UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
WASHINGTON,
D. C. 20549
FORM
8-K
CURRENT
REPORT
Pursuant
to Section 13 or 15(d) of the
Securities
Exchange Act Of 1934
Date
of
Report (Date of earliest event reported)
___________________________________________________________
ACURA
PHARMACEUTICALS, INC.
(Exact
Name of Registrant as Specified in Charter)
___________________________________________________________
|
State
of New York
|
1-10113
|
11-0853640
|
|
(State
of Other Jurisdiction
|
(Commission
File Number)
|
(I.R.S.
Employer
|
|
of
Incorporation)
|
Identification
Number)
|
616
N. North Court, Suite 120
Palatine,
Illinois 60067
(Address
of principal executive offices) (Zip Code)
(847)
705-7709
(Registrant’s
telephone number, including area code)
Check
the
appropriate box below if the Form 8-K filing is intended to simultaneously
satisfy the filing obligation of the registrant under any of the following
provisions (see General Instruction A.2. below):
o
Written
communications pursuant to Rule 425 under the Securities Act (17 CFR
230.425)
o
Soliciting
material pursuant to Rule 14a-12 under the Exchange Act (17CFR
240.14a-12)
o
Pre-commencement
communications pursuant to Rule 14d-2(b) under the Exchange Act
(17CFR240.14d-2(b))
o
Pre-commencement
communications pursuant to Rule 13e-4(c) under the Exchange Act (17CFR
240.13e- 4(c))
Item
8.01 Other
Events
On
March
15,
2007,
the
Registrant issued a press release updating its OxyADF tablets development
program and results of Study AP-ADF-102. A copy of the press release is attached
as Exhibit 99.1 hereto.
Item
9.01 Financial
Statements and Exhibits.
|
Exhibit
Number
|
Description |
|
99.1
|
Press
Release dated March
15, 2007
Updating OxyADF Tablets Development Program and Results of Study
AP-ADF-102.
|
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the registrant
has
duly caused this report to be signed on its behalf by the undersigned thereunto
duly authorized.
| ACURA PHARMACEUTICALS, INC. | ||
| |
|
|
| By: | /s/ Peter A. Clemens | |
|
Peter A. Clemens |
||
| Senior Vice President & Chief Financial Officer | ||
| Date: March 15, 2007 | ||
EXHIBIT
INDEX
|
Exhibit
Number
|
Description |
|
99.1
|
Press
Release dated March
15, 2007
Updating OxyADF Tablets Development Program and Results of Study
AP-ADF-102
|
CONTACT:
Acura
Pharmaceuticals, Inc.,
Investor
Relations, Peter A. Clemens, SVP & CFO 847-705-7709
FOR
IMMEDIATE RELEASE
ACURA
PHARMACEUTICALS, INC. UPDATES OxyADF TABLETS
DEVELOPMENT
PROGRAM AND RESULTS OF STUDY AP-ADF-102
Palatine,
IL, March 15, 2007:
Acura
Pharmaceuticals, Inc. (OTC.BB-ACUR), today announced results of Study AP-ADF-102
("Study 102") a phase II clinical trial for OxyADF
(oxycodone HCl and niacin) Tablets,
the
Company’s lead product candidate incorporating its proprietary Aversion® (abuse
deterrent) Technology. OxyADF Tablets are being developed pursuant to an
investigational new drug application ("IND") on file with the U.S. Food and
Drug
Administration ("FDA") with an intended indication for treatment of moderate
to
moderately severe pain. The
Company also provided a status update on the overall OxyADF Tablets development
program and its proprietary Aversion® (abuse deterrent) Technology.
Study
102 Design, Methodology and Hypothesis
Study
102
is titled, "A Phase II Single-Center, Randomized, Double-Blind Study in Subjects
with a History of Opioid Abuse to Evaluate the Dose-Response for Flushing and
Safety and Tolerability of Varying Doses of Niacin in Combination with 40mg
of
an Opioid vs. 40 mg of an Opioid Alone."
This
was
a placebo-controlled, five-period crossover clinical study conducted on an
inpatient basis with 5 cohorts of 5 subjects each. Twenty-four subjects
completed the study. All subjects received a single dose of study drug (niacin
and oxycodone or oxycodone alone) every 48 hours for 9 days. Each subject,
while
fasted, was administered a random dosing sequence that included three different
dose levels of niacin in combination with 40 mg of oxycodone HCl and 40 mg
oxycodone HCl alone. On the final day of the study, the highest niacin dose
in
combination with 40 mg oxycodone HCl was administered following a standardized
high-fat meal. Vital sign measures and subjective and behavioral effects were
assessed before each dose and at specified time intervals for up to 12 hours
after dosing. Subjective changes were measured by subject response to a Drug
Rating Questionnaire, a Treatment Enjoyment Questionnaire and related subjective
scales. The hypothesis for the study was that the addition of niacin to
oxycodone would produce effects that are disliked by subjects with a history
of
opioid abuse. The maximum scale response (as measured by the subjects) to the
question “Do you dislike the drug effect you are feeling now?” (i.e. the
"Disliking Score"), was designated as the primary efficacy variable. Statistical
analysis (maximum dislike response in comparison to 0 mg niacin) was conducted
for the Drug Rating Questionnaire for all fasted and fed doses of study
drugs.
Study
102 Summary Results
Study
102
demonstrated that in the fasting state, all three dose levels of niacin in
combination with 40mg of oxycodone produced significant disliking scores (p=.05,
p=.01, p=.00 as the niacin dose increased). In the fed state, the high fat
meal
eliminated the niacin induced disliking effect and delayed the time to peak
blood level for oxycodone. No other subjective measure was significantly
affected by the niacin. No serious adverse events were reported. The study
results for the Drug Rating Scale demonstrate that niacin alters the subjective
response to oxycodone as indicated by the statistically significant responses
on
the disliking scale. This observation in conjunction with the results from
the
Treatment Enjoyment Questionnaire indicates that the addition of niacin to
oxycodone reduces the attractiveness of oxycodone to opiate
abusers.
Study
102 Conclusions
The
conclusion from Study 102 supports the hypothesis that the addition of niacin
to
oxycodone in a minimal ratio of 30 mg niacin to 5 mg oxycodone is aversive
when
compared to oxycodone alone and the addition of niacin to oxycodone does not
alter the safety profile of oxycodone alone in subjects with a history of opioid
abuse. The Company intends to include the data and results from Study-102 in
its
505(b)(2) NDA submission for OxyADF Tablets. You are encouraged to review a
more
detailed summary of Study AP-ADF-102 included in the Company's 2006 SEC Form
10K.
Development
Program for OxyADF Tablets
The
technical and pre-clinical development program and regulatory strategy and
status for OxyADF Tablets are summarized below. At this stage, we can not
provide any assurance that FDA will not require additional pre-clinical studies
not listed below, or revise the OxyADF Tablets regulatory requirements prior
to
their acceptance for filing of a 505(b)(2) NDA submission for OxyADF
Tablets.
|
Technical
and Pre-Clinical Development
|
Status
|
|
Formulation
development
|
Complete
|
|
Pilot
bioequivalence study
|
Complete
|
|
Pivotal
oxycodone HCl extraction study
|
Complete
|
|
Tablet
stability for NDA submission
|
Testing
in process. 18 month real time data demonstrates stability acceptable
for
NDA submission
|
|
Toxicology
studies
|
Not
required per FDA written guidance to the
Company
|
|
Regulatory
Affairs
|
Status
|
|
Investigational
New Drug Application
|
Active
|
|
End
of Phase II meeting with FDA
|
Complete
|
|
Factorial
design clinical studies
|
Not
required per FDA written guidance to Company
|
|
Product
labeling
|
Strategy
and concepts discussed with FDA. Written guidance provided by FDA
to the
Company
|
|
Regulatory
submission for commercial distribution in the U.S.
|
OxyADF
Tablets are eligible for submission as a 505(b)(2) NDA per FDA written
guidance to Company
|
|
Phase
III pivotal clinical trial
|
Only
one phase III efficacy and safety trial is required per FDA written
guidance to Company
|
The
clinical development program for OxyADF Tablets is summarized below. At this
stage, the Company cannot provide any assurance
that FDA will not require additional clinical studies prior to their acceptance
for filing of a 505(b)(2) NDA submission for OxyADF Tablets.
|
Clinical
Study Number
|
Phase
I Clinical Study Description
|
Status
|
|
AP-ADF-101
|
Evaluate
optimal amount of niacin per tablet
|
Final
study report complete
|
|
AP-ADF-104
|
Bioequivalence
to non-Aversion®
Technology Reference Listed Drug
|
Final
study report complete. OxyADF tablets are bioequivalent to reference
listed drug
|
|
AP-ADF-106
|
Evaluate
effects of nasal snorting
|
Received
FDA written guidance for protocol design
|
|
AP-ADF-108
|
Single
dose pharmacokinetics
(dose
linearity
and food effect)
|
Received
FDA written guidance for protocol design
|
|
AP-ADF-109
|
Multi-dose
pharmacokinetics (dose linearity)
|
Received
FDA written guidance for protocol design
|
|
AP-ADF-110
|
Single
dose pharmacokinetics and bioavailability. Not required if there
is dose
linearity
|
Received
initial FDA written guidance for protocol
design
|
|
Clinical
Study Number
|
Phase
II and III Clinical Study Description
|
Status
|
|
AP-ADF-102
|
Relative
likeability in subjects with a history of opioid abuse
|
Subject
enrollment complete. Principal Investigator's report and data analysis
complete. Final study report in progress
|
|
AP-ADF-103
|
Repeat
dose safety and tolerability study in normal subjects
|
Final
study report complete
|
|
AP-ADF-107
|
Niacin
dose-response safety and tolerability in normal subjects
|
Subject
enrollment complete. Summary study report complete. Final study report
drafted
|
|
AP-ADF-105
|
Pivotal
Phase III efficacy and safety
|
Received
FDA written guidance for protocol design. Special Protocol Assessment
requested.
|
Additional
OxyADF Tablets Clinical
Studies
Planned
The
FDA
has requested that the Company complete certain additional clinical studies
for
OxyADF Tablets prior to accepting our 505(b)(2) NDA submission including the
following:
Study
AP-ADF-105.
This
study is titled “A Phase III, Randomized, Double-blind, Placebo-controlled,
Multicenter, Repeat-dose Study of the Safety and Efficacy of OxyADF (oxycodone
HCl and niacin) Tablets versus Placebo for the Treatment of Acute, Moderate
to
Severe Postoperative Pain Following Bunionectomy Surgery in Adult Patients.”
This phase III study is planned to enroll approximately 400 patients with
moderate to severe pain following bunionectomy surgery. The
Company has submitted the study protocol to the FDA and requested a Special
Protocol Assessment (SPA). Clinical protocols for Phase III trials which data
will form the primary basis for an efficacy claim are eligible for a SPA. A
SPA
from the FDA is an agreement that the Phase III trial protocol design, clinical
endpoints, and statistical analyses plan are acceptable to support regulatory
approval. A SPA is binding upon the FDA unless a substantial scientific issue
essential to determining safety or efficacy is identified after the testing
is
begun. The Company believes the completion of Study AP-ADF-105 is the critical
time and events path to 505(b)(2) NDA submission for OxyADF
Tablets.
Study
AP-ADF-106.
This
will be a phase I clinical study, for use in product labeling, evaluating the
nasal irritating characteristics of crushed OxyADF Tablets (with and/or without
oxycodone HCl) anticipated to enroll 12-24 normal subjects.
Studies
AP-ADF-108, AP-ADF-109, and if necessary AP-ADF-110. These
will be phase I single dose or multi-dose pharmacokinetic studies anticipated
to
enroll approximately 25-50 normal subjects per study.
Estimated
Timing for submission of a
505(b)(2) NDA for OxyADF Tablets
Estimating
the dates of initiation and completion of clinical studies and the costs to
complete development of the Company's product candidates, including OxyADF
Tablets, would be speculative and potentially misleading. The Company expects
to
reassess its future research and development plans pending review of data
received from development activities currently in progress and the availability
of cash resources to fund such development activities. The cost and pace of
future research and development activities are linked and subject to change.
At
this stage there can be no assurance that any of the Company’s research and
development efforts, including those for OxyADF Tablets, will lead to a
505(b)(2) NDA submission or that if NDA submissions are made with the FDA,
that
any such submission will be accepted for filing or approved by the
FDA.
Product
Candidates in Development using Aversion® Technology
Aversion®
(abuse deterrent) Technology can be formulated into orally administered tablets
or capsules containing active pharmaceutical ingredients including oxycodone,
hydrocodone, hydromorphone, oxymorphone, morphine, codeine, tramadol,
propoxyphene, and other potentially abuseable drugs. In addition to the active
ingredient, Aversion® Technology utilizes certain proprietary combinations of
pharmaceutical product inactive excipients and active ingredients intended
to
discourage or deter pharmaceutical product abuse. Aversion® Technology does
not
utilize
opioid antagonists such as naltrexone and naloxone, bittering agents or dyes.
Provided product candidates pursued
in
development prove successful in laboratory testing and clinical trials, of
which
no assurance can be given, the Company believes that its Aversion® Technology
will discourage the three most common methods of opioid pharmaceutical product
abuse, including (i) intravenous injection of dissolved tablets or capsules,
(ii) nasal snorting of crushed tablets or capsules and (iii) intentional
swallowing of excessive numbers of tablets or capsules.
OxyADF
(oxycodone HCl and niacin) Tablets, is the Company’s lead product candidate with
Aversion® (abuse deterrent) Technology. In
addition to OxyADF Tablets, the Company is also engaged in the formulation
development of additional product candidates
intended
for oral administration
incorporating Aversion® Technology,
including hydrocodone bitartrate with acetaminophen tablets (marketed
generically and under the brand names Vicodin®, Lortab®, and Lorcet®),
hydromorphone
HCl tablets (marketed generically and under the brand name Dilaudid®) and
oxycodone HCl with acetaminophen (marketed
generically and under the brand names of Percocet®, Tylox®, Endocet®,
and
Roxicet®).
These
additional product candidates are in the formulation stage of development.
No
assurance can be provided that such development efforts will lead to product
candidates for which an IND or NDA submission to the FDA will result or that
we
will have sufficient cash reserves or sources of financing to fund the continued
development of such product candidates.
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.
Forward
Looking Statements
This
press release contains "forward-looking statements" as defined in the Private
Securities Litigation Reform Act of 1995. These statements are based on current
expectations of future events. If underlying assumptions prove inaccurate or
unknown risks or uncertainties materialize, actual results could vary materially
from the Company’s expectations and projections. The most significant of such
risks and uncertainties include, but are not limited to, the Company’s ability
to secure additional financing to fund continued operations, the Company’s
ability to enter into contractual arrangements with qualified pharmaceutical
partners to license, develop and commercialize the Company’s technology and
product candidates, the Company’s ability to avoid infringement of patents,
trademarks and other proprietary rights or trade secrets of third parties,
and
the Company’s ability to fulfill the FDA’s requirements for approving the
Company’s product candidates for commercial distribution in the United States,
including, without limitation, the adequacy of the results of the clinical
studies completed to date and the results of other clinical studies, to support
FDA approval of the Company’s product candidates, the adequacy of the
development program for the Company’s product candidates, changes in regulatory
requirements, adverse safety findings relating to the Company’s product
candidates, the risk that the FDA may not agree with the Company’s analysis of
its clinical studies and may evaluate the results of these studies by different
methods or conclude that the results of the studies are not statistically
significant, clinically meaningful or that there were human errors in the
conduct of the studies or otherwise, the risk that further studies of the
Company’s product candidates are not positive, and the uncertainties inherent in
scientific research, drug development, clinical trials and the regulatory
approval process. You are encouraged to review other important risk factors
relating to the Company on our web site at www.acurapharm.com under the link,
“Company Risk Factors” and detailed in Company filings with the Securities and
Exchange Commission. The Company is at development stage and may never have
any
products or technologies that generate revenue. Acura Pharmaceuticals, Inc.
assumes no obligation to update any forward-looking statements as a result
of
new information or future events or developments. All Acura Pharmaceuticals,
Inc. press releases may be reviewed at www.acurapharm.com.