-- Additional Findings Reported on Glucose Homeostasis Effects in Normal
and Diabetic Rats --
CHICAGO, June 25 /PRNewswire-FirstCall/ -- In a 14-day, Phase IIa study
of the safety profile of multiple doses of the investigational compound
dapagliflozin, a selective inhibitor of the Sodium-Glucose Transporter 2
(SGLT2) administered alone or concomitantly with metformin in subjects with
Type 2 diabetes, no discontinuations due to adverse events and no serious
adverse events were reported. The study, presented this week at the annual
meeting of the American Diabetes Association, also reported that
dapagliflozin, in development by Bristol-Myers Squibb Company (NYSE: BMY)
and AstraZeneca (NYSE: AZN), statistically significantly reduced fasting
serum glucose (FSG) and post challenge glucose excursion in subjects with
Type 2 diabetes.
The data were from a double-blind, placebo-controlled, randomized,
parallel-group study of 47 subjects with an established diagnosis of Type 2
diabetes (ages 18-77) who were either drug-naive or on a stable dose of
metformin for at least 4 weeks prior to randomization with hemoglobin A1C
levels between 6 and 10 percent with a FSG of less than or equal to 240
mg/dL. Subjects were randomized to receive either placebo (n=8) or
dapagliflozin 5 mg (n=11), 25 mg (n=12), or 100 mg (n=16) once daily for 14
days in addition to their stable metformin dose and/or diet alone in an
in-patient clinical research unit. The primary endpoint of the study was to
assess both the safety and tolerability profiles of multiple doses of
dapagliflozin in subjects with Type 2 diabetes. The secondary endpoints of
the study included assessing the fasting serum glucose and post challenge
glucose excursion. The presentation, "Dapagliflozin, a Selective Inhibitor
of the Sodium-Glucose Uptake Transporter 2 (SGLT2), Reduces Fasting Serum
Glucose and Glucose Excursion in Type 2 Diabetes Mellitus Patients Over 14
Days", was presented by Bernard Komoroski, PharmD, Ph.D., Senior Research
Investigator, Bristol-Myers Squibb.
On Day 13, the FSG was significantly reduced in participants receiving
dapagliflozin with or without metformin as compared to their FSG levels two
days prior to first dose: -14.5 percent (p-value less than 0.05), -17.3
percent (p-value less than 0.05), -21.9 percent (p-value less than 0.001)
for dapagliflozin at 5 mg, 25 mg and 100 mg, respectively. FSG was reduced
by -6.3 percent in participants receiving placebo with or without
metformin.
There were no discontinuations due to adverse events and no serious
adverse events were reported. Adverse events included two events of
hypoglycemia in subjects receiving dapagliflozin co-administered with
metformin. There were two events of vulvovaginal infection in the study
(one subject receiving dapagliflozin alone and one subject receiving
dapagliflozin+metformin). Adverse events occurred with similar frequency in
subjects receiving dapagliflozin or placebo. The most frequently reported
adverse events were: constipation (n=7; 1/19 on dapagliflozin+metformin,
3/20 on dapagliflozin alone, 2/6 on placebo+metformin, 1/2 on placebo
alone), nausea (n=5; 4/19 on dapagliflozin+metformin, 1/6 on
placebo+metformin), and diarrhea (n=4; 3/19 on dapagliflozin+metformin, 1/6
on placebo+metformin).
Preclinical Data Also Presented at 2007 American Diabetes Association
Annual Meeting
In a second presentation this week - "Dapagliflozin, A Selective SGLT2
Inhibitor, Improves Glucose Homeostasis in Normal and Diabetic Rats" by
Jean Whaley, Sc.D., Director, Diabetes Drug Discovery, Bristol-Myers
Squibb, the effect of dapagliflozin on glucose homeostasis in normal and
diabetic rats was reported. In diabetic rats, dapagliflozin acutely induced
renal glucose excretion at doses ranging from 0.01-1.0 mg/kg of body weight
without inducing hypoglycemia. Additionally, as early as two hours after a
single oral dose, there was a statistically significant reduction in plasma
glucose levels in diabetic rats treated with dapagliflozin compared to
untreated diabetic rats at doses of 0.1 mg/kg and 1.0 mg/kg (-101 mg/dL and
-128 mg/dL), respectively (p-value less than 0.0001 at both doses).
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 patient's diabetes are successful or need to be
adjusted.
About Dapagliflozin
Dapagliflozin (previously referred to as BMS-512148) is an
investigational drug under development by Bristol-Myers Squibb and
AstraZeneca. It is being studied as a once-daily oral antidiabetic. The
compound has a novel proposed mechanism of action, selectively inhibiting
sodium glucose cotransporter 2 (SGLT2) versus SGLT1, decreasing
reabsorption of glucose by the kidneys without affecting SGLT1 in the GI
tract. Dapagliflozin has a C-glucoside chemical structure, which prolongs
the pharmacokinetic half-life and duration of action. Dapagliflozin is
currently in Phase IIb development.
About SGLT2 Inhibitors
Glucose is normally filtered by the kidney, but nearly all of it is
reabsorbed in the proximal tubule by SGLT2, which is located almost
exclusively in the kidney. For patients with diabetes, retention of excess
glucose by this pathway contributes to persistent high blood glucose
levels, or hyperglycemia. Inhibiting SGLT2 activity modulates reabsorption
of glucose in the kidney, resulting in excretion of glucose in the urine.
Research, in animal models, indicates that modulation of renal glucose
absorption with SGLT2 inhibition reduces blood glucose independent of
insulin secretion or action.
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-looking
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.
About AstraZeneca
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.
For more information about Bristol-Myers Squibb, please visit:
http://www.bms.com.
For more information about AstraZeneca, please visit:
http://www.astrazeneca-us.com.
SOURCE Bristol-Myers Squibb; AstraZeneca
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Related links:
http://www.bms.com
http://www.astrazeneca-us.com/
CONTACT:
Media, David M. Rosen of Bristol-Myers Squibb
+1-609-252-5675 or (pager) +1-866-308-4484,
david.m.rosen@bms.com, or David Albaugh of AstraZeneca,
+1-302-886-7098 or (cell) +1-609-304-3445,
david.albaugh@astrazeneca.com; Investors, John Elicker of
Bristol-Myers Squibb, +1-212-546-3775, john.elicker@bms.com, or
Mina Blair of AstraZeneca, +44-20-7304-5084,
mina.blair@astrazeneca.com
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