King Pharmaceuticals Showcases Data From Pain Pipeline of Medicines Designed to Deter Common Methods of Non-Therapeutic Use
2009年6月25日 - 10:00PM
PRニュース・ワイアー (英語)
ACUROX(R) and EMBEDA (TM) Data Highlighted at the College on
Problems of Drug Dependence Annual Meeting RENO, Nev., June 25
/PRNewswire/ -- King Pharmaceuticals, Inc. (NYSE:KG) today
announced that the Company is presenting safety and efficacy data
for ACUROX(R) and EMBEDA(TM) (ALO-01), two novel opioid analgesic
formulations that are in development, at the 71st Annual Meeting of
the College on Problems of Drug Dependence. King is also developing
other pain medicines employing unique technology platforms designed
to address risks associated with currently marketed opioids. "We
anticipate that ACUROX(R) and EMBEDA(TM), upon approval, will offer
new therapeutic tools for physicians treating people living with
pain," said Eric Carter, Chief Science Officer of King
Pharmaceuticals. "Our expectation is that these novel technologies
could become instrumental in a physician's arsenal of safe and
effective pain medicines that can help with an overall risk
management plan." Highlights of King's presentations and King
supported presentations are as follows: ACUROX(R) (oxycodone
HCl/niacin) Tablets for the Treatment of Acute, Moderate to Severe
Pain Following Bunionectomy Surgery in Adult Patients ACUROX(R)
Tablets are a unique composition of short-acting oxycodone HCl,
niacin and functional inactive ingredients intended to relieve
moderate to severe pain. A Phase III study evaluated the analgesic
efficacy and safety of ACUROX(R) in adults with moderate to severe
pain following bunionectomy surgery. The 405 participants received
either two ACUROX(R) Tablets 7.5/30 mg, two ACUROX(R) Tablets 5/30
mg or two placebo tablets every six hours for 48 hours after
surgery. Both doses of ACUROX(R) Tablets demonstrated significant
reduction in pain compared to placebo. The adverse event profile
was similar to that seen with short-acting oxycodone, and ACUROX(R)
was generally well tolerated. Evaluation of Plasma Naltrexone
Concentrations Resulting From Use of ALO-01 (morphine sulfate
extended-release with sequestered naltrexone hydrochloride)
Capsules for Chronic Pain EMBEDA(TM) Capsules (ALO-01), a novel
opioid formulation, contain pellets of an extended-release
formulation of morphine sulfate surrounding an inner core of
naltrexone hydrochloride. EMBEDA(TM) is intended to treat moderate
to severe chronic pain. This 12 month open-label safety study
evaluated the plasma concentrations of naltrexone following use of
ALO-01 (morphine sulfate and naltrexone hydrochloride). Samples
were drawn to measure plasma concentrations (concs) of morphine (M)
naltrexone (N) and its metabolite, 6-beta-naltrexol (6-beta-N) when
taken as directed. Results showed that, when ALO-01 was taken as
directed, steady state plasma morphine levels remain stable.
Naltrexone and 6-beta-N do not accumulate; small amounts, when
detected, were not dose related and not associated with clinically
observable effects of opioid withdrawal or reduction of pain
relief. Phase II Study to Evaluate the Dose Response for Flushing,
Safety and Tolerability of Escalating Doses of Niacin in Fasted and
Fed Healthy Adult Volunteers ACUROX(R) Tablets, with Aversion(R)
Technology, are a composition of oxycodone HCl, niacin, and other
inactive ingredients. The niacin ingredient can generate a
temporary, but increasingly unpleasant effect, including flushing.
A Phase II study was conducted to evaluate the dose response for
niacin-induced flushing, the effect of food on niacin-induced
flushing, and the safety and tolerability of varying doses of
niacin. Volunteers were broken into two groups (fed and fasted) and
were provided varying doses of niacin to consume over a period of
days. Results demonstrated a niacin dose-response relationship in
both fed and fasted volunteers, with niacin being better tolerated
in the fed state. Also, the most frequently reported adverse
effects (AEs) were those commonly associated with niacin. These
findings suggest that niacin will be well tolerated up to 60 mg per
dose and will likely be well tolerated at 90 mg per dose. Phase II
Multiple-Dose Study of the Safety and Tolerability of Niacin 30 mg
and 60 mg Combined With Oxycodone HCl 5 mg Versus Oxycodone HCl 5
mg Alone in Healthy Adult Volunteers A Phase II study was conducted
to evaluate the safety and tolerability of multiple daily doses of
the active components of ACUROX(R) Tablets, and to determine if
tolerance to the effects of niacin develops after repeat
administration. Three groups of participants received different
doses of niacin combined with oxycodone HCl, and the Side Effects
and Symptoms Questionnaire (SESQ) and the Niacin Tolerability
Rating Scale (TRS) were used to assess niacin tolerability end
points. Results showed that approximately 75 percent of all
volunteers in all groups rated the tolerability of study drugs as
easy to tolerate or as having no effect, and that adverse effects
(AEs) were consistent with the known safety profiles of oxycodone
and niacin. These findings support the safety and tolerability of
niacin in ACUROX(R) Tablets when taken at the recommended dose. The
Interaction Between Opioids and Alcohol: Results from a Global
Literature Review The potential risk for alcohol to interact with
drugs and/or disrupt a drug formulation matrix is a prevalent
safety concern. For extended-release opioids, there is an added
concern that ethanol (EtOH) may disrupt the formulation mechanism
leading to increased bioavailability of the opioid. Although the
combination of EtOH and prescription opioids is frequently cited as
having increased impairing effects, very few studies have examined
the extent of the pharmacokinetic (PK) and pharmacodynamic (PD)
interaction between them, particularly when taken at therapeutic
doses. A literature review was conducted to gather published data
on the safety risks associated with alcohol-opioid interactions,
alcohol-induced dose-dumping, and the methodology used to
characterize such interactions. The review found that the
combination of EtOH and select opioids at the studied doses does
not appear to produce additive pharmacodynamic effects, while the
pharmacokinetic profiles may be affected for certain other opioids
when combined with EtOH. Additional studies would be required to
further assess and verify these findings About ACUROX(R) Tablets
ACUROX(R) is an investigational patented, orally administered,
immediate release tablet containing oxycodone HCl as its sole
active analgesic ingredient with a proposed indication for the
relief of moderate- to-severe pain. ACUROX(R) utilizes Acura's
proprietary Aversion(R) Technology. Aversion(R) Technology is a
patented triple-action composition of niacin and inactive
ingredients. These ingredients can generate a temporary, unpleasant
effect if orally over-consumed, turn dissolved tablets into a thick
gelatinous mixture making it difficult to draw into a syringe, or
produce a mild burning sensation in the nostrils when crushed and
snorted. There is no evidence that ACUROX(R)'s triple-action
combination of niacin and inactive ingredients reduces its abuse
liability. About EMBEDA(TM) EMBEDA(TM) is an investigational
long-acting opioid analgesic that contains extended-release
morphine pellets, each with a sequestered core of naltrexone, an
opioid antagonist. The formulation is designed to work such that if
taken as directed, the morphine would relieve pain while the
sequestered naltrexone would pass through the body with no intended
clinical effect. If EMBEDA(TM) is crushed or chewed, the naltrexone
would be released, mitigating the euphoric effect of the morphine.
The clinical significance of the degree of these reductions has not
been established and there is no evidence that the naltrexone in
EMBEDA(TM) reduces the abuse liability of EMBEDA(TM). 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
through in-licensing arrangements and acquisitions, of novel
branded prescription pharmaceutical products and technologies that
complement the Company's focus in specialty-driven markets,
particularly neuroscience and hospital. King's wholly-owned
subsidiary, Alpharma, Inc., is also a leader in the development,
registration, manufacture and marketing of pharmaceutical products
for food producing animals. Forward Looking Statements This release
contains forward-looking statements which reflect management's
current views of future events and operations, including, but not
limited to, statements pertaining to King's planned presentations;
statements pertaining to the Company's expectations for its novel
pain treatment candidates and potential prospective physician
utilization of these candidates; and statements pertaining to the
Company's expectations regarding the FDA's review of the Company's
NDAs for Acurox(R) (oxycodone hydrochloride and niacin) tablets and
Embeda(TM). 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 King's ability
to conduct its presentations as planned; dependence on the
Company's ability to continue to advance the development of its
pipeline products as planned; dependence on the high cost and
uncertainty of research, clinical trials, and other development
activities involving products in which King has an interest;
dependence on the unpredictability of the duration and results of
the FDA's review of Investigational New Drug applications ("IND"),
NDAs, and Abbreviated New Drug Applications ("ANDA") and/or the
review of other regulatory agencies worldwide that relate to those
projects; dependence on the availability and cost of raw materials;
dependence on no material interruptions in supply by contract
manufacturers of King's products; dependence on King's compliance
with FDA and other government regulations that relate to the
Company's business; dependence on changes in general economic and
business conditions; changes in current pricing levels; changes in
federal and state laws and regulations; changes in competition;
unexpected changes in technologies and technological advances; and
manufacturing capacity constraints. 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 King's Annual Report on Form 10-K for
the year ended December 31, 2008 and its Quarterly Report on Form
10-Q for the quarter ended March 31, 2009, each of which is on file
with the U.S. Securities and Exchange Commission. King does not
undertake to publicly update or revise any of its forward-looking
statements even if experience or future changes show that the
indicated results or events will not be realized. DATASOURCE: King
Pharmaceuticals, Inc. CONTACT: Media inquiries, Christina Plourde,
+1-202-955-6222, for King Pharmaceuticals; or Investor Relations,
Jack Howarth, +1-908-429-8350
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