Additional Findings Reported Safety & Tolerability Profile in Subjects with Type 2 Diabetes and Healthy Subjects
CHICAGO, June 25 /PRNewswire-FirstCall/ -- Phase III data presented this week at the annual meeting of the American Diabetes Association demonstrated that 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 was the first time that Phase III data for saxagliptin have been presented in a scientific setting.
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
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%.
Phase I Studies Also Presented at 2007 American Diabetes Association Annual Meeting
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,
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.
Study 1 consisted of 40 subjects (ages 18-70) who had been diagnosed with Type 2 diabetes for less than 10 years, had hemoglobin A1C in the range of 6.5 to 9.5 percent, and fasting plasma glucose in the range 125-250 mg/dL. Participants were randomized to receiv e 2.5, 5, 15, 30, or 50 mg of saxagliptin or matched placebo once-daily for 14 days (3 saxagliptin, 1 placebo ratio, n=8 subjects/dose panel).
Study 2 consisted of 50 healthy subjects (ages 18-45) who were randomized to receive 40, 100, 150, 200, 300 or 400 mg saxagliptin or matching placebo once daily for 14 days. Within each panel, 6 subjects received 100, 150, 200, 300 or 400 mg saxagliptin, 2 subjects received 40 mg saxagliptin and 2 subjects received matching placebo.
In both studies, there were no deaths or serious adverse events. Additionally, no adverse events of hypoglycemia were reported by investigators. In Study 2, one participant experienced an adverse event (mild rash), which resulted in discontinuation from the study while taking 200 mg of saxagliptin once daily.
About Type 2 Diabetes
Type 2 diabetes is the most common form of diabetes, accounting for approximately 90-95 percent of diabetes cases. Having Type 2 diabetes increases the risk of many serious complications, including heart disease or stroke, high blood pressure, amputation (particularly legs), blindness, nerve damage, and kidney failure. The risk of stroke and the rate of deaths due to heart disease are two to four times higher among people with diabetes, and about 65 percent of deaths among people with diabetes are due to heart disease and stroke.
The A1C test (also known as hemoglobin A1C) is used primarily to monitor the glucose control of diabetics over time. The goal of those with diabetes is to keep their blood glucose levels as close to normal as possible. This helps to minimize the complications caused by chronically elevated glucose levels, such as progressive damage to body organs like the kidneys, eyes, cardiovascular system, and nerves. The A1C test gives a picture of the average amount of glucose in the blood over the last few months. It can help a patient and his doctor know if the measures they are taking to control the pa tient's diabetes are successful or need to be adjusted.
Saxagliptin is an investigational drug under development by Bristol-Myers Squibb and AstraZeneca. It is being studied as a once daily antidiabetic in the class of dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of Type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver.
Bristol-Myers Squibb and AstraZeneca Partnership
In January 2007, Bristol-Myers Squibb and AstraZeneca entered into a collaboration to develop and commercialize saxagliptin and dapagliflozin, two compounds under investigation by Bristol-Myers Squibb for the treatment of diabetes. Both companies will jointly set development and commercial strategy for the two compounds. AstraZeneca will provide funding for the majority of currently planned development activities; additional development activity will be funded equally.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical and related healthcare products company whose mission is to extend and enhance human life.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the development and commercialization of products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looki ng statement can be guaranteed. Among other risks, there can be no guarantee that the development of the products described in this release will be successful, that the products described in this release will receive regulatory approval, or that if approved, will be commercially successful. Forward-looking statements in the press release should be evaluated together with the many uncertainties that affect Bristol- Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2006, its Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
In the United States, AstraZeneca is a $12.44 billion healthcare business with more than 12,000 employees. For nearly three decades, AstraZeneca has offered drug assistance programs side by side with its medicines, and over the past five years, has provided over $3 billion in savings to more than 1 million patients throughout the US and Puerto Rico. AstraZeneca has been named one of the "100 Best Companies for Working Mothers" by Working Mother magazine and is the only large pharmaceutical company named to FORTUNE magazine's 2007 list of "100 Best Companies to Work For." In 2006, for the fifth consecutive year, Science magazine named AstraZeneca a "Top Employer" on its ranking of the world's most respected biopharmaceutical employers.
AstraZeneca Forward-Looking Statement
The statements herein include forward-looking statements. By their nature, forward-looking statements and forecasts involve risk and uncertainty. For a discussion of those risks and uncertainties please see the company's Annual Report/Form 20-F for 2006.
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