RespireRx Pharmaceuticals Inc. Announces Data for CX1739
Clinical Study in Opioid Induced Respiratory Depression
GLEN ROCK, NJ-(Marketwired - Dec 15, 2016) - RespireRx
Pharmaceuticals Inc. (OTCQB: RSPI) ("RespireRx" or the "Company"),
a leader in the development of medicines for respiratory disorders,
including sleep apneas and drug-induced respiratory depression
announces data for its CX1739 clinical study in opioid induced
respiratory depression.
Comments by the Executive Chairman and Chief Scientific
Officer
Arnold Lippa, Ph.D., Executive Chairman and Chief Scientific
Officer commented, "We are pleased with the positive results of our
recent Phase 2A study which encourages us to take CX1739 forward in
additional studies. We look forward to conducting additional
studies investigating the effects of CX1739 on opioid induced
respiratory depression in post-surgical patients self-administering
opioids in a hospital setting as well as on central sleep apnea in
out-patients taking oral opioids chronically for pain
management."
Background
Opioid analgesics are now the most commonly prescribed class of
medicines in the United States, where chronic pain is estimated to
affect around 68 million people each year. In 2014 alone, U.S.
retail pharmacies dispensed 245 million prescriptions for opioid
pain relievers. Opioids are useful and effective analgesics but
produce several unwanted side effects, including episodes of
potentially life-threatening respiratory depression, which resulted
in over 30,000 deaths in 2014. While some of these deaths are from
abuse of opioids, a large number are accidental deaths by patients
who require opioids for pain management, in both an acute and
chronic setting.
The respiratory depression produced by opioids is most
sensitively detected during sleep and is manifested as
apnea/hypopnea or central sleep apnea (CSA). Opioid induced sleep
apneas are observed with intravenous opioid infusions in a
post-surgical hospital setting, where approximately 2 - 4% of the
51 million U.S. patients undergoing in-hospital surgery present
with opioid induced CSA. Furthermore, patients chronically taking
oral opioids for pain relief also present with CSA. In fact,
approximately 40 - 50% of patients diagnosed with CSA are taking
chronic, oral opioids. Overall, sleep apnea is the major risk
factor for mortality and morbidity in opioid overdose. Clearly,
preventing or reducing the respiratory depressive effects of
opioids will save lives.
In short, there is very substantial unmet medical need and very
large market potential in treating respiratory depression/sleep
apnea in patients who require short term or long term treatment
with opioids to manage their pain. CX1739 belongs to a class of
drugs called ampakines that the Company is developing to be taken
in conjunction with opioids in order to reduce respiratory
depression without altering analgesia.
Summary of Clinical Trial Results
In order to understand the relevance of the data in this study,
it is important to understand the conditions under which opioids
are used. The preponderance of opioid use is for the treatment of
pain. Regardless of whether the opioid is taken orally or
intravenously, either acutely or chronically, the treatment of pain
requires stable opioid blood levels that also can produce
respiratory depression/sleep apnea. Alternatively, some opioid
users consume a large acute dose of opioid, whether orally or
intravenously, intentionally or accidentally, that also can produce
potentially fatal respiratory depression. While opioid antagonists,
such as Narcan, are the gold standard for the treatment of acute
opioid overdose, their use is inappropriate for patients taking the
opioids for pain relief because they antagonize the analgesic
effects of the opioids at the same time that they antagonize
respiratory depression.
The recently completed Phase IIa clinical trial evaluated the
ability of CX1739 to overcome the respiratory depression induced by
the powerful, yet short-acting opioid, remifentanil, in two models
of opioid use: During REMI-INFUSION, respiration, pain, and other
parameters were measured during a 30 minute intravenous infusion of
remifentanil in order to produce stable blood levels resulting in
approximately 50% declines in respiratory rate over this period.
During REMI-BOLUS, a model of acute opioid overdose, a single,
intravenous bolus injection of remifentanil was administered at a
dose calculated to achieve approximately 50% respiratory
depression.
During REMI-INFUSION, CX1739 treatment antagonized the
respiratory rate depression produced by remifentanil, with
statistically significant effects observed at 300mg (p < .005)
and 900mg (p < .001). The antagonism produced by the 600mg dose
did not achieve statistical significance. This lack of a linear,
dose response effect is not unusual in early stage clinical trials.
During this period, CX1739 did not significantly alter the
analgesic and sedative effects of reminfentanil.
During REMI-BOLUS, CX1739 treatment did not prevent respiratory
depression, nor improve time to recovery at any of the doses
tested.
Overall, CX1739 was found to be safe and well tolerated, both
prior to and during administration of remifentanil.
Treatment-related adverse events (AEs) for the various doses of
CX1739 were mild, with an incidence comparable to that reported for
placebo. The great majority of AEs occurred after remifentanil
administration.
Description of the Study Design
The study consisted of two separate stages. Stage 1 was a
randomized, double-blind, crossover study comparing 300 mg CX1739
to placebo and Stage 2 was an open-label, ascending dose study to
assess 600 and 900 mg of CX1739. Subjects were tested once a week
over a four-week period. Statistical comparisons were performed for
Stage 1 alone as well as for Stage 1 and Stage 2 combined.
On each study day, REMI-BOLUS was initiated with an intravenous,
bolus injection of remifentanil 3 hours after subjects received
either placebo or CX1739. Respiration was measured for 20 minutes
and then compared to the baseline respiration recorded 5 minutes
prior to the bolus injection. REMI-INFUSION was initiated 3.5 hours
after placebo or CX1739, with an intravenous infusion protocol
designed to maintain stable remifentanil blood levels and
calculated to produce approximately 50% respiratory depression.
The study was conducted at the Duke Clinical Research Unit of
the Duke Clinical Research Institute. The ClinicalTrials.gov
identifier is NCT02735629.
About RespireRx Pharmaceuticals Inc.
RespireRx Pharmaceuticals Inc. is a leader in the development of
medicines for respiratory disorders, with a focus on sleep apneas
and drug-induced respiratory depression. The Company holds
exclusive licenses and owns patents and patent applications or
rights thereto for certain families of chemical compounds that
claim the chemical structures and their uses in the treatment of a
variety of disorders, as well as claims for novel uses of known
drugs.
RespireRx has a pipeline of medicines in Phase 2 clinical
development focused on pharmaceutical treatments for a variety of
breathing disorders. Clinical development in the area of
respiratory disorders, particularly drug-induced respiratory
depression and sleep apnea, has created opportunities for the
development and commercialization of the Company's compounds.
Ampakines. One platform of proprietary medicines being developed
by RespireRx are ampakines, which act to enhance the actions of the
excitatory neurotransmitter glutamate at AMPA glutamate receptors.
Several ampakines, in both oral and injectable forms, are being
developed by the Company for the treatment of a variety of
breathing disorders. In clinical studies, select ampakines have
shown preliminary efficacy in central sleep apnea and in the
control of respiratory depression produced by opioids, without
altering the opioid analgesic effects. In animal models of orphan
disorders, such as Pompe Disease, spinal cord injury and perinatal
respiratory distress, it has been demonstrated that certain
ampakines improve breathing function. The Company's compounds
belong to a new class that does not display the undesirable side
effects previously reported for other ampakines.
Cannabinoids. The other platform being developed by RespireRx is
the class of compounds known as cannabinoids, including dronabinol.
Under a license agreement with the University of Illinois, the
Company has rights to patents claiming the use of cannabinoids for
the treatment of sleep-related breathing disorders. In a
double-blind, placebo-controlled, dose-ascending Phase 2A clinical
study conducted by the Company, dronabinol produced a statistically
significant reduction in the Apnea-Hypopnea Index, the primary
therapeutic end-point, and was observed to be safe and
well-tolerated in a group of patients with OSA.
Additional information about the Company and the matters
discussed herein can be obtained on the Company's web-site at
www.RespireRx.com or in the Company's filings with the Securities
and Exchange Commission at www.sec.gov.
Cautionary Note Regarding Forward-Looking Statements
This press release contains certain forward-looking statements
within the meaning of Section 27A of the Securities Act of 1933 and
Section 21E of the Securities Exchange Act of 1934 and the Company
intends that such forward-looking statements be subject to the safe
harbor created thereby. These might include statements regarding
the Company's financial position, business strategy and other plans
and objectives for future operations, and assumptions and
predictions about research and development efforts, including, but
not limited to, preclinical and clinical research, design,
execution, timing, costs and results, future product demand,
supply, manufacturing, costs, marketing and pricing factors are all
forward-looking statements.
In some cases, forward-looking statements may be identified by
words including "anticipates," "believes," "intends," "estimates,"
"expects," "plans," and similar expressions include, but are not
limited to, statements regarding (i) future research plans,
expenditures and results, (ii) potential collaborative
arrangements, (iii) the potential utility of the Company's proposed
products, and (iv) the need for, and availability of, additional
financing.
The forward-looking statements included herein are based on
current expectations that involve a number of risks and
uncertainties. These forward-looking statements are based on
assumptions regarding the Company's business and technology, which
involve judgments with respect to, among other things, future
scientific, economic and competitive conditions, and future
business decisions, all of which are difficult or impossible to
predict accurately and many of which are beyond the Company's
control. Although the Company believes that the assumptions
underlying the forward-looking statements are reasonable, actual
results may differ materially from those set forth in the
forward-looking statements. In light of the significant
uncertainties inherent in the forward-looking information included
herein, the inclusion of such information should not be regarded as
a representation by the Company or any other person that the
Company's objectives or plans will be achieved.
Factors that could cause or contribute to such differences
include, but are not limited to, regulatory policies or changes
thereto, available cash, research and development results,
competition from other similar businesses, and market and general
economic factors. This press release should be read in conjunction
with the condensed consolidated financial statements (unaudited)
and notes thereto included in Item 1 of the Company's recently
filed Quarterly Report on Form 10-Q and the Company's Annual Report
on Form 10-K for the fiscal year ended December 31, 2015, including
the section entitled "Item 1A. Risk Factors." The Company does not
intend to update or revise any forward-looking statements to
reflect new information, future events or otherwise.
Company Contact: Jeff Margolis Vice-President, Treasurer and
Secretary Telephone: (917) 834-7206 E-mail:
jmargolis@respirerx.com
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