Teva Neuroscience, Inc.: Clinical Pharmacology Study With AZILECT(R) (Rasagiline Tablets) Demonstrated It Does Not Increase Tyramine Sensitivity
Published: Jun 09, 2009
Study Indicated Rasagiline Selectivity for Inhibiting MAO-B at Maximum Approved Dose
KANSAS CITY, Mo., June 9 /PRNewswire/ -- Teva Neuroscience, Inc. today presented results from a clinical pharmacology study in which AZILECT(R) (rasagiline tablets) did not increase the risk of tyramine sensitivity at the maximum approved dose of 1 mg. The presentation was made during the 13th International Congress of Parkinson's Disease and Movement Disorders in Paris, France. This study assessed the potential risk of hypertensive crisis due to the interaction between high doses of oral tyramine and therapeutic doses of rasagiline, which is indicated both as monotherapy in patients with early Parkinson's disease (PD) and as adjunctive treatment in patients receiving levodopa. The study supported the selectivity of rasagiline for inhibition of MAO-B at currently approved doses.
"We are pleased with the results, which met our primary objectives," said Jon Congleton, general manager of Teva Neuroscience. "This study provides continuing evidence of the value of AZILECT. The results demonstrated a low potential for MAO-A and therefore a selectivity for MAO-B inhibition."
The clinical pharmacology trial was a double-blind, placebo-controlled, randomized, dose-ranging study of rasagiline using a positive control (phenelzine) and a comparator drug (selegiline). The study results were based on the Tyramine Sensitivity Factor (TSF), which measures the ratio of tyramine pressor dose before (baseline) and after MAO inhibitor administration. Geometric mean TSFs of all doses of rasagiline were substantially lower than the TSF for phenelzine, a known nonselective MAO inhibitor. TSFs of various doses of rasagiline were comparable to those of selegiline and placebo.
Tyramine is an amino acid found in certain foods and beverages, including some air-dried and fermented meats, some aged cheeses and most soybean products. Nonselective MAO inhibitors, such as phenelzine sulfate, interfere with the breakdown and elimination of tyramine in the body. Selective MAO-B inhibitors do not interfere with tyramine breakdown and elimination. Patients who take nonselective MAO inhibitors need to be cautious with the foods they eat to prevent an abnormal build-up of tyramine, which could lead to an episode of extremely high blood pressure, potentially leading to stroke or heart attack.
This study was performed as part of a Phase IV commitment to the U.S. Food and Drug Administration (FDA) at the time of AZILECT approval. The results of this study have been submitted to FDA, and Teva Neuroscience intends to work with FDA to appropriately incorporate these results into the label for AZILECT.
About the Study
The tyramine trial was a double-blind, placebo-controlled, randomized, dose-ranging study of rasagiline using a positive control (phenelzine) and a comparator drug (selegiline). In the study, 179 healthy male and female volunteers, aged 40 to 70 years, entered a run-in tyramine challenge test with escalating doses of oral tyramine from 25 mg up to 800 mg administered under fasting conditions. TSF was calculated as the tyramine dose associated with 3 consecutive increases from baseline in SBP >/=30 mm Hg over >/=10 minutes (tyramine pressor dose) in period 1 divided by the dose associated with the same change in SBP in period 3. Nonselective comparator, phenelzine, caused the highest geometric mean TSF of 17.32 +/- 12.76. Geometric mean TSF for rasagiline 1 mg once daily, the maximum approved dose, was 2.03 compared with 1.50 for pooled placebo and 2.47 for selegiline.
AZILECT(R) (rasagiline tablets) is indicated for the treatment of the signs and symptoms of Parkinson's disease (PD) both as initial therapy alone and to be added to levodopa later in the disease.
IMPORTANT SAFETY INFORMATION ABOUT AZILECT
Patients should not take AZILECT if they are taking meperidine as it could result in a serious reaction such as coma or death. Also, patients should not take AZILECT with tramadol, methadone, propoxyphene, dextromethorphan, St. John's wort, mirtazapine, or cyclobenzaprine.
Patients should not take AZILECT with other monoamine oxidase inhibitors (MAOIs), amphetamines, cold remedies containing decongestants and weight-reducing preparations containing pseudoephedrine, phenylephrine, phenylpropanolamine, or ephedrine in order to avoid a possibly dangerous increase in blood pressure.
Patients with moderate to severe liver disease or a tumor of the adrenal gland should not take AZILECT.
In order to prevent a possibly dangerous increase in blood pressure, patients taking AZILECT should avoid foods and beverages high in tyramine content such as aged cheeses, air-dried meats, pickled herring, tap/draft beers, sauerkraut, and soy sauce.
Patients should inform their physician if planning any surgical procedures. Patients should inform their physician if they are taking, or planning to take, any prescription or over-the-counter drugs, especially antidepressants and ciprofloxacin. All PD patients should be monitored for melanoma (skin cancer) on a regular basis.
Side effects seen with AZILECT alone are headache, joint pain, and indigestion; and when taken with levodopa are uncontrolled movements (dyskinesias), accidental injury, nausea, weight loss, constipation, low blood pressure when standing, joint pain, vomiting, dry mouth, rash, and sleepiness.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
About Parkinson's Disease
Parkinson's disease is an age-related degenerative disorder of the brain. Symptoms can include: tremor, stiffness, slowness of movement, and impaired balance. An estimated five million people worldwide suffer from the disease, with an average age of onset of about 60 years.
Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the world's leading generic pharmaceutical company. The Company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients, as well as animal health pharmaceutical products. Over 80 percent of Teva's sales are in North America and Europe.
Teva's U.S. innovative product marketing subsidiary, Teva Neuroscience, Inc., promotes AZILECT(R) (rasagiline tablets) in the United States. AZILECT is a registered trademark of Teva Pharmaceutical Industries Ltd. Please visit www.AZILECT.com for additional important information, or see the enclosed additional important information.
Safe Harbor Statement under the U. S. Private Securities Litigation Reform Act of 1995:
This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on management's current beliefs and expectations and involve a number of known and unknown risks and uncertainties that could cause our future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the extent to which we may obtain U.S. market exclusivity for certain of our new generic products and regulatory changes that may prevent us from utilizing exclusivity periods, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, including that relating to the generic versions of Neurontin(R), Lotrel(R) and Protonix(R), the current economic conditions, competition from brand-name companies that are under increased pressure to counter generic products, or competitors that seek to delay the introduction of generic products, the effects of competition on our innovative products, especially Copaxone(R) sales, dependence on the effectiveness of our patents and other protections for innovative products, especially Copaxone(R), the impact of consolidation of our distributors and customers, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry, our ability to achieve expected results though our innovative R&D efforts, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Agency and other regulatory authority approvals, the uncertainty surrounding the legislative and regulatory pathway for the registration and approval of biotechnology-based products, the regulatory environment and changes in the health policies and structures of various countries, supply interruptions or delays that could result from the complex manufacturing of our products and our global supply chain, our ability to successfully identify, consummate and integrate acquisitions, including the integration of Barr Pharmaceuticals, Inc., the potential exposure to product liability claims to the extent not covered by insurance, our exposure to fluctuations in currency, exchange and interest rates, significant operations worldwide that may be adversely affected by terrorism, political or economical instability or major hostilities, our ability to enter into patent litigation settlements and the intensified scrutiny by the U.S. government, the termination or expiration of governmental programs and tax benefits, impairment of intangible assets and goodwill, environmental risks, and other factors that are discussed in our Annual Report on Form 20-F and in our other filings with the U.S. Securities and Exchange Commission ("SEC").
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Web site: http://www.azilect.com/