Saxagliptin, an inhibitor of dipeptidyl-peptidase-4 (DPP-4) in development by Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN), in combination with metformin, exhibited a statistically significant improvement in glycemic control in subjects with Type 2 diabetes compared to metformin alone through 24 weeks of treatment.
This Phase III data for saxagliptin have been presented in a scientific setting first time at the annual meeting of the American Diabetes Association.
A group of 743 subjects (ages 18-77) with Type 2 diabetes whose hemoglobin A1C level was within the range of greater than or equal to 7 percent or less than or equal to 10 percent and on a stable metformin dose alone (1500 to 2550 mg/day) were randomized 1:1:1:1 to add-on saxagliptin 2.5 mg, 5 mg, 10 mg, or placebo once daily. The primary endpoint of the study was the change from baseline in hemoglobin A1C levels. After 24 weeks, the subjects receiving saxagliptin+metformin demonstrated statistically significant decreases in hemoglobin A1C levels compared to placebo+metformin: -0.73 percent, -0.83 percent, and -0.72 percent at the 2.5 mg, 5 mg and 10 mg doses, respectively (p-value at all dosage levels less than 0.0001 vs. placebo+metformin).
Saxagliptin+metformin also statistically significantly reduced fasting plasma glucose (secondary endpoint) as compared to placebo+metformin: -16 mg/dL, -23 mg/dL, and -22 mg/dL for saxagliptin 2.5 mg, 5 mg and 10 mg, respectively (p-value at all dosage levels less than 0.0001 vs. placebo+metformin). The percentage of subjects with hemoglobin A1C less than 7 percent at Week 24 (secondary endpoint) was 17 percent for placebo+metformin and 37 percent, 44 percent and 44 percent for the 2.5 mg, 5 mg and 10 mg doses of saxagliptin respectively (p-value at all dosage levels less than 0.0001 vs. placebo+metformin).
In this study, the number of subjects with investigator-reported hypoglycemia, with or without confirmation, were: 9 on placebo+metformin, and 15, 10 and 7, for 2.5 mg, 5 mg, and 10 mg on saxagliptin+metformin, respectively. There was one subject with confirmed hypoglycemia in each of the four arms (as measured by blood glucose less than or equal to 50 mg/dL with symptoms). The most common adverse events seen in more than 5 percent of subjects randomized to either placebo+metformin or saxagliptin+metformin (all doses combined) were: nasopharyngitis 7.8% vs. 8.7 %, headache 7.3% vs. 8.0%, diarrhea 11.2% vs. 7.1%, upper respiratory infection 5.0% vs. 6.6%, influenza 7.3% vs. 6.0%, and urinary tract infection 4.5% vs. 5.1%.
In the presentation “Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Once-Daily Oral Doses of Saxagliptin for 2 Weeks in Type 2 diabetic and Healthy Subjects” by David Boulton, Ph.D., Principal Scientist, Bristol-Myers Squibb, results from two Phase I studies were reported. Study 1 was conducted in subjects with Type 2 diabetes; Study 2 was conducted in healthy subjects. Both studies were placebo-controlled, randomized, double-blind, sequential, multiple ascending dose studies. The primary objective of these two studies was to assess the safety and tolerability profiles of multiple daily oral doses of saxagliptin in subjects with Type 2 diabetes and in healthy subjects.