SAN DIEGO – Treatment with the investigational device ITCA 650 delivering exenatide at 20 mcg/day and dose escalation to 60 mcg/day was well tolerated and led to significant reductions in hemoglobin A1c and body weight in patients with type 2 diabetes, results from a phase II, 48-week extension study showed.
ITCA 650 is manufactured by Intarcia Therapeutics of Hayward, Calif., and is a matchstick-size, osmotic mini-pump using the DUROS technology that is placed subcutaneously, providing continuous and consistent delivery of exenatide (Byetta) at specified doses. The device is inserted during a 10- to 15-minute office procedure. ITCA 650 has been shown to be effective in lowering HbA1c and having a favorable weight profile at 12 and 24 weeks, Dr. Julio Rosenstock said at the meeting, where he presented the results of the 48-week extension of the study that demonstrated sustained effects.
“Therefore, this device has the potential for greater adherence using ITCA 650 devices that can deliver 6 or 12 months of treatment with a single placement,” said Dr. Rosenstock, director of the Dallas Diabetes and Endocrine Center at Medical City and the study's principal investigator. “It also may result in enhanced efficacy and a reduced side effect profile.”
In a trial conducted at 50 sites, 155 patients treated with metformin who had baseline HbA1c levels between 7% and 10% were enrolled in a 24-week study and were randomized to receive ITCA 650 at 20, 40, 60, or 80 mcg/day following an initial 12 weeks of either ITCA 650 (20 or 40 mcg/day) or exenatide injections (10 mcg b.i.d. self-injection). At week 24, Dr. Rosenstock and his associates offered patients the option to continue treatment at their current dose for an additional 12 weeks. A total of 86 patients from 35 of the original 50 sites entered the extension study.
Dr. Rosenstock reported that continued reductions in HbA1c and weight were observed across all ITCA 650 treatment arms at week 48, compared with week 24, with the greatest reductions seen in the 60-mcg/day and 80-mcg/day arms. Between baseline and week 48 the mean HbA1c improved 1% in the 20-mcg/day arm (from 7.8% to 6.8%), 1% in the 40-mcg/day arm (from 7.8% to 6.8%), 1.5% in the 60-mcg/day arm (from 8.1% to 6.6%), and 1.4% in the 80-mcg/day arm (from 7.9% to 6.5%). Weight reductions were observed in all treatment arms (mean reductions of 6, 10.8, 7.7, and 7.9 pounds, respectively).
There were no treatment discontinuations between weeks 24 and 48 in the group initially treated with 20 mcg/day and then escalated to 60 mcg/day, Dr. Rosenstock said. The chief side effects in all of the dose groups were nausea (10.5%) and diarrhea (3.5%). Other reported side effects were related to the skin at the placement site and included irritation (7%), pain (7%), erythema (4.7%), pruritus (3.5%), and hematoma (3.5%).
According to a prepared statement from Intarcia, a phase III study planned for 2011 will evaluate treatment regimens involving initial 12-week ITCA dosing at 20 mcg/day transitioning to 60 mcg/day thereafter using ITCA 650 devices of both 6- and 12-month duration.
Dr. Rosenstock has relationships with numerous pharmaceutical and device companies, including Intarcia Therapeutics, in the form of research support, advisory board roles, and consulting honorariums.