Chicago, IL, March 31, 2008 - New data from a clinical trial using intravascular ultrasound (IVUS) technology found that in patients living with type 2 diabetes, ACTOS® (pioglitazone HCl) reduced the atherosclerotic burden in the coronary arteries compared to glimepiride, and prevented progression compared to baseline. These data stem from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) trial.
The PERISCOPE trial was presented today as a late breaker at the 57th Annual Scientific Session of the American College of Cardiology in Chicago. This trial adds to the body of cardiovascular data for ACTOS. ACTOS studies, conducted over the past 10 years in more than 16,000 patients, including short- and long-term trials, as well as prospective and observational studies, have shown no evidence that ACTOS is associated with an increased risk of heart attack, stroke, or death.
"We are pleased with the results of the PERISCOPE, which further expands our cardiovascular data with ACTOS," said David P. Recker, M.D., senior vice president, Clinical Sciences and interim president at Takeda Global Research & Development. "While not definitive, data from PERISCOPE combined with results from a previous study, looking at surrogate endpoints, have shown a consistent trend toward decreasing cardiovascular risk by reducing the atherosclerotic burden in people with type 2 diabetes."
PERISCOPE is the first clinical trial to examine the effects of an oral antidiabetic medication on the development of coronary atherosclerosis in patients with type 2 diabetes using IVUS technology. The trial conducted in 97 centers in the U.S., Canada and Latin America with 543 patients, used IVUS imaging of the coronary arteries. The analysis demonstrated a statistically significant difference in percent change in coronary artery atheroma volume in favor of ACTOS treatment compared to glimepiride treatment.
The data showed that patients treated with glimepiride, a sulfonylurea and commonly used diabetes medication, exhibited progression of coronary atherosclerosis. In contrast, the ACTOS arm showed no progression of coronary atherosclerosis over the 18-month period from the initial baseline measurement.
Cardiovascular safety data was collected by looking at macrovascular events and episodes of congestive heart failure (CHF). The number of episodes of a common cardiovascular endpoint of cardiovascular mortality, non-fatal MI, or non-fatal stroke was 6 (2.2%) in glimepiride patients and 5 (1.9%) in ACTOS-treated patients. The number of hospitalizations due to CHF was equivalent in both arms. In the ACTOS-treated group, eight patients experienced a bone fracture, none involving the hip or spine.
Atherosclerosis is a condition that leads to reduced or blocked blood flow, and is accelerated in patients with type 2 diabetes. Atherosclerosis-related cardiovascular disease is the leading cause of death and disability in people with type 2 diabetes. Published data shows that slowed progression and reductions in atheroma volume lessens the incidence of a second heart attack. IVUS measures the volume of plaque build-up in the coronary arteries, a marker of coronary atherosclerosis.
The data are consistent with the findings of the CHICAGO (Carotid intima-media tHICkness in Atherosclerosis using pioGlitazOne) trial. Both PERISCOPE and CHICAGO support the findings of the PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events) trial, which showed that ACTOS was not associated with an increased risk of heart attack, stroke or death.
The CHICAGO Study
The CHICAGO trial was an 18-month, multicenter, randomized study that enrolled 462 patients with type 2 diabetes, all from the Chicago area. The primary goal was to compare the effects of ACTOS versus glimepiride, a sulfonylurea, on carotid intima-media thickness (CIMT), defined as the thickness of the inner lining of a patient's neck arteries. CIMT is an established surrogate marker of atherosclerosis. The CHICAGO analysis demonstrated a similar result on the progression of atherosclerosis as was observed in PERISCOPE.
The PROactive Study
The PROactive study was a prospective, randomized, placebo-controlled outcomes trial. The study included 5,238 patients with type 2 diabetes and a history of macrovascular disease, who were force-titrated up to 45 mg daily of either ACTOS or placebo in addition to standard of care. In this study, there was no difference in the number of macrovascular events between standard of care and ACTOS, and standard of care alone. Although there was no statistically significant difference between ACTOS and standard of care for the primary endpoint, there was no increase in mortality or total macrovascular events with ACTOS. In 2007, the ACTOS Prescribing Information was revised by the U.S. Food and Drug Administration to include this reassuring cardiovascular safety data.
ACTOS works by directly targeting insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels. ACTOS, a prescription medication, is taken once daily as an adjunct to diet and exercise, and is approved for use for type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas, or metformin.
Important Safety Information About ACTOS® (pioglitazone HCl)
ACTOS is not for everyone. Certain patients with heart failure should not start taking ACTOS. ACTOS can cause or worsen congestive heart failure. Talk to your doctor immediately if you experience rapid weight gain, fluid retention, or shortness of breath.
Do not take ACTOS if you have active liver disease. Your doctor should perform a blood test to check for liver problems before you start ACTOS and periodically thereafter. Talk to your doctor immediately if you experience nausea, vomiting, stomach pain, tiredness, loss of appetite, dark urine, or yellowing of the skin. If you are of childbearing age, talk to your doctor before taking ACTOS, as it could increase your chance of becoming pregnant. Some people taking ACTOS may experience flulike symptoms, mild-to-moderate swelling of legs and ankles, and anemia. Some people, particularly women, are at higher risk of having bone fractures while taking ACTOS. When taking ACTOS with insulin or sulfonylureas, you may be at risk for low blood sugar. Patients with diabetes should have regular eye exams. If you experience vision problems, consult your doctor immediately. Very rarely, some patients have experienced visual changes while taking ACTOS.
Please visit the ACTOS Web site at www.actos.com for Complete Prescribing Information.
Takeda Global Research & Development Center, Inc.
Based in Deerfield, Ill., and London, U.K., Takeda Global Research & Development Center, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. Takeda Global Research & Development was established in 2004 and is responsible for Takeda's clinical research and development in the U.S. and Europe, supporting clinical and product development activity for Takeda commercial organizations in the U.S. - Takeda Pharmaceuticals North America, Inc, and in Europe: six sales and marketing companies, respectively. With a robust pipeline of compounds in development for diabetes, cardiovascular disease and other conditions, Takeda rapidly brings innovative products to market to improve patient health and enhance the practice of medicine. To learn more about the company, visit www.tgrd.com.