ROME, September 9 /PRNewswire/ --
-- FOR EUROPEAN MEDICAL MEDIA ONLY
-- New Data Presented for the First Time at EASD 2008
-- Saxagliptin With Metformin as Initial Combination Therapy Lowered A1C
-- Improvements Demonstrated Across Key Measures of Glucose Control Studied in Treatment-Naïve People With Type 2 Diabetes
-- For Presentation Time and Detailed Study Information Please Refer to Notes to Editors
Results from a 24-week Phase III study presented at the 44th European Association for the Study of Diabetes Annual Meeting demonstrated that saxagliptin, an investigational selective inhibitor with extended binding to the dipeptidyl peptidase-4 (DPP-4) enzyme, in development by Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca, when used in combination with metformin as an initial therapy, produced reductions across all key measures of glucose control studied (glycosylated hemoglobin level (A1C), fasting plasma glucose (FPG) and postprandial glucose (PPG)) in treatment-naïve people with inadequately controlled type 2 diabetes, compared with monotherapy with saxagliptin or metformin. The initial combination of saxagliptin and metformin was well tolerated during the course of the study, and more people were able to achieve target A1C of less than 7 percent, compared with monotherapy with saxagliptin or metformin.
"With these new data, Phase III studies for saxagliptin have demonstrated that saxagliptin improved key markers for glucose control when given with standard therapies for type 2 diabetes and as a monotherapy," said Professor Anthony Barnett, University of Birmingham and Heart of England NHS Foundation Trust. "The clinical trial programme for saxagliptin evaluated more than 5,000 individuals, including more than 4,000 who were given saxagliptin."
The companies submitted a New Drug Application to the U.S. Food & Drug Administration (FDA) on 30th June, which has been officially filed by the FDA, and a Marketing Authorization Applic ation to the European Medicines Agency (EMEA) on 1st July, which has been accepted for review by the Agency. The submissions are based on data from a comprehensive clinical trial programme conducted in addition to standard therapies, as well as in treatment-naïve patients as a monotherapy. The clinical trial programme included studies that evaluated the drug at up to 80 times the proposed usual clinical dose of 5 mg, once daily. The six core Phase III trials assessing the efficacy and safety profile of saxagliptin involved more than 4,000 patients, including 3,000 who were treated with saxagliptin.
Notes to Editors
Study results in detail:
Phase III - Oral Presentation: Initial combination therapy with saxagliptin and metformin improves glycemic control compared with either monotherapy alone in drug-naïve patients with type 2 diabetes
Presentation: 9th September 2008, 10h45 - 12h15 Central European Time (CET)
The study was designed to assess saxagliptin as an initial combination therapy with metformin versus each agent alone. The data represent findings from a 24-week, randomized, double-blind, active-controlled study of 1,306 people with type 2 diabetes (ages 18-77) who were treatment naïve and whose A1C level was greater than or equal to 8 percent and less than or equal to 12 percent. After a one-week placebo lead-in phase, individuals were randomized to one of four separate treatment arms: saxagliptin 5 mg + metformin 500 mg (n=320), saxagliptin 10 mg + metformin 500 mg (n=323), saxagliptin 10 mg + placebo (n=335) or metformin 500 mg + placebo (n=328), given daily. From week 1 to week 5, in the saxagliptin 5 mg + metformin, saxagliptin 10 mg + metformin and metformin + placebo treatment arms, metformin was up-titrated weekly in 500 mg increments, as tolerated, to a maximum total daily dose of 2,000 mg, based on levels of FPG (a measure of a person's blood glucose after at least eight hours of fasting(1)).
The primary endpoint of the study was the change from baseline to week 24 in A1C. The secondary endpoints included the proportion of individuals achieving the American Diabetes Association recommended A1C target of less than 7 percent, the proportion of individuals achieving the International Diabetes Federation recommended A1C target of less than or equal to 6.5 percent and changes from baseline in FPG and PPG (a measure of a person's blood glucose after a meal), measured during an oral glucose tolerance test (OGTT).
Study results
After 24 weeks, individuals in the saxagliptin + metformin treatment arms demonstrated an adjusted mean change in A1C from baseline of -2.5 percent for saxagliptin 5 mg + metformin and -2.5 percent for saxagliptin 10 mg + metformin, compared with -1.7 percent for saxagliptin 10 mg + placebo and -2.0 percent for metformin + placebo (p-value less than 0.0001 for both treatment arms).
A greater percentage of individuals treated with saxagliptin in combination with metformin achieved A1C of less than 7 percent: 60.3 percent for saxagliptin 5 mg + metformin and 59.7 percent for saxagliptin 10 mg + metformin, compared with 32.2 percent for saxagliptin 10 mg + placebo and 41.1 percent for metformin + placebo (p-value less than 0.0001 for both treatment arms). A greater percentage of individuals treated with saxagliptin in combination with metformin also achieved A1C of less than or equal to 6.5 percent: 45.3 percent for saxagliptin 5 mg + metformin and 40.6 percent for saxagliptin 10 mg + metformin, compared with 20.3 percent for saxagliptin 10 mg + placebo and 29.0 percent for metformin + placebo (p-value less than or equal to 0.0026 for both treatment arms).
Individuals treated with saxagliptin in combination with metformin demonstrated an adjusted mean change in FPG from baseline: -60 mg/dL for saxagliptin 5 mg + metformin and -62 mg/dL for saxagliptin 10 mg + metformin, compared with -31 mg/dL for saxagliptin 10 mg + placebo and -47 mg/dL for metformin + placebo (p-value less than or equal to 0.0002 for both treatment arms). The two saxagliptin + metformin treatment arms also demonstrated adjusted mean decreases in PPG from baseline, compared with either monotherapy.
Throughout 24 weeks, the incidence of adverse events was: 55.3 percent for saxagliptin 5 mg + metformin, 57.3 percent for saxagliptin 10 mg + metformin, 53.4 percent for saxagliptin 10 mg + placebo and 58.5 percent for metformin + placebo. The percentages of the most commonly reported (greater than or equal to 5 percent) adverse events for saxagliptin from the saxagliptin 5 mg + metformin, saxagliptin 10 mg + metformin, saxagliptin 10 mg + placebo and metformin + placebo treatment arms, respectively, were: nasopharyngitis (6.9, 2.5, 4.2, 4.0), headache (7.5, 9.9, 6.3, 5.2), diarrhoea (6.9, 9.6, 3.0, 7.3) and hypertension (4.7, 5.3, 4.5, 3.4).
The reported hypoglycemic events were: 3.4 percent for saxagliptin 5 mg + metformin, 5.0 percent for saxagliptin 10 mg + metformin, 1.5 percent for saxagliptin 10 mg + placebo and 4.0 percent for metformin + placebo. The occurrence of confirmed hypoglycemia (symptoms of hypoglycemia with a fingerstick glucose less than or equal to 50 mg/dL) was: two cases (0.6 percent) in the saxagliptin 10 mg + metformin group and one case (0.3 percent) in the metformin + placebo monotherapy group, with no cases of confirmed hypoglycemia in the saxagliptin 5 mg + metformin or the saxagliptin 10 mg + placebo groups.
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