WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--MSD, known as Merck (NYSE: MRK) in the United States and Canada, today announced that the HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) study of TREDAPTIVE™ (modified-release nicotinic acid/laropiprant) did not meet its primary endpoint. MSD and the investigators are informing regulatory agencies of these results. The company is also preparing communications to health care providers in countries where the medicine is currently available, and will continue to work with regulators to provide updated information to health care providers. Based on the current understanding of these new data and until further analyses can be completed, MSD is recommending that providers not start new patients on TREDAPTIVE. MSD does not plan to seek regulatory approval for the medicine in the United States.
HPS2-THRIVE was independently conducted by the Clinical Trial Service Unit at Oxford University and funded by MSD. The study enrolled 25,673 patients considered to be at high risk for cardiovascular events. Of those enrolled, 14,741 were from Europe (the United Kingdom and Scandinavia) and 10,932 were from China. Patients in the study were followed for a median of 3.9 years. HPS2-THRIVE compared modified release nicotinic acid and laropiprant plus statin therapy versus statin therapy. It was not designed to assess directly the separate effects of either modified-release nicotini acid or laropiprant.
In the study, adding the combination of modified-release nicotinic acid and laropiprant to statin therapy did not significantly further reduce the risk of the combination of coronary deaths, non-fatal heart attacks, strokes or revascularizations compared to statin therapy. In addition, there was a statistically significant increase in the incidence of some types of non-fatal serious adverse events in the group that received modified-release nicotinic acid/laropiprant.
With the agreement of the independent research team at Oxford University, MSD is sharing results from the study with regulatory agencies in countries where the medicine is approved (under the brand names TREDAPTIVE or CORDAPTIVE) and in other countries as well. The investigators are conducting additional analyses, including regional analyses, to further understand the results. They anticipate reporting the detailed study results in the first quarter of 2013.
"While we are disappointed in these results, we thank the investigators who have conducted the study and the patients who have participated in it,” said Peter S. Kim, Ph.D., president, Merck Research Laboratories. “We are committed to working closely with the independent research team at Oxford University and with regulatory agencies to understand the results and determine next steps."
MSD encourages patients with any concerns to speak to their physician.
TREDAPTIVE/CORDAPTIVE has been approved in approximately 70 countries, including in Europe, and is sold in approximately 40 countries. TREDAPTIVE is also sold under the brand names PELZONT in Italy and TREVACLYN in Italy and Portugal. Sales through the first three quarters of 2012 were approximately $13 million.
Selected Product Information About TREDAPTIVE
TREDAPTIVE is indicated for the treatment of dyslipidemia, particularly in patients with combined mixed dyslipidemia (characterized by elevated levels of LDL-C and TG and low HDL-C) and in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial).
TREDAPTIVE should be used in patients in combination with HMG-CoA reductase inhibitors (statins), when the cholesterol-lowering effect of statin monotherapy is inadequate. It can be used as monotherapy only in patients in whom statins are considered inappropriate or not tolerated. Diet and other nonpharmacological treatments (e.g., exercise, weight reduction) should be continued during therapy with TREDAPTIVE.
Selected Safety Information About TREDAPTIVE
TREDAPTIVE is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients, significant or unexplained hepatic dysfunction, active peptic ulcer disease, or arterial bleeding.
The most common side effect of TREDAPTIVE is flushing (skin redness, warmth, and itching). Other common side effects include dizziness, headache, paresthesia, diarrhea, dyspepsia, nausea, vomiting, erythema, pruritus, rash, urticaria, feeling hot, and elevations in ALT or AST (consecutive, ≥ 3X ULN), fasting glucose, and uric acid.
Liver function tests are recommended before initiation, every 6 to 12 weeks for the first year, and periodically (e.g., semiannually) thereafter. Should an increase in ALT or AST of ≥3X ULN persist, reduction of dose or withdrawal of TREDAPTIVE is recommended
Physicians contemplating combined therapy with statins and TREDAPTIVE should carefully weigh the potential benefits and risks and should carefully monitor patients for myopathy (muscle pain, tenderness, or weakness), particularly during the initial months of therapy and when the dose of either drug is increased (periodic serum CK should be considered in such situations).
If muscle pain, weakness, or cramps occur while a patient is receiving TREDAPTIVE with a statin, their CK levels should be measured. If these levels are found, in the absence of strenuous exercise, to be significantly elevated (> 5X ULN), treatment should be stopped.
Caution should be used when treating Chinese patients with TREDAPTIVE coadministered with simvastatin or ezetimibe/simvastatin (particularly simvastatin doses of 40mg or higher) because of a higher than expected incidence of myopathy in those patients. Because the risk of myopathy with statins is dose-related, the use of TREDAPTIVE with simvastatin 80 mg or ezetimibe/simvastatin 10/80 mg is not recommended in Chinese patients. It is unknown whether there is an increased risk of myopathy in other Asian patients treated with TREDAPTIVE coadministered with simvastatin or ezetimibe/ simvastatin.
Diabetic or potentially diabetic patients should be observed closely. Adjustment of diet and/or hypoglycemic therapy may be necessary. TREDAPTIVE should be used with caution in patients with renal dysfunction, acute coronary syndrome, risk for hypophosphatemia, or gout (or predisposed to gout). As with other nicotinic acid products, TREDAPTIVE was associated with a small reduction in platelet count. Therefore, patients undergoing surgery should be carefully evaluated. Patients with a history of jaundice, hepatobiliary disorder, or peptic ulcer should be observed closely.
A clinical study to evaluate the effect of laropiprant on platelet function in patients concomitantly receiving both acetylsalicylic acid and clopidogrel was inconclusive. Because this study did not rule out the potential for prolongation of bleeding time, patients receiving TREDAPTIVE concomitantly with acetylsalicylic acid and clopidogrel should be closely monitored.
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