RespireRx Pharmaceuticals Inc. Announces Preliminary Top-Line
Analysis of Data From Duke University Phase 2A Clinical Trial of
CX1739
RespireRx Reports Safety and Efficacy Data
GLEN ROCK, NJ-(Marketwired - Sep 12, 2016) - RespireRx
Pharmaceuticals Inc. (OTCQB: RSPI) ("RespireRx" or the "Company")
is a leader in the development of medicines for respiratory
disorders, including drug-induced respiratory depression (RD) and
sleep apneas.
RespireRx is today reporting preliminary top-line data from its
Phase 2A clinical trial of CX1739, the Company's proprietary,
orally administered ampakine. CX1739 was determined to be safe and
well tolerated, and antagonized the respiratory depressive effects
of remifentanil (REMI), a potent opioid, in clinical models of
acute opioid overdose and chronic opioid use. These results
demonstrate target engagement of AMPA glutamate receptors and
confirm the Company's translational approach to developing
medicines for respiratory disorders.
The Duke University School of Medicine initiated this
Company-funded Phase 2A clinical trial in March 2016. The dosing
and data accumulation phase of the clinical trial was completed in
June 2016 and the clinical trial was formally completed on July 11,
2016. Database unblinding occurred on September 7, 2016.
Study Design
The clinical trial, conducted in two separate stages over a four
week period, was designed to assess the safety of CX1739, as well
as its ability to antagonize the respiratory depressive effect of
REMI without altering its analgesic properties.
Stage 1, a randomized, double-blind, crossover study comparing
300 mg of CX1739 to placebo, was considered a primary outcome
study. After an overnight stay at the clinical facility, subjects
were administered either placebo or CX1739. For the first visit,
subjects were randomly administered either placebo or 300 mg
CX1739. On the second visit, subjects were crossed over and
administered the other compound.
Three hours after receiving placebo or CX1739, subjects
underwent a REMI 1 period in which respiration was measured by
impedance plethysmography for 5 minutes, in order to establish a
baseline. Subjects then received an intravenous bolus injection of
REMI (1 g/kg) and respiration was measured for an additional 20
minutes after the bolus injections). During REMI 1, the primary
measure used to determine antagonism of respiratory depression was
the calculated time to recover (recovery time - RT) from the
maximal respiratory depressant effects (Emax) of REMI.
Thirty minutes after the bolus injection of REMI, subjects
underwent a REMI 2 period in which a continuous infusion protocol
for REMI was begun (0.25 g /kg bolus followed immediately by a
constant infusion calculated to achieve blood levels of 2 ng/ml).
After allowing 10 minutes for equilibration, respiratory rate, pain
and pupilometry measurements were taken.
REMI 1 was designed as a model of acute opioid overdose, while
REMI 2 was designed as a model of chronic, opioid consumption in
which opioid blood levels remain relatively constant.
The clinical trial also evaluated the safety of CX1739 when
taken alone and in conjunction with REMI and investigated the
effect of CX1739 on the analgesic and sedative effects of REMI.
These latter data have not yet been analyzed and will be reported
at a future date.
Stage 2 took place during the second two week period and was
designed as an open-label, ascending dose study to assess the
ability of 600 and 900 mg of CX1739 to antagonize the respiratory
depressive effects of REMI. Otherwise, Stage 2 was conducted in the
same manner as Stage 1.
Safety and Study Conduct
Twenty-one subjects initially were enrolled in the study and all
were included in the safety analysis. Four subjects terminated
early, two because of scheduling problems and two because of
adverse events (AEs). Of the 17 subjects who completed the study,
two did not display maximal depression of respiration rate (Emax)
>25% and were not included in the respiratory data analyses.
In general, CX1739 was safe and well tolerated, and no serious
adverse events (SAEs) occurred. By far, the most frequent AEs were
nausea, vomiting, headache and dizziness, all of which are common
side effects of opioids. Forty-nine AEs were reported by 15 of the
21 subjects. Thirty-nine AEs occurred after the administration of
REMI and 8 AEs occurred less than one hour after ampakine or
placebo administration, a time period that is too early for
significant blood levels of CX1739 to have occurred.
Efficacy Measures
REMI 1. Acute bolus injection of REMI caused a rapid and
dramatic decline in respiration, with Emax ranging from 15% - 100%
across subjects. When subjects in Stage 1 were pre-treated with 300
mg of CX1739, a statistically significant reduction of RT, the
primary outcome measure, was observed. RT was reduced from a mean
of 6.8+ 0.98 after placebo pre-treatment to a mean of 4.4+0.77
after 300 mg of CX1739 pre-treatment (p=.01, paired t test). In
Stage 2, RT was reduced for both doses, although no significant
differences (p>.05) were observed when these doses were compared
to either placebo or 300 mg. While this difference between 300 mg
and the higher doses might reflect greater efficacy at the 300 mg
dose, the Company believes that this lack of significance for the
higher doses might also reflect inter-subject variability in what
doses produced the optimum decline in RT. Supporting this idea,
responder analysis revealed that decreases in RT were observed, in
a statistically significant proportion of subjects (13 out of 15,
p<.005, z test), after one or more doses of CX1739. Using these
data from optimum doses, mean RT was significantly (p<.002,
paired t test) reduced from 6.8 +0.98 minutes after placebo to 3.7
+0.70 minutes after CX1739.
REMI 2. The REMI 2 period began 30 minutes after the REMI 1
bolus injection of REMI and in this case was a continuous
intravenous infusion. Baseline respiration was recorded during the
first 2 minutes. Ten minutes after REMI 2 began, when respiratory
rates and presumably blood levels of REMI had stabilized,
respiration was monitored continuously for 5 minutes and the
average percentage change from baseline for the 5 minute interval
was determined. The data from 5 subjects was excluded from analysis
because the REMI produced less than 25% depression of respiratory
rate when these subjects were pretreated with placebo. CX1739
produced a dose-related diminution in the respiratory depression
produced by REMI, with statistically significant differences from
placebo observed at 600 mg (p < 0.05, t test) and 900 mg (p =
0.01, t test).
Data regarding CX1739's ability to alter the opioid's analgesic
properties have not yet been analyzed. A full statistical analysis
is expected to be completed during October 2016 and a clinical
study report is expected to be completed by the end of December
2016.
Conclusions
Having demonstrated proof of principle and target engagement,
the Company has concluded that further development of CX1739 to
determine its potential efficacy in the appropriate clinical
indications is warranted, and future studies are being designed and
planned.
About RespireRx Pharmaceuticals Inc.
RespireRx Pharmaceuticals Inc. is a leader in the development of
medicines for respiratory disorders, with a focus on drug-induced
respiratory depression and sleep apneas. The Company holds
exclusive licenses and owns patents and patent applications 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
different 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 being developed by RespireRx is a class
of proprietary compounds known as ampakines, which act to enhance
the actions of the excitatory neurotransmitter glutamate at AMPA
glutamate receptors. Several ampakines, in both oral and injectable
form, 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 damage 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. A second platform being developed by RespireRx is
the class of compounds known as cannabinoids, including, in
particular, dronabinol, a synthetic version of 9-THC
(9-tetrahydrocannabinol). 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
Obstructive Sleep Apnea ("OSA"). The University of Illinois and
three other centers conducted a six week, double-blind, placebo-
controlled Phase 2B clinical trial investigating the effects of
dronabinol in patients with OSA. The University of Illinois has
indicated that recruitment for this clinical trial was completed
during the second quarter of 2016. Final research results are
expected to be announced in the fourth quarter of 2016. This
clinical trial was fully funded by the National Heart, Lung and
Blood Institute of the National Institutes of Health and was
managed by researchers at the University of Illinios.
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 U.S.
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, which
are all considered 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 by management 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 most 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.
Contact Information
Company Contact: Jeff Margolis Vice-President, Treasurer and
Secretary Telephone: (917) 834-7206 E-mail:
jmargolis@respirerx.com
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