Phase 2b clinical trial data of SGLT2 inhibitor in patients with type 2 diabetes presented at ADA 2010

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) announced today that canagliflozin, an investigational, oral, selective sodium-glucose transporter-2 (SGLT2) inhibitor, improved glycemic control, and was also associated with a decrease in body weight, in a Phase 2b dose-ranging trial in patients diagnosed with type 2 diabetes who were concurrently treated with metformin. The data were presented at the 70th American Diabetes Association (ADA) Scientific Sessions.

Canagliflozin is a member of a new class of antihyperglycemic therapies under development to treat type 2 diabetes. Blood glucose filtered in the kidney is mainly reabsorbed into the blood stream by SGLT2. Inhibiting SGLT2 is believed to reduce blood glucose levels by increasing the amount of glucose excreted in the urine, which may also lead to a loss of calories.

"Most people with type 2 diabetes require treatment with combinations of drugs from multiple classes to attain and sustain good glycemic control," said lead investigator Julio Rosenstock, M.D., Director of the Dallas Diabetes and Endocrine Center at Medical City and also a clinical professor of medicine at the University of Texas Southwestern Medical School. "Our study suggests that inhibiting SGLT2 with canagliflozin in combination with metformin could potentially offer a good alternative for treating patients with type 2 diabetes who are not reaching their goals with metformin alone. These are promising data that need to be confirmed in long-term trials, and I am looking forward to reviewing the results from those ongoing studies."

In this 12-week Phase 2b dose-ranging study of 451 patients with type 2 diabetes concurrently receiving the oral antidiabetic drug metformin, canagliflozin was administered at once-daily doses of either 50, 100, 200 or 300 mg, or 300 mg twice a day. Patients randomized to these arms had observed mean A1C reductions from baseline of 0.8, 0.8, 0.7, 0.9 and 0.9 percent, respectively. A group randomized to receive a once-daily 100 mg dose of another oral antidiabetic, sitagliptin, in an active reference arm had observed mean A1C reductions of 0.7 percent from baseline. In subjects randomized to placebo, A1C decreased by 0.2 percent. Body weight, a key secondary endpoint, decreased from baseline in patients receiving canagliflozin by 2.3 to 3.4 percent compared to a 1.1 percent weight loss in subjects in the placebo arm. Patients on sitagliptin lost 0.6 percent of body weight from baseline. The study was not powered to compare efficacy between canagliflozin and sitagliptin.

In general, adverse events were mild to moderate and the overall incidence was balanced across all arms of the study. Similar incidences of serious adverse events and discontinuations due to adverse events across treatment arms were observed. A non-dose-dependent increase in vulvovaginal candidal infections was seen in subjects receiving canagliflozin. The incidence of hypoglycemic events was low and similar in the canagliflozin and placebo treatment groups. No safety signals in laboratory studies, electrocardiogram or vital signs were observed.

"We are encouraged by these results and by the initiation of our Phase 3 program, which includes a large, prospective study assessing cardiovascular outcomes," said Martin Fitchet, M.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, J&JPRD. "The size and scope of our canagliflozin late-stage development program also reflects our commitment to build a leading portfolio of pharmaceutical treatments for the care of people with diabetes."

Recruitment for the global Phase 3 canagliflozin clinical program is currently underway, and is expected to enroll more than 10,000 patients with type 2 diabetes. The trials are being conducted to assess the safety and efficacy of canagliflozin dosed at 100 or 300 mg as monotherapy and in combination with oral antihyperglycemic agents and/or insulin. The Phase 3 program also includes CANVAS (CANagliflozin cardioVascular Assessment Study), a prospective Phase 3 study to evaluate the safety and glycemic efficacy in approximately 4,500 patients with type 2 diabetes, who also have either a history of, or high risk of cardiovascular disease. Study overviews are available at http://www.clinicaltrials.gov.