King Pharmaceuticals®, Inc. Reports DREAM Data On Ramipril; Results Presented At The European Association For The Study Of Diabetes And Published In The New England Journal of Medicine; Drug Fails In Diabetes Study
While the incidence of the development of type 2 diabetes in DREAM was lower overall among patients taking ramipril 15 mg compared to those taking placebo (18.1% among patients taking ramipril 15 mg compared to 19.5% in those taking placebo), the primary composite endpoint was not statistically different between ramipril and placebo by the end of the three-year follow-up period. Importantly, the rates of development of diabetes began to diverge between the ramipril and placebo treatment groups beginning in the third year, with lower rates in the ramipril-treated group, suggesting that a longer follow-up period may have enabled detection of a significant ramipril treatment effect with respect to the composite primary endpoint.
Although the median follow-up period was only 3 years, DREAM reinforced the beneficial metabolic effects of ramipril that were previously reported in the landmark Heart Outcomes Prevention Evaluation Trial ("HOPE"), which evaluated ramipril in a different patient population over a longer period of 4.5 years. DREAM showed a significant normalization of IFG and IGT in the ramipril-treated group compared to placebo (42.5% versus 38.2%; P=0.001). Additionally, two-hour post load glucose levels were significantly lower by study end in the ramipril-treated patients compared to placebo (P=0.01).
Also of significance, ramipril demonstrated a favorable effect on blood pressure compared to placebo. The mean baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) for the DREAM population was 136 mmHg and 83 mmHg, respectively. Ramipril 15 mg decreased SBP 8.2 mmHg and DBP 5.4 mmHg, compared to 3.9 mmHg and 3.0 mmHg, respectively, for placebo (P less than 0.001 for both SBP and DBP).
"Given that patients with elevated glucose levels or impaired glucose tolerance are at least at a 50% greater risk of cardiovascular disease, the apparent metabolic benefit demonstrated in the ramipril-treated patients in DREAM is of interest and worthy of additional investigation," said Jeffrey L. Probstfield, M.D., Professor of Medicine, Cardiology, at the University of Washington School of Medicine and the principal U.S. investigator for DREAM. "This finding suggests that a longer, or perhaps larger trial would be necessary to detect significant benefits of ramipril on the incidence of new onset diabetes and cardiovascular morbidity, if one exists, in this population of individuals."
Previously, HOPE demonstrated that ramipril produced a significant reduction in cardiovascular events such as stroke, myocardial infarction, and cardiovascular death across a broad spectrum of high risk patients with cardiovascular disease or diabetes. Analysis of the HOPE data also indicated that patients with cardiovascular disease treated with ramipril were 34% less likely to report a new diagnosis of diabetes compared to those randomized to placebo. DREAM was initiated to further investigate these positive metabolic results in non-diabetic patients without high cardiovascular risk.
"The data presented today demonstrate that the metabolic benefits of ramipril appear to extend beyond patients with high cardiovascular risk like those included in HOPE. DREAM excluded participants with uncontrolled hypertension, cardiovascular disease and heart failure," said Anne Peters, M.D., Professor of Clinical Medicine, Division of Endocrinology, University of Southern California Keck School of Medicine. "The benefit of normalizing glucose levels is important because IFG and IGT can be a precursor to diabetes."
In the study, ramipril 15 mg was well tolerated, with a safety profile consistent with current labeling for ramipril. The composite cardiorenal and renal data will be analyzed and reported separately.
DREAM was also designed to include a subset of subjects evaluated for the reduced risk of atherosclerosis with ramipril treatment. Results of the Study of Atherosclerosis with Ramipril and Rosiglitazone (STARR study) are expected to be presented later this year. The presentation of persistent DREAM results eight weeks after drug withdrawal is also expected.
"King Pharmaceuticals believes the results of DREAM are important to the medical community," said Charles L. Pamplin, III, M.D., Vice President of Medical Affairs for King Pharmaceuticals. "We look forward to further exploring the metabolic benefits of ramipril that were found in this study."
About DREAM
The DREAM Trial, conducted in 21 countries, screened nearly 25,000 people and ultimately enrolled a total of 5,269 non-diabetic subjects with IFG and/or IGT. According to the trial's 2x2 factorial design, subjects were randomized to receive ramipril 15 mg vs. placebo, rosiglitazone vs. placebo, or ramipril and rosiglitazone vs. placebo, and were followed for a median of three years. The primary endpoint of the trial was reduction in the development of diabetes or death from any cause during the study. Secondary endpoints included a reduction in cardiorenal events, improved beta cell function, and regression of dysglycemia to normal.
King Pharmaceuticals and Wyeth Pharmaceuticals contributed to the funding of the DREAM Trial.
About Ramipril
Ramipril, currently marketed by King Pharmaceuticals and Wyeth Pharmaceuticals as ALTACE(R) in the United States and Puerto Rico, has a rich clinical history as a front-line therapy for the treatment of hypertension and reduction in cardiovascular risk in a broad range of patients. It is the number one brand in the ACE Inhibitor class prescribed by cardiologists and endocrinologists.
ALTACE is indicated in patients 55 years or older at high risk of developing a major cardiovascular event, either because of a history of coronary artery disease, stroke, or peripheral vascular disease or because of diabetes that is accompanied by at least one other cardiovascular risk factor (hypertension, elevated total cholesterol levels, low HDL levels, cigarette smoking, or documented microalbuminuria), to reduce the risk of stroke, myocardial infarction, or death from cardiovascular causes. ALTACE can be used in addition to other needed treatments (such as antihypertensive, antiplatelet, or lipid-lowering therapies).
ALTACE is also indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.
Prescription ALTACE is not for everyone. ALTACE may cause swelling of the mouth, tongue, or throat, which could cause extremely serious risk and requires immediate medical care. There have been reports of low blood sugar in patients taking ALTACE with medicine for diabetes. Patients should contact their doctor if they have symptoms of low blood sugar such as sweating or shakiness. Common side effects include persistent dry cough, dizziness, and light-headedness due to low blood pressure.
ALTACE should not be taken during pregnancy, as death or injury to the unborn child may result, or if a person has experienced serious side effects related to previous ACE inhibitors. For more information about ALTACE and for a copy of important Product Information, please visit www.altace.com.
About King Pharmaceuticals
King, headquartered in Bristol, Tennessee, is a vertically integrated branded pharmaceutical company. King, an S&P 500 Index company, seeks to capitalize on opportunities in the pharmaceutical industry through the development, including through in-licensing arrangements and acquisitions, of novel branded prescription pharmaceutical products in attractive markets and the strategic acquisition of branded products that can benefit from focused promotion and marketing and product life-cycle management.
Contacts King Pharmaceuticals Inc., Bristol Investors: James E. Green, 423-989-8125 or David E. Robinson, 423-989-7045 or Sam Brown, Inc. Media: Mike Beyer, 773-463-4211 Beyer@sambrown.com