ALISO VIEJO, Calif., July 23, 2015 /PRNewswire/ -- Avanir Pharmaceuticals, Inc. today announced new findings from the dementia/Alzheimer's disease cohort of the PRISM II study, a phase IV study evaluating the safety and effectiveness of NUEDEXTA® in treating pseudobulbar affect (PBA) in patients with dementia/Alzheimer's disease, stroke and traumatic brain injury (TBI). PBA is a distressing condition characterized by sudden and uncontrollable outbursts of laughing and/or crying resulting from certain neurologic diseases or brain injury. The data were presented at the 2015 Alzheimer's Association International Conference (AAIC) in Washington, D.C., along with two additional presentations related to Avanir's program in agitation secondary to Alzheimer's disease.
"PBA is often treated with antidepressants, so we wanted to analyze the differential effects of NUEDEXTA based on concomitant antidepressant usage in patients with PBA secondary to dementia/Alzheimer's disease who enrolled in the PRISM II study," said Joao Siffert, M.D., executive vice president, R&D, and chief medical officer at Avanir. "In the study, the treatment benefit with NUEDEXTA on PBA symptoms was the same whether or not the patient was on antidepressants when they enrolled in the study."
New Data Demonstrate Treatment Effects on PBA with Dextromethorphan/Quinidine Regardless of Concomitant Antidepressant Use in Dementia/Alzheimer's Disease Cohort of PRISM II Study
New post-hoc analysis analyzed the differential effects on PBA of NUEDEXTA based on concomitant antidepressant usage in patients with PBA secondary to dementia/Alzheimer's disease. At baseline, 76 patients (57.0%) were receiving concomitant antidepressants. Improvements in mean Center for Neurologic Study-Lability Scale (CNS-LS) score at final visit vs. baseline and PBA episode count were significant (P<0.001 for all) irrespective of antidepressant use. Similar percentages of antidepressant users vs. non-users were rated "much"/"very much" improved on Patient Global Impression of Change (PGI-C;74.1% vs. 79.5%) and Clinician Global Impression of Change (CGI-C;74.1% vs. 81.8%). Adverse events (AEs) occurred in 28 (36.8%) concomitant antidepressant users vs. 21 (36.2%) non-users. The most common AEs were headache (7.9% vs. 6.9%), urinary tract infection (2.6% vs. 6.9%), and diarrhea (2.6% vs 5.2%).
Title: Dextromethorphan/Quinidine for Treatment of Pseudobulbar Affect in Patients with Dementia: Treatment Effects by Concomitant Antidepressant Use in a 12-week Open-Label Trial (PRISM II)
Presentation Number: 04-09-06
Time: Wednesday, July 22, 4:15 p.m. ET
New Data Demonstrate Minimal Difference Between Patient-Reported and Caregiver Reported Outcomes in Dementia/Alzheimer's Disease Cohort of PRISM II Study
New post-hoc analysis from the dementia/Alzheimer's disease cohort of the PRISM II study compared patient-completed and caregiver-completed ratings for all effectiveness measures that were consistently completed by the same reporter at all time-points. Caregiver-proxy vs. patient-completed ratings did not differ significantly across these measures, except for PBA episode counts. The difference in the patient and caregiver reports for this measure could potentially be related to the patient's memory deficits, lack of awareness, or both.
Poster Presentation Details:
Title: Dextromethorphan/Quinidine for Treatment of Pseudobulbar Affect in Patients With Dementia: Comparison of Patient-Reported Ratings to Those of Caregiver Proxies in a 12-Week Open-Label Trial (PRISM II)
Poster Number: P1-300
Time: Sunday, July 19, 9:30 a.m. – 4:15p.m. ET
Dextromethorphan/Quinidine Significantly Improved PBA Symptoms of Both Uncontrollable Laughing and Crying in Dementia/Alzheimer's Disease Cohort of PRISM II Study
Additional analysis of the CNS-LS and individual CNS-LS Item Scores showed that NUEDEXTA significantly improved PBA symptoms of both uncontrollable laughing and uncontrollable crying. In addition, despite open-label limitations of the study, reduction in CNS-LS was similar to that in the NUEDEXTA phase III pivotal trial in patients with PBA secondary to ALS or MS.
Poster Presentation Details:
Title: Dextromethorphan/Quinidine for Treatment of Pseudobulbar Affect in Patients With Dementia: Examination of CNS-LS Outcomes in a 12-Week Open-Label Trial (PRISM II)
Poster Number: P3-290
Time: Tuesday, July 21, 9:30 a.m. – 4:15 p.m. ET
About PRISM II
PRISM II is a phase IV study that evaluated the safety, tolerability and effectiveness of NUEDEXTA capsules containing 20 mg dextromethorphan hydrobromide (DM) and 10 mg quinidine sulfate (Q) for treatment of PBA in patients with Alzheimer's disease and other dementias, stroke and traumatic brain injury.
PRISM II is a nationwide, open-label, multicenter study that enrolled 367 patients at approximately 100 study centers. Eligible patients were age ≥18 years with a clinical diagnosis of PBA and baseline score ≥13 on the CNS-LS. Patients with TBI due to a penetrating head injury were excluded. Patients were treated with NUEDEXTA twice daily for 12 weeks. The primary endpoint was change from baseline in PBA symptoms as measured by the CNS-LS, an instrument originally validated as a measure of PBA episode frequency and severity in patients with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Determination of effectiveness was based on a comparison of CNS-LS change in PRISM II with that seen for NUEDEXTA and placebo in a previous pivotal phase III study. Additional outcomes measures included number of weekly PBA episodes (laughing and/or crying); Mini-Mental State Examination; PBA impact on quality of life; CGIC; PGIC; patients' satisfaction with treatment; Patient Health Questionnaire (PHQ-9; to evaluate mood symptoms), and a functional measure consisting of the Neurobehavioral Functioning Inventory for patients with TBI and Stroke Impact Scale for patients with stroke. Safety measures included monitoring of adverse events, concomitant medication usage, and vital signs.
PBA is a neurologic condition characterized by uncontrollable, disruptive laughing and/or crying outbursts that are often contrary or exaggerated to the patient's inner mood state. PBA occurs secondary to a variety of neurologic conditions such as traumatic brain injury (TBI), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Parkinson's disease, stroke and Alzheimer's disease. When these disorders damage areas of the brain that regulate normal emotional expression, they can lead to uncontrollable, disruptive episodes of crying or laughing. For more information about PBA, please visit www.PBAFacts.com.
NUEDEXTA is an innovative combination of two well-characterized components, dextromethorphan hydrobromide, the ingredient active in the central nervous system, and quinidine sulfate, a metabolic inhibitor enabling therapeutic dextromethorphan concentrations. Dextromethorphan 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 Important Safety Information
NUEDEXTA is indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of otherwise unrelated neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or incongruent to the underlying emotional state. PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurological disease or injury.
NUEDEXTA (dextromethorphan hydrobromide and quinidine sulfate) 20mg/10mg capsules can interact with other medications causing significant changes in blood levels of those medications and/or NUEDEXTA which may lead to serious side effects. Adjust dose or use alternate treatment of the other medication when clinically indicated.
NUEDEXTA is contraindicated in patients concomitantly taking: QT-prolonging drugs metabolized by CYP2D6 (e.g., thioridazine and pimozide); monoamine oxidase inhibitors (MAOIs) within the preceding or following 14 days; other drugs containing quinidine, quinine, or mefloquine and in patients with a known hypersensitivity to these drugs or any of NUEDEXTA's components.
Discontinue use of NUEDEXTA if hepatitis, thrombocytopenia, serotonin syndrome or a hypersensitivity reaction occurs.
NUEDEXTA is contraindicated in patients with certain risk factors for arrhythmia: Prolonged QT interval; congenital long QT syndrome, history suggestive of torsades de pointes; heart failure; complete atrioventricular (AV) block or risk of AV block without an implanted pacemaker.
NUEDEXTA causes dose-dependent QTc prolongation. When initiating NUEDEXTA in patients at risk for QT prolongation and torsades de pointes, electrocardiographic (ECG) evaluation should be conducted at baseline and 3-4 hours after the first dose. Risk factors include left ventricular hypertrophy or dystrophy or concomitant use of drugs that prolong QT interval or certain CYP3A4 inhibitors.
The most common adverse reactions are diarrhea, dizziness, cough, vomiting, asthenia, peripheral edema, urinary tract infection, influenza, increased gamma-glutamyltransferase, 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.
These are not all the risks from use of NUEDEXTA®. Please refer to the accompanying full Prescribing Information or visit 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. As part of our commitment, we have extensively invested in our pipeline and are dedicated to advancing medicines that can substantially improve the lives of patients and their loved ones. For more information about Avanir, please visit http://www.avanir.com.
Avanir is a subsidiary of Otsuka America, Inc. (OAI), a holding company established in the U.S. in 1989. OAI is wholly owned by Otsuka Pharmaceutical Co., Ltd., a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.'
Otsuka Pharmaceutical is a leading firm in the challenging area of mental health and also has products and research programs for several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate more powerfully than words how Otsuka is a "big venture" company at heart, applying a youthful spirit of creativity in everything it does.
Otsuka Pharmaceutical and its affiliates employ approximately 30,000 people globally, and the company welcomes you to visit its global website at: http://www.otsuka.co.jp/en/index.php
Avanir® is a trademark or registered trademark of Avanir Pharmaceuticals, Inc. in the United States and other countries.
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