ALISO VIEJO, Calif.,
June 30, 2015 /PRNewswire/
-- Avanir Pharmaceuticals, Inc. today announced
top-line data from the PRISM II study showing that treatment with
NUEDEXTA® was associated with a statistically
significant reduction in symptoms of pseudobulbar affect (PBA) in
patients with traumatic brain injury (TBI) or stroke. PBA is a
distressing condition characterized by sudden and uncontrollable
outbursts of laughing and/or crying resulting from certain
neurologic diseases or brain injury. PRISM II is a phase IV study
evaluating the safety and effectiveness of NUEDEXTA in treating PBA
in patients with dementia/Alzheimer's disease, stroke and TBI. Data
from patients with PBA secondary to TBI were presented Monday, June 29th at the 33rd Annual
Symposium of the National Neurotrauma Society in Santa Fe, New Mexico. Data from patients with
PBA secondary to dementia/Alzheimer's disease were presented at
last year's American Neurological Association Meeting, and full
results from the stroke cohort will be presented at a future
date.
"The improvement in PBA symptoms that we saw in the TBI and
stroke cohorts of this study are consistent with what we saw in the
pivotal phase III study of PBA in patients with multiple sclerosis
(MS) and amyotrophic lateral sclerosis (ALS), as well as that seen
for PBA patients with dementia also enrolled in PRISM II. The data
show that physicians, patients and caregivers see treatment
benefit, providing further evidence that NUEDEXTA can offer relief
from the disruptive and debilitating effects of PBA," said
Joao Siffert, M.D., executive vice
president, R&D, and chief medical officer at Avanir. "We have
now studied NUEDEXTA in over 1,000 patients of different ages,
including many above 70 years of age, who had PBA resulting from a
wide variety of neurological disorders. In all groups, we have seen
consistent levels of effectiveness and safety."
Enrollment in PRISM II is complete with 134 patients with PBA in
the dementia/Alzheimer's disease cohort, 120 patients with PBA in
the TBI cohort, and 113 patients with PBA in the stroke cohort. The
average age of patients in this study was 72 for
dementia/Alzheimer's disease, 61 for stroke and 46 for TBI. The
effectiveness endpoints included a PBA symptom rating scale called
the Center for Neurologic Study-Lability Scale (CNS-LS; scored from
7 = no symptoms to 35 = maximum symptoms), the number of weekly PBA
episodes, the degree to which PBA symptoms affected overall quality
of life (QOL; 0 = "Not at all" and 10 = "Significantly"), and
Clinician and Patient Global Impression of Change with respect to
PBA (CGI-C; PGI-C). Standard safety measures were recorded
throughout the study.
TBI Cohort Top-Line Results
- At baseline, patients had a mean CNS-LS score of 20.5 and were
suffering from a median of 10 PBA episodes per week.
- At the end of the study period, mean CNS-LS improved to 11.9
(P<0.001 compared with baseline) and the median number of
PBA episodes decreased to one per week, with an overall 78.5%
reduction in episode count compared to baseline
(P<0.001).
- Consistent improvement was observed in other effectiveness
endpoints.
- 73.0% of patients or caregivers rated themselves/the patient as
being much/very improved on the PGI-C (P<0.001).
- 78.0% of clinicians rated the patient to be much/very much
improved on the CGI-C (P<0.001).
- Adverse events (AE) were reported by 43 patients (35.8%) with
23 (19.2%) having an AE deemed to be treatment-related. The most
commonly reported AE was diarrhea (8.3%). A total of four patients
had serious AEs (none of which were deemed to be
treatment-related), and 14 patients discontinued the study due to
AEs. The AE profile was generally consistent with that observed in
other trials of NUEDEXTA.
Stroke Cohort Top-Line Results
- At baseline, patients had a mean CNS-LS score of 20.8 and were
suffering from a median of 10 PBA episodes per week.
- At the end of the study period, mean CNS-LS improved to 13.1
(P<0.001 compared with baseline) and the median number of
PBA episodes decreased to two per week with an overall 75.5%
reduction in episode count compared to baseline
(P<0.001).
- Consistent improvement was observed in other effectiveness
endpoints.
- 68.0% of patients or caregivers rated themselves/the patient as
being much/very improved on the PGI-C (P<0.001).
- 75.0% of clinicians rated the patient to be much/very much
improved on the CGI-C (P<0.001).
- AEs were reported by 40 patients (35.4%) with 16 (14.2%) having
an AE deemed to be treatment-related. The most commonly reported
AEs were diarrhea (4.4%), headache (3.5%) and constipation (2.7%).
A total of seven patients had serious AEs (none of which were
deemed to be treatment-related), and six patients discontinued the
study due to AEs. This AE profile was generally consistent with
that observed in other trials of NUEDEXTA.
About PRISM II
The objectives of the study were to
evaluate 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 ALS and 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.
The CNS-LS has been validated in ALS and MS patients.
Poster Presentation Details:
Title: Safety,
Tolerability, and Effectiveness of Dextromethorphan/Quinidine for
Pseudobulbar Affect in Traumatic Brain Injury: PRISM II
Poster Number: A2-01
Poster Session: A2 Poster Session I – Group A: Secondary Injury
Presentation Time: Monday, June 29th
at 7:00 a.m. MDT
About PBA
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. As a result, many of those afflicted with PBA show
significant impairment on standard measures of health status, and
impairments in occupational and social function, often leading to
social isolation. 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.
About NUEDEXTA
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.
©2015 Avanir Pharmaceuticals, Inc. All Rights Reserved.
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