Announcement Follows Recommendation of Data Safety Monitoring Committee and Executive Steering Committee
NEW YORK, May 27 /PRNewswire-FirstCall/ -- Pfizer Inc. (NYSE: PFE) announced that it plans to halt recruitment to the EMPHASIS-HF trial early on the recommendations of the trial's independent Executive Steering Committee (ESC). The recommendations follow a second interim analysis by the independent Data Safety Monitoring Committee (DSMC) of the EMPHASIS-HF trial confirming the study has reached its primary efficacy endpoint early according to the protocol pre-defined stopping rules.
The interim analysis showed that patients treated with INSPRA® (eplerenone), in addition to current standard of care, experienced a significant reduction in risk of cardiovascular (CV) death or heart failure (HF) hospitalization compared with those on the placebo arm of the trial where patients received standard of care in addition to a matching placebo.
Based upon the interim analyses by the independent data safety monitoring committee, eplerenone, generally, was well tolerated during the EMPHASIS-HF trial. Adverse events reported included hyperkalemia (elevated potassium) (8 per cent of the eplerenone group vs 3% in the placebo group; p < 0.001) and renal impairment (4 per cent in the eplerenone group vs 2% in the placebo group; p < 0.05). These adverse events are common with mineralcorticoid receptor antagonist agents.
The EMPHASIS-HF trial was a double-blind, placebo-controlled, parallel group trial comparing the effect of eplerenone plus standard heart failure therapy versus placebo plus standard heart failure therapy on mortality and morbidity outcomes in patients with mild chronic systolic heart failure (NYHA functional Class II) and left ventricular systolic dysfunction. The composite primary endpoints were the first occurrence of either cardiovascular (CV) death or heart failure (HF) hospitalization. The EMPHASIS-HF trial was to enroll approximately 3,100 patients and was to continue until a total of 813 adjudicated primary endpoint events were reported.
Inspra does not have a licence for use in the patient population studied in the EMPAHSIS-HF trial in any individual market.
Professor Faiez Zannad, Inserm and University of Nancy, France, co-Chair of the Executive Steering Committee, commented; "It is not common for clinical studies to conclude early for reasons of efficacy. The EMPHASIS-HF trial had an estimated end date around October 2011 so to have met the pre-defined efficacy endpoints early is certainly a positive outcome."
Pfizer has informed the relevant Regulatory Agencies, Ethics Committees/Independent Review Boards and Investigators as appropriate in countries where the trial was being conducted, and continues to work with the DSMC, Executive Steering Committee and all study investigators globally. In addition, Pfizer is working to ensure all patients are informed via their clinicians and an amendment to the protocol will be requested in order to allow all consenting patients to start treatment with eplerenone in an open label extension of the study, after completing a close-out visit ending the double-blind placebo-controlled phase.
About the EMPHASIS-HF trial
EMPHASIS HF (A6141079) is a phase IIIB, multinational (270 centers in approximately 30 countries), randomized, doubleblind placebocontrolled, parallelgroup trial. It is conducted in a NHYA II chronic systolic heart failure population, which is a distinct population from the EPHESUS study population (patients with left ventricular dysfunction (LVEF less than or equal to 40 %) and clinical evidence of heart failure after recent myocardial infarction).
The primary objective of this trial is to evaluate the efficacy and safety of eplerenone plus standard heart failure (HF) therapy versus placebo plus standard HF therapy on the cumulative incidence of cardiovascular (CV) mortality and HF hospitalization (a composite primary endpoint).
Patients were to be randomized (1:1) to receive eplerenone 25 mg once daily (OD) or matching placebo. At four weeks, the dose of study drug could be increased to 50 mg OD (two 25mg tablets of eplerenone or two matching placebo tablets once daily) based on serum potassium level. The trial was designed to enroll 3100 patients and to continue until a total of 813 adjudicated primary endpoint events were reported.
Inspra® (eplerenone) is a steroid nucleus-based mineralcorticoid receptor (MR) antagonist with a higher degree of selectivity than spironolactone. Eplerenone acts as a competitive and selective aldosterone blocker (SAB) at the mineralocorticoid receptor sites in various tissues throughout the body.
Inspra® Summary of Product Characteristics
UK prescribing information is available at: http://www.medicines.org.uk/EMC/medicine/16746/SPC/Inspra+25mg+%26+50+mg+film-coated+tablets/
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DISCLOSURE NOTICE: The information contained in this release is as of May 27, 2010. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about a potential additional indication for Inspra, including its potential benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; decisions by regulatory authorities regarding whether and when to approve any supplemental drug applications that may be filed for this additional indication for Inspra as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of any such additional indication; and competitive developments.
A further list and description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2009 and in its reports on Form 10-Q and Form 8-K.
SOURCE Pfizer Inc.