52-Week Study Finds ONGLYZA(TM) (saxagliptin) When Added To Metformin Was Non-Inferior To Titrated Glipizide When Added To Metformin In Reducing Glycosylated Hemoglobin (HbA1c) In Adults With Type 2 Diabetes MellitusBy Bristol-myers Squibb And Astrazeneca, PRNE
Friday, June 25, 2010
Not for US Media
ORLANDO, Florida, June 26, 2010 - Bristol-Myers Squibb Company (NYSE: BMY)
and AstraZeneca (NYSE: AZN) 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 Scientific Sessions.
"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, Germany.
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 insulin.
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 52.
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 mellitus.
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
- 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.
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
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 telithromycin).
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 www.bms.com.
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 at
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:
www.astrazeneca-us.com or call +1-800-AZandMe (292-6363).
ONGLYZA is a trademark of the Bristol-Myers Squibb Company.
Contacts: Media: Ken Dominski, Bristol-Myers Squibb, +1-609-252-5251,
ken.dominski at bms.com; Corey Windett, AstraZeneca, +1-302-885-0034,
corey.windett at astrazeneca.com; Investors: John Elicker, Bristol-Myers Squibb, +1-609-252-4611,
john.elicker at bms.com; Karl Hard, AstraZeneca, +44-20-7304-5322, karl.j.hard at astrazeneca.com; Clive Morris, AstraZeneca, +44-20-7304-5084, clive.morris at astrazeneca.com
Tags: Bristol-myers Squibb And Astrazeneca, florida, June 26, Orlando, United States of America
June 27, 2010: 2:55 am
saxa,sita ,and vildagliptin which one is superior and why?