Orlando, Florida, June 26, 2010 (ots/PRNewswire) - Bristol-Myers Squibb
Company and AstraZeneca today announced results from a 52-week
Phase 3b study in adults with type 2 diabetes who had inadequate
glycemic control on metformin therapy plus diet and exercise. This
study found that the addition of ONGLYZA(TM) (saxagliptin) 5 mg to
existing metformin therapy achieved the primary objective of
demonstrating non-inferiority compared to the addition of titrated
glipizide (sulfonylurea) to existing metformin therapy in reducing
glycosylated hemoglobin levels (HbA1c). Glipizide 5 mg was titrated
as required to 20 mg (mean dose 14.7 mg). The final dose in
two-thirds of glipizide-treated patients was 15 mg or greater,
requiring two or more dosage titrations. Additionally, the study
found that treatment with ONGLYZA 5 mg plus metformin resulted in a
statistically significant lower proportion of subjects reporting
hypoglycemic events and statistically significant weight loss
compared to titrated glipizide plus metformin. ONGLYZA 5 mg plus
metformin also resulted in a significantly smaller rise per week in
HbA1c from week 24 to week 52 compared to titrated glipizide plus
metformin. Overall adverse events excluding hypoglycemia were
reported at a similar rate between the two treatment groups. Results
were presented at the 70th American Diabetes Association (ADA) Annual
"Many adult patients with type 2 diabetes need more than one
therapy to help improve glycemic control, and the data presented
today adds to the body of evidence for ONGLYZA," said Burkhard Göke,
MD, Professor of Internal Medicine, University Hospital Munich,
ONGLYZA has been submitted for regulatory review in more than 58
countries and is approved in 43 countries, including the United
States, Canada, Mexico, 30 EU countries, Chile, India, Brazil,
Argentina and Switzerland. ONGLYZA was approved by the FDA in July
2009 and is indicated as an adjunct to diet and exercise to improve
blood sugar (glycemic) control in adults for the treatment of type 2
diabetes mellitus. ONGLYZA once daily can be used in combination with
commonly prescribed oral anti-diabetic medications - metformin,
glyburide (a sulfonylurea) or a thiazolidinedione (TZD) (pioglitazone
or rosiglitazone), - or as a monotherapy to significantly reduce
HbA1c levels. ONGLYZA (saxagliptin) should not be used for the
treatment of type 1 diabetes or for the treatment of diabetic
ketoacidosis (high levels of certain acids, known as ketones, in the
blood or urine). ONGLYZA has not been studied in combination with
About The Study: Saxagliptin Added to Metformin vs. Titrated
Glipizide Added to Metformin
The study was a 52-week, international, multicenter, randomized,
parallel-group, double-blind, active-controlled Phase 3b study of 858
patients with type 2 diabetes (aged greater than or equal to 18)
whose HbA1c was greater than 6.5% and less than or equal to 10% at
baseline. The study was designed to assess the efficacy and safety
of ONGLYZA 5 mg per day compared to glipizide 5 mg, titrated as
required to 20 mg as added to a stable dose of metformin (greater
than or equal to 1,500 mg per day) in adult patients with type 2
diabetes who did not achieve adequate glycemic control with
metformin alone. Individuals were randomized to one of two treatment
groups: ONGLYZA 5 mg once daily plus metformin (n=428) or glipizide 5
mg (titrated as required to 20 mg) plus metformin (n=430).
The primary endpoint of the study was to assess whether the
change from baseline in HbA1c achieved with ONGLYZA 5 mg was
non-inferior to titrated glipizide (defined in the study protocol as
a treatment group numerical difference in the HbA1c reduction of less
than 0.35% for the upper limit of the two-sided 95% confidence
interval [CI]) when both were added to a stable dose of metformin.
Key secondary endpoints included the proportion of patients reporting
at least one episode of a hypoglycemic event at week 52, change from
baseline in body weight at week 52 and durability of HbA1c effect
based on change per week in HbA1c from week 24 to week 52.
The mean dose of titrated glipizide was 14.7 mg and the median
dose 20 mg. Using the per-protocol analysis, after 52 weeks,
individuals taking ONGLYZA 5 mg plus metformin achieved an adjusted
mean change from baseline in HbA1c of -0.74%, compared to -0.80% for
titrated glipizide plus metformin. Results of the study demonstrated
that therapy with ONGLYZA 5 mg was non-inferior to titrated glipizide
when added to existing metformin therapy (difference in adjusted mean
change from baseline vs. titrated glipizide as added to existing
metformin therapy was 0.06%, 95% CI -0.05 to 0.16). Non-inferiority
of ONGLYZA (saxagliptin) 5 mg to titrated glipizide was also
demonstrated in a confirmatory analysis of all individuals receiving
study treatment for whom HbA1c data were available.
The number of individuals with any hypoglycemic event was
significantly lower for patients treated with ONGLYZA 5 mg plus
metformin as compared to those treated with titrated glipizide plus
metformin (3% for ONGLYZA plus metformin vs. 36.3% for titrated
glipizide plus metformin; p-value less than 0.0001) at week 52.
The study also demonstrated that patients treated with ONGLYZA 5
mg plus metformin experienced a statistically significant weight
decrease when compared to those treated with titrated glipizide plus
metformin (-1.1 kg for ONGLYZA 5 mg plus metformin vs. +1.1 kg for
titrated glipizide plus metformin; p-value less than 0.0001) at week
While both treatment groups exhibited slight increases in HbA1c
from week 24 to week 52, the study demonstrated that patients treated
with ONGLYZA had a smaller rise per week in HbA1c compared to those
treated with titrated glipizide (0.001% for ONGLYZA plus metformin
vs. 0.004% for titrated glipizide plus metformin; p-value equal to
0.04) at week 52.
The number of individuals experiencing adverse events or serious
adverse events after 52 weeks between the two treatment groups were
as follows (excluding hypoglycemia): adverse events: 60.0% for
ONGLYZA 5 mg plus metformin, 56.7% for titrated glipizide plus
metformin; serious adverse events: 9.1% for ONGLYZA 5 mg plus
metformin, 7.4% for titrated glipizide plus metformin. The most
common adverse events (greater than or equal to 5% and observed more
frequently in the ONGLYZA 5 mg treatment group compared to the
titrated glipizide treatment group) were nasopharyngitis (9.6% vs.
8.6%, respectively) and diarrhea (5.1% vs. 3.7%, respectively).
Discontinuations due to adverse events were 4.2% for ONGLYZA 5 mg
plus metformin groups vs. 4.4% for titrated glipizide plus metformin.
IMPORTANT INFORMATION ABOUT ONGLYZA
Indication and Important Limitations of Use
ONGLYZA (saxagliptin) is indicated as an adjunct to diet and
exercise to improve glycemic control in adults with type 2 diabetes
ONGLYZA should not be used for the treatment of type 1 diabetes
mellitus or diabetic ketoacidosis.
ONGLYZA has not been studied in combination with insulin.
Important Safety Information
@@start.t1@@ - Use with Medications Known to Cause Hypoglycemia: Insulin
secretagogues, such as sulfonylureas, cause hypoglycemia. Therefore, a
lower dose of the insulin secretagogue may be required to reduce the
risk of hypoglycemia when used in combination with ONGLYZA.
- Macrovascular Outcomes: There have been no clinical studies
establishing conclusive evidence of macrovascular risk reduction with
ONGLYZA or any other antidiabetic drug.@@end@@
Most common adverse reactions (regardless of investigator
assessment of causality) reported in greater than or equal to 5% of
patients treated with ONGLYZA and more commonly than in patients
treated with control were upper respiratory tract infection (7.7%,
7.6%), headache (7.5%, 5.2%), nasopharyngitis (6.9%, 4.0%) and
urinary tract infection (6.8%, 6.1%). When used as add-on combination
therapy with a thiazolidinedione, the incidence of peripheral edema
for ONGLYZA 2.5 mg, 5 mg, and placebo was 3.1%, 8.1% and 4.3%,
Laboratory Tests: There was a dose-related mean decrease in
absolute lymphocyte count observed with ONGLYZA.
Drug Interactions: Because ketoconazole, a strong CYP3A4/5
inhibitor, increased saxagliptin exposure, the dose of ONGLYZA should
be limited to 2.5 mg when coadministered with a strong CYP3A4/5
inhibitor (e.g., atazanavir, clarithromycin, indinavir, itraconazole,
ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and
Patients with Renal Impairment: The dose of ONGLYZA (saxagliptin)
is 2.5 mg once daily for patients with moderate or severe renal
impairment, or with end-stage renal disease requiring hemodialysis
(creatinine clearance [CrCl] less than or equal to 50 mL/min).
ONGLYZA should be administered following hemodialysis. ONGLYZA has
not been studied in patients undergoing peritoneal dialysis.
Assessment of renal function is recommended prior to initiation of
ONGLYZA and periodically thereafter.
Pregnant and Nursing Women: There are no adequate and
well-controlled studies in pregnant women. ONGLYZA, like other
antidiabetic medications, should be used during pregnancy only if
clearly needed. It is not known whether saxagliptin is secreted in
human milk. Because many drugs are secreted in human milk, caution
should be exercised when ONGLYZA is administered to a nursing woman.
Pediatric Patients: Safety and effectiveness of ONGLYZA in
pediatric patients have not been established.
U.S. Full Prescribing Information is available at
Bristol-Myers Squibb and AstraZeneca Collaboration
Bristol-Myers Squibb and AstraZeneca entered into a collaboration
in January 2007 to enable the companies to research, develop and
commercialize select investigational drugs for type 2 diabetes. The
Bristol-Myers Squibb/AstraZeneca Diabetes collaboration is dedicated
to global patient care, improving patient outcomes and creating a new
vision for the treatment of type 2 diabetes.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines that
help patients prevail over serious diseases. For more information
about Bristol-Myers Squibb, visit www.bms.com or follow us on Twitter
AstraZeneca is a global, innovation-driven biopharmaceutical
business with a primary focus on the discovery, development and
commercialization of prescription medicines. As a leader in
gastrointestinal, cardiovascular, neuroscience, respiratory and
inflammation, oncology and infectious disease medicines, AstraZeneca
generated global revenues of $32.8 billion in 2009. In the United
States, AstraZeneca is a $14.8 billion healthcare business.
For more information about AstraZeneca in the US or our AZ&Me(TM)
Prescription Savings programs, please visit:
http://www.astrazeneca-us.com or call +1-800-AZandMe (292-6363).
ONGLYZA is a trademark of the Bristol-Myers Squibb Company.
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