



ACURA PHARMACEUTICALS
AND KING PHARMACEUTICALS
ANNOUNCE
POSITIVE TOP LINE RESULTS OF KEY CLINICAL STUDY
ASSESSING ABUSE LIABILITY
Acurox™ Tablets
Significantly Disliked
When Excess Doses
Are Swallowed
PALATINE, ILLINOIS and BRISTOL,
TENNESSEE -
October 13, 2008
–
Acura Pharmaceuticals,
Inc. (NASDAQ: ACUR) and King Pharmaceuticals, Inc. (NYSE: KG) today
announced top-line results from Study AP-ADF-111 (Study 111) entitled "A
Phase II, Single-Center, Randomized, Double-Blind, Assessment of the
Abuse Liability of Acurox™ (oxycodone HCl and niacin) Tablets in
Subjects with a History of Opioid Abuse." Study 111 results demonstrate
that Acurox™ Tablets are disliked compared to oxycodone HCl tablets
alone when excess doses are swallowed. These results are statistically
significant based on the dislike/like scores (p = .033), the primary
measure of abuse deterrence potential for the study.
Acurox™ Tablets contain
a unique composition of oxycodone HCl, niacin, and essential functional
inactive ingredients, and are intended to relieve moderate to severe
pain while deterring common methods of prescription drug abuse. King
and Acura entered into a License, Development and Commercialization
Agreement in October 2007. Based on this Agreement, the companies are
jointly developing three immediate-release opioid analgesics using
Acura's patented Aversion® Technology and plan to submit an Acurox™
Tablet New Drug Application (NDA) to the FDA later this year.
About Study 111
Study 111 was a phase II, single-center,
randomized, double-blind, assessment of the abuse liability potential of
Acurox™ (oxycodone HCl/niacin) Tablets in 30 subjects with a history of
opioid abuse. Fasted subjects received a single dose of study drugs
every 48 hours for 9 days and were enrolled in two dosing sequences.
The first dosing sequence (Sequence 1) included randomized doses of (i)
niacin 240mg alone; (ii) a combination of oxycodone HCl 40mg with niacin
240mg (4 times the expected recommended dose of Acurox™ Tablets 5/30mg);
and (iii) placebo tablets. The objective of Sequence 1 was to assess
the effects of oxycodone HCl on the effects of niacin. The second
dosing sequence (Sequence 2) included randomized doses of (i) a
combination of oxycodone HCl 40mg with niacin 240mg (4 times the
expected recommended dose of Acurox™ Tablets 5/30mg) and (ii) oxycodone
HCl 40mg alone. Sequence 2 was designed to assess the abuse liability
and abuse deterrence potential of Acurox™ Tablets versus oxycodone HCl
alone. On each dosing day, vital sign measures and subjective and
behavioral effects were assessed before dosing (baseline) and at 0.5, 1,
1.5, 2, 3, 4, 5, 6, and 12 hours after dosing. Vital signs included
measurement of pupil size, blood pressure, heart rate, oral temperature
and respiratory rate. For both Sequence 1 and Sequence 2, subjective
changes were measured with a two item Drug Rating Questionnaire-Subject
(DRQS) and a 40 item short form of the Addiction Research Center
Inventory (ARCI). The ARCI was comprised of three scale scores
including the Morphine Benzedrine Group scale (MBG) measuring euphoria,
the LSD/dysphoria scale measuring somatic/bodily discomfort and
dysphoria and the Pentobarbital Chlorpromazine Alcohol Group scale (PCAG)
measuring apathetic sedation. For Sequence 2 only, in addition to the
DRQS and ARCI, subjects also completed a Street Value Assessment
Questionnaire and a Treatment Enjoyment Assessment Questionnaire.
Sequence 1 results demonstrated that
response to niacin 240 mg alone compared to placebo causes significant
dislike scores (p = .03), and significant LSD/dysphoria scores (p <
.001) with these negative niacin induced effects manifesting rapidly,
reaching peak at 0.5-1.5 hours and thereafter diminishing. At 0.5 hours
after drug administration, oxycodone HCl 40 mg has limited effect on
niacin-induced disliking and dysphoric effects. At the one hour
observation and afterward, oxycodone may attenuate niacin-induced
disliking and dysphoric effects.
Sequence 2
demonstrated that the
combination of oxycodone HCl 40mg and niacin 240mg (4 times the expected
recommended dose of Acurox™ Tablets 5/30mg) had the potential to be
aversive when compared to oxycodone HCl 40mg alone as shown by
statistically significant and clinically meaningful results in the
dislike/like scores (p = .033), the Treatment Enjoyment Assessment
scores (p = .005) and the LSD/dysphoria scores (p<.001). The
dislike/like score at 0.5 hours was designated the primary measure of
abuse liability and abuse deterrence potential for Acurox™ Tablets
5/30mg and the Treatment Enjoyment Assessment scores and LSD/dysphoria
scores at 0.5 hours were additional measures of the abuse deterrence
potential of Acurox™ Tablets. Subjective measures not achieving
statistical significance included the MBG scores measuring euphoria, the
PCAG score measuring apathetic sedation and the Street Value Assessment
Questionnaire score, in which subjects indicated they would pay more for
oxycodone HCl alone compared to Acurox™ Tablets (p=.097).
In this study of 30
subjects with a history of opioid abuse there were no serious adverse
events reported. Alterations by niacin compared to placebo on vital
signs were minimal and not clinically meaningful. The differences in
vital signs between oxycodone HCl/niacin and niacin alone at 4 times the
expected recommended dose of Acurox™ Tablets were minimal and not
clinically meaningful.
About Prescription Drug
Abuse
The under-treatment of pain is a major
public health issue complicated by abuse of prescription opioids. More
than 75 million Americans suffer from pain, which is more than the
number of people with diabetes, heart disease and cancer combined. While
there are a number of prescription pain medications available, the
increasing misuse, abuse and diversion of prescription pain medications,
especially among young people, is having an impact on physicians’
ability and/or willingness to treat pain using opioid analgesics and is
impeding patient access to these medicines and appropriate care.
According to the National Institute on Drug Abuse, nearly 10 percent of
high school seniors have abused Vicodin®,
a commonly used short acting opioid pain medicine. The increasing
misuse, abuse and diversion of opioid pain medications have become
widespread and pose a costly and significant public health issue in and
of itself. In 2005, the estimated total cost associated with opioid
abuse, including health care, justice, and work-related costs, totaled $9.5 billion.
The pain relief medicines that Acura is developing with King are
designed to address this problem.
About Aversion®
Technology
Opioid pain medicines
developed with Aversion® Technology are intended to relieve
moderate to severe pain while deterring common methods of prescription
drug abuse including, intravenous injection of dissolved tablets, nasal
snorting of crushed tablets and intentional swallowing of excess numbers
of tablets. Tablets or capsules incorporating Aversion® Technology,
when dissolved in water or other common solvents in a volume suitable
for intravenous injection, form a gelatinous mass that increases the
difficulty of chemically extracting oxycodone HCl and creates a physical
impediment to drawing the dissolved drug into a syringe. Products
developed using Aversion® Technology are expected to cause irritation to
the nasal passages when attempts are made to snort crushed tablets.
n addition, products utilizing
Aversion® Technology are designed to cause disliking, bodily discomfort
and dysphoric or unpleasant effects when excess quantities of tablets
are swallowed.
About King
Pharmaceuticals, Inc.
King, headquartered in
Bristol, Tennessee, is a vertically integrated branded pharmaceutical
company. King, an S&P 500 Index company, seeks to capitalize on
opportunities in the pharmaceutical industry through the development,
including in-licensing arrangements and acquisitions, of novel branded
prescription pharmaceutical products in attractive markets and the
strategic acquisition of branded products that can benefit from focused
promotion and marketing and life-cycle management.
About Acura
Pharmaceuticals, Inc.
Acura Pharmaceuticals,
Inc. is a specialty pharmaceutical company engaged in research,
development and manufacture of innovative Aversion® (abuse
deterrent) Technology and related product candidates.
About Forward-looking
Statements
This release contains
forward-looking statements reflecting current views of future events
including, but not limited to, statements pertaining to the expected
timing for submission of the NDA for Acurox™ Tablets with the
FDA; and statements and expectations relating to the potential of Acurox™
Tablets and other Aversion® Technology product candidates.
These forward-looking statements involve certain significant risks and
uncertainties, and actual results may differ materially from the
forward-looking statements. Some important factors which may cause
actual results to differ materially from the forward-looking statements
include dependence on the successful development of Acurox™
and other opioid pain medicines; dependence on King’s and Acura’s
ability to complete clinical and laboratory studies as planned;
dependence on the timely submission of an NDA for Acurox™ with the FDA;
dependence on whether information about the abuse deterrent
characteristics of Aversion® Technology product candidates
are included in the FDA approved label for such products; dependence on
Acura’s and King’s ability to differentiate Aversion®
Technology product candidates from other opioid products based on
information included in the FDA approved label for such products ;
dependence on the companies’ ability to continue to advance the
development of its pipeline products as planned; dependence on the
uncertainty of research, clinical trials, and other development
activities involving pharmaceutical products in which the companies have
an interest; dependence on the unpredictability of the duration and
results of FDA review of Investigational New Drug applications (IND),
NDAs and/or the review of other regulatory agencies worldwide that
relate to products in development; dependence on the availability and
cost of raw materials; dependence on no material interruptions in supply
by contract manufacturers of products in development; dependence on the
affect of the potential development and approval of other new
competitive products; dependence on unexpected adverse side-effects or
inadequate therapeutic efficacy of the companies’ drug candidates that
could slow or prevent product approval or market acceptance (including
the risk that current and past results of clinical trials are not
necessarily indicative of future results of clinical trials). Other
important factors that may cause actual results to differ materially
from the forward-looking statements are discussed in the “Risk Factors”
section and other sections of each of King’s and Acura’s respective Form
10-K for the year ended December 31, 2007 and Form 10-Q for the quarter
ended June 30, 2008, which are on file with the U.S. Securities and
Exchange Commission. The companies do not undertake to publicly update
or revise any of their forward-looking statements even if experience or
future changes show that the indicated results or events will not be
realized.


# # #
EXECUTIVE OFFICES
KING PHARMACEUTICALS,
INC.
501 FIFTH STREET,
BRISTOL, TENNESSEE 37620
ACURA
PHARMACEUTICALS, INC.
616 N. NORTH COURT,
PALATINE, ILLINOIS 60067
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