Avanir Pharmaceuticals Announces Enrollment of First Patient in PRIME Study of AVP-923 in Central Neuropathic Pain in Multiple Sclerosis
"With approximately 400,000 people in the U.S suffering from MS, there is clearly a need for effective and safe therapies to treat symptoms associated with this disease such as central neuropathic pain," said Andrew Goodman, MD, professor of neurology at the University of Rochester. "Neuropathic pain remains inadequately treated in many people with MS and significantly interferes with daily functioning of those affected."
About the PRIME Study
The objectives of the PRIME (Pain Research In Multiple sclErosis) study are to evaluate the safety, tolerability, and efficacy of AVP-923 for the treatment of central neuropathic pain in patients with multiple sclerosis. The trial is a multicenter, randomized, double-blind, placebo-controlled, 4-arm parallel group study. Eligible patients will receive one of three dose levels of AVP-923 containing either 45mg DM/10 mg Q, 30mg DM/10mg Q, 20mg DM/10mg Q or placebo, daily for 12 weeks. The primary efficacy endpoint will be measured based on the Numeric Pain Rating Scale as recorded in patient diaries. Secondary assessments include measures of fatigue, impact of MS on daily life, sleep quality, cognition and depression. Safety will be assessed by monitoring adverse events, clinical laboratory tests, ECGs and physical examinations.
Avanir expects to enroll approximately 400 patients both in the U.S. and internationally.
"The initiation of this clinical study is an important step in the continued development of AVP-923," said Joao Siffert, MD, senior vice president of research and development at Avanir. "With no approved therapies for central neuropathic pain in MS, we are very excited about the potential application of AVP-923 as a safe and effective treatment option. In addition, we look forward to exploring the potential of AVP-923 across a broad range of other CNS disorders."
About Multiple Sclerosis and Central Neuropathic Pain
Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system (CNS) that causes abnormal function of the motor, sensory and visual systems. The initial disease course is often characterized by multiple exacerbations and remissions, with symptoms determined by the location and extent of the demyelinating areas in the brain and spinal cord. Chronic pain affects nearly half of all MS patients and has a substantial impact on daily life, further affecting their ability to function and work. MS patients experience pain of several types including musculoskeletal pain, painful tonic spasms and neuropathic pain, including trigeminal neuralgia, Lhermitte's sign and central neuropathic pain affecting the limbs. Central neuropathic pain is caused by lesions of sensory pathways in the brain and spinal cord and is estimated to affect approximately 30% of MS patients. It is characterized by moderate to severe painful sensations of burning, pricking, electric shocks and squeezing overlying areas of numbness. Common analgesics provide inadequate relief and there are no FDA-approved drugs for the treatment of central neuropathic pain.
AVP-923 is a combination of two well-characterized compounds: the active ingredient dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist) and low dose quinidine sulfate (a CYP2D6 enzyme inhibitor), which serves to increase the bioavailability of dextromethorphan. The dosage form of AVP-923 of 20 mg DM/10 mg Q capsules (twice daily) is approved by the FDA under the brand name NUEDEXTA® which is indicated for the treatment of pseudobulbar affect (PBA).
NUEDEXTA® is the first and only FDA-approved treatment for pseudobulbar affect (PBA). NUEDEXTA is an innovative combination of two well-characterized components; dextromethorphan hydrobromide (20 mg), the ingredient active in the central nervous system, and quinidine sulfate (10 mg), a metabolic inhibitor enabling therapeutic dextromethorphan concentrations. NUEDEXTA acts on sigma-1 and NMDA receptors in the brain, although the mechanism by which NUEDEXTA exerts therapeutic effects in patients with PBA is unknown.
NUEDEXTA is not approved for the treatment of central neuropathic pain.
NUEDEXTA Important Safety Information
NUEDEXTA can interact with other medications causing significant changes in blood levels of those medications and/or NUEDEXTA. NUEDEXTA is contraindicated in patients receiving drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine and pimozide) and should not be used concomitantly with other drugs containing quinidine, quinine, or mefloquine. NUEDEXTA is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days. NUEDEXTA is contraindicated in patients with a known hypersensitivity to its components.
NUEDEXTA may cause serious side effects, including possible changes in heart rhythm. NUEDEXTA is contraindicated in patients with a prolonged QT interval, congenital long QT syndrome or a history suggestive of torsades de pointes, in patients with heart failure as well as patients with, or at risk of, complete atrioventricular (AV) block, unless the patient has an implanted pacemaker.
NUEDEXTA causes dose-dependent QTc prolongation. When initiating NUEDEXTA in patients at risk of QT prolongation and torsades de pointes, electrocardiographic (ECG) evaluation of QT interval should be conducted at baseline and 3-4 hours after the first dose.
The most common adverse reactions in patients taking NUEDEXTA are diarrhea, dizziness, cough, vomiting, weakness, swelling of feet and ankles, urinary tract infection, flu, elevated liver enzymes, and flatulence.
NUEDEXTA may cause dizziness. Precautions to reduce the risk of falls should be taken, particularly for patients with motor impairment affecting gait or a history of falls.
Patients should take NUEDEXTA exactly as prescribed. Patients should not take more than 2 capsules in a 24-hour period, make sure that there is an approximate 12-hour interval between doses, and not take a double dose after they miss a dose.
These are not all the risks from use of NUEDEXTA. For additional important safety information about NUEDEXTA, please see the full Prescribing Information at www.NUEDEXTA.com.
About Avanir Pharmaceuticals, Inc.
Avanir Pharmaceuticals, Inc. is a biopharmaceutical company focused on bringing innovative medicines to patients with central nervous system disorders of high unmet medical need. Avanir is dedicated to advancing medicines that can substantially improve the lives of patients and their loved ones. For more information about Avanir, please visit www.avanir.com.
Avanir™ and NUEDEXTA® are trademarks owned by Avanir Pharmaceuticals, Inc.
©2011 Avanir Pharmaceuticals, Inc. All Rights Reserved.
Forward Looking Statements
Except for the historical information contained herein, the matters set forth in this press release, including statements regarding Avanir's plans, potential opportunities, financial or other expectations, projections, goals objectives, milestones, strategies, market growth, timelines, legal matters, product pipeline, clinical studies, product development and the potential benefits of its commercialized products and products under development are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the risks and uncertainties associated with meeting the objectives of the PRIME study, including, but not limited to, delays or failures in enrollment, and the occurrence of adverse safety events, and other risks detailed from time to time in the Company's most recent Annual Report on Form 10-K and other documents subsequently filed with or furnished to the Securities and Exchange Commission. These forward-looking statements are based on current information that may change and you are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and the Company undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance of this press release.
Avanir Investor & Media Contact
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