subcutaneous osmotic delivery system that provides constant delivery of exenatide at specified doses [ITCA 650; NCT00943917]. Julio Rosenstock, MD, University of Texas Southwestern Medical School, Dallas, Texas, USA, presented findings from the study.

The primary outcome for the 24-week, randomized, multicenter trial was efficacy of specific doses of ITCA 650. Eligibility criteria included males or females aged 18 to 70 years with type 2 diabetes mellitus for ≥6 months prior to Screening Visit 1; a stable (>3 months prior to Screening Visit 1) treatment regimen of metformin monotherapy; fasting plasma glucose <240 mg/dL at Screening Visit 1; and HbA1C ≥7% and ≤10% at Screening Visit 1.

Exclusion criteria included prior treatment with exenatide, TZDs, sulfonylureas, DPP IV inhibitors, acarbose, or insulin (injected or inhaled); history of type 1 diabetes and/or diabetic ketoacidosis; body mass index ≥40 kg/m²; and history of organ transplantation.

Subjects (n=155) were randomized to receive ITCA 650, implanted every 3 months at 20, 40, 60, or 80 mcg/day following 12 weeks of either ITCA 650 (20 or 40 mcg/day) or exenatide injections (10 mcg BID). At Week 12, the completion rate for ITCA 650 was 93% versus 89% for exenatide injections; respective withdrawals due to nausea were 3.9% versus 5.7%.

At Week 24, subjects were offered the option to continue treatment at their current dose for an additional 24 weeks; 85% of eligible subjects elected to continue treatment. During the 6-month extension, HbA1C and body weight reductions were sustained. No subjects withdrew for any reason. One patient reported nausea; none reported vomiting. No cases of hypoglycemia occurred.

Significant reductions in HbA1C (p<0.0001 for all does groups) and weight (p<0.001 for the 40 mcg/day dose and p<0.05 for all other doses) at Week 48 were maintained from those that were initially observed at Week 24. Desirable trends in lipids and blood pressure were also noted. Changes that were seen at 60 mcg/day, the long-term dose that was selected for future studies, were −3.1% for total cholesterol, −9.9% for triglycerides, −5.2% for low-density lipoprotein cholesterol, −1.7 mm Hg for systolic blood pressure, and −7.8 mm Hg for diastolic blood pressure. High-density lipoprotein cholesterol increased by 0.5%. Continuing treatment with ITCA 650 was very well tolerated, with minimal side effects and a completion rate of 85%.

Study delivery technology consisted of sterile, nonbiodegradable, single-use devices for continuous, subcutaneous administration of therapeutic molecules at steady rates. It is capable of delivering a wide range of therapeutic molecules for durations that range from 3 to 12 months [Rohloff CM et al. J Diabetes Sci Technol 2008].

This extension study shows that long-term treatment with ITCA 650 is effective in controlling glycemic parameters and weight and can also lead to potentially positive cardiovascular benefits through beneficial changes in lipids and blood pressure. In addition, tolerability is excellent, with minimal gastrointestinal side effects. Phase 3 studies will evaluate chronic treatment with ITCA 650 using devices of 6 to 12 months in duration.

• © 2011 MD Conference Express