FDA Updates Label For AVANDIA(R) To Include Clinical Findings Demonstrating Sustained Glycemic Control For Up To Five Years

Main Category: Diabetes
Also Included In: Regulatory Affairs / Drug Approvals;  Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 15 Jul 2008 - 1:00 PST

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GlaxoSmithKline (NYSE: GSK) announces that the U.S. Food and Drug Administration (FDA) updated the prescribing information for AVANDIA(R) (rosiglitazone maleate) to include clinical findings from A Diabetes Outcome Progression Trial (ADOPT), a 4- to- 6 year head-to-head study of AVANDIA versus metformin and glyburide monotherapy in recently diagnosed type 2 diabetes patients. The percentage of patients with inadequate glucose control at five years was 34 percent with glyburide, 21 percent with metformin and only 15 percent with AVANDIA. The difference between AVANDIA and the comparators was statistically significant.

"GSK is pleased that the FDA has approved inclusion of the results from ADOPT, an important clinical trial that provides substantial long-term efficacy and safety data on AVANDIA compared to metformin and sulfonylurea," said Alexander R. Cobitz, MD, PhD, Senior Director, Metabolism, Clinical Development and Medical Affairs, GlaxoSmithKline. "As demonstrated in this study, patients treated with AVANDIA achieved greater sustained glycemic control. Better glycemic control has been proven to reduce risks of serious complications associated with type 2 diabetes including blindness, loss of limbs and kidney failure."

Study Design

ADOPT was a large, international, multi-center, randomized, double-blind, parallel-group study involving 4,351 people, aged 30-75 years who were recently diagnosed with type 2 diabetes (less than or equal to 3 years) from more than 400 sites throughout North America and Europe. ADOPT, conducted over a period of 4 to 6 years, assessed the cumulative incidence of monotherapy failure at five years with AVANDIA, metformin, glyburide, as defined by consecutive fasting plasma glucose (FPG) >180 mg/dL.

Patients were randomized to receive either AVANDIA 4 mg once daily, glyburide 2.5 mg once daily, or metformin 500 mg once daily, and doses were titrated to optimal glycemic control up to a maximum of 4 mg twice daily for AVANDIA, 7.5 mg twice daily for glyburide, and 1,000 mg twice daily for metformin. Initial treatment with AVANDIA reduced the risk of monotherapy failure in people with type 2 diabetes by 32 percent compared to metformin (p<0.001), and 63 percent compared to glyburide (p<0.001) at five years.

Safety Information from ADOPT

In ADOPT, AVANDIA was reported to be generally well-tolerated among the large cohort of people with type 2 diabetes who were followed for up to six years. Incidence of congestive heart failure (CHF) adverse events was the same among patients treated with AVANDIA (0.8 percent) and metformin (0.8 percent); however, people given glyburide experienced a lower rate of CHF events (0.2 percent).

Over the duration of the study, commonly reported adverse events included edema, weight gain and hypoglycemia.

In ADOPT, significantly more women treated with AVANDIA experienced fractures than did those who received either metformin or glyburide. The majority of fractures observed were in the upper arm, hand, or foot. However, the number of women with a hip or spine fracture was low and similar among the three treatment groups. The incidence of fractures for men in ADOPT was similar among the three treatment groups.

Other cardiovascular safety data for AVANDIA in ADOPT were added to the label in November 2007 and show that the results for three endpoints (major cardiovascular events, heart attacks and total mortality) were not statistically significantly different between AVANDIA and comparators.

About GlaxoSmithKline

GlaxoSmithKline -- one of the world's leading research-based pharmaceutical and healthcare companies -- is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, visit GlaxoSmithKline on the World Wide Web at http://www.gsk.com.

Important Safety Information for AVANDIA(R) (rosiglitazone maleate)

AVANDIA, along with diet and exercise, helps improve blood sugar control in patients with type 2 diabetes.

AVANDIA can cause or worsen heart failure. If you have severe heart failure (very poor pumping ability of the heart), you cannot be started on AVANDIA. AVANDIA is also not recommended if you have heart failure with symptoms (such as shortness of breath or swelling) even if these symptoms are not severe.

AVANDIA may increase your risk of other heart problems that occur when there is reduced blood flow to the heart, such as chest pain (angina) or heart attack (myocardial infarction). This risk appeared higher in patients taking medicines called nitrates or insulin. Taking AVANDIA with insulin or with nitrates is not recommended.

If you have chest pain or a feeling of chest pressure, you should seek immediate medical attention, regardless of what diabetes medicines you are taking.

If you take AVANDIA, tell your doctor right away if you:

-- Have swollen legs or ankles, a rapid increase in weight or difficulty breathing, or unusual tiredness

-- Experience changes in vision

-- Become pregnant

-- Review your medical history and tell your doctor if you:

-- Have heart failure or other heart problems

-- Have liver problems or liver disease

-- Are pregnant or are nursing

Women taking AVANDIA should know that AVANDIA may increase the risk of pregnancy. More fractures have been observed in women taking AVANDIA.

For more information about AVANDIA, please see Patient Information. For further information on Avandia, please see full Prescribing Information.

GlaxoSmithKline
http://www.gsk.com