Intra-Cellular Therapies Announces the Successful Completion of a Phase Ib/II Study of ITI-007 in Patients with Schizophrenia
NEW YORK, July 29 /PRNewswire/ -- Intra-Cellular Therapies, Inc.
today announced the results from a Phase Ib/II clinical trial in
patients with schizophrenia with ITI-007, the Company's unique,
investigational new drug for the treatment of schizophrenia. The
trial met its primary endpoint demonstrating that ITI-007 was safe
and well-tolerated in patients with stabilized schizophrenia. In
addition, several exploratory endpoints were evaluated. Treatment
with ITI-007 yielded important clinical signs consistent with
antipsychotic and antidepressant efficacy including a reduction in
the total Positive and Negative Syndrome Scale (PANSS) and the
Calgary Depression Scale for Schizophrenia (CDSS). These results
establish a firm basis for selecting an active dose range for
future efficacy trials of ITI-007 in the treatment of patients with
acutely exacerbated schizophrenia.
"New and safer drugs are needed to treat the broad spectrum of
symptoms seen in patients with schizophrenia. ITI-007 represents an
exciting new drug with the potential to treat many of the symptoms
that accompany schizophrenia, some of which have been previously
unaddressed," said Carol Tamminga, M.D., Professor of Psychiatry at
the University of Texas, UT Southwestern Medical Center and leader
in the field of schizophrenia research. "Given the novel
pharmacology of ITI-007, the potential exists to treat different
symptoms by simple dose adjustments as the symptoms of
schizophrenia wax and wane over time. Future clinical trials will
be designed to extend these initial findings and to demonstrate the
unique characteristics of ITI-007."
"We are pleased to have demonstrated such an excellent safety
profile of ITI-007 in our target patient population. The
demonstration of clinical signals across a broad spectrum of
exploratory efficacy measures is also encouraging, especially
considering that these patients had clinically stable symptoms at
study entry," stated Sharon Mates, Chief Executive Officer of
Intra-Cellular Therapies. "We believe that the favorable clinical
profile is consistent with ITI-007's unique pharmacology."
SUMMARY OF ITI-007 PHASE IB/II STUDY RESULTS
The Phase Ib/II study was a randomized, double-blind,
placebo-controlled, multiple ascending dose study designed to
evaluate the safety, tolerability and pharmacokinetic profile of
ITI-007 in patients with stable schizophrenia. Exploratory
endpoints included clinical assessments to evaluate the symptoms of
schizophrenia (PANSS) and symptoms of depression (CDSS). Forty-five
patients were randomized to receive ITI-007 or placebo once daily
for five days. Oral doses of ITI-007 up to and including 140 mg
were found to be safe and well-tolerated with repeated
administration in patients with stable schizophrenia who had been
withdrawn from their previous antipsychotic medications. In an
earlier Phase II sleep efficacy trial, low doses of 1-10 mg ITI-007
were shown to significantly improve sleep in patients with
insomnia. In the present study, patients with schizophrenia also
anecdotally reported improvements in sleep. Even at the highest
doses of ITI-007 tested, all adverse events were mild to moderate.
Notably, there were no extrapyramidal side effects (EPS) and no
cognitive impairment, side effects that are often observed
following treatment with other antipsychotic drugs at high doses.
Total cholesterol and triglyceride levels decreased following
withdrawal from previous antipsychotic drugs and while being
treated with ITI-007. Pharmacokinetic profiles suggest a once-a-day
treatment regimen will be sufficient to achieve significant
efficacy in this patient population.
In the current study, total PANSS scores improved in this
patient population after ITI-007 administration. Furthermore,
patients who had been randomized to ITI-007 also exhibited
improvements in symptoms of depression and sleep. Although the
present study was not powered to demonstrate statistically
significant differences in these outcomes, the clinical signals
elicited by ITI-007 are encouraging and will be evaluated more
fully in future efficacy studies.
A previous study in healthy volunteers demonstrated rapid
engagement of target brain receptors with ITI-007 and long-lasting
brain residency time using positron emission tomography (PET).
ITI-007 also showed dose-related increases in occupancy of target
brain receptors and transporters that are important for
antipsychotic and antidepressant efficacy and for enhancing sleep
maintenance, such as dopamine D2 receptors, serotonin 5-HT2A
receptors, and serotonin transporters.
ABOUT SCHIZOPHRENIA
Schizophrenia is a major neuropsychiatric disorder that affects
over one percent of the world population with an illness that
begins in late adolescence and lasts a lifetime. Its best known
symptoms are "positive symptoms", which include hallucinations and
delusions; but other mental functions are also affected, including
social and motivational skills ("negative symptoms") and cognitive
behaviors, like inattention and poor memory. Current antipsychotics
are effective primarily on reducing positive symptoms but leave
negative and cognitive symptoms untouched. Not only are current
drugs incompletely effective, but they also have limiting side
effects, including troublesome actions on motor function, weight
gain, and metabolic symptoms (diabetes and hyperlipidemia), along
with sedation, constipation, dizziness, and loss of bladder
control. Few people with schizophrenia regain normal psychosocial
function. The medical need in this disease area is enormous.
ABOUT ITI-007
ITI-007 is a unique, orally available, investigational drug
being developed for the treatment of schizophrenia and other
neuropsychiatric diseases such as bipolar disorder, major
depressive disorder, sleep maintenance insomnia, and for insomnia
associated with psychiatric and neurological disorders, such as
depression, post-traumatic stress disorder, traumatic brain injury,
Parkinson's disease, Alzheimer's disease and mild cognitive
impairment.
ITI-007 has a novel combination of pharmacological properties
revealed by CNSProfile(TM) technology that will define the next
generation of antipsychotic drugs. ITI-007 combines potent 5-HT2A
receptor antagonism with cell-type-specific modulation of
phosphoprotein pathways downstream of dopamine receptors. As a
dopamine receptor phosphoprotein modulator (DPPM), ITI-007 has dual
properties, acting as a post-synaptic antagonist and as a
pre-synaptic partial agonist at D2 receptors with
mesolimbic/mesocortical selectivity. ITI-007 also stimulates
phosphorylation of glutamatergic NMDA NR2B receptors, in a
mesolimbic specific manner downstream of D1 receptor intracellular
signaling. This regional selectivity in brain areas thought to
mediate the efficacy of antipsychotic drugs together with a broad
serotonergic, glutamatergic, and dopaminergic approach is expected
to result in superior antipsychotic efficacy for positive, negative
and cognitive symptoms associated with schizophrenia. Also unusual
among antipsychotic drugs is ITI-007's serotonin reuptake
inhibition at clinically relevant doses providing antidepressant
efficacy as well as antipsychotic efficacy. The unique combination
of ITI-007's high-potency blockade of 5-HT2A receptors and DPPM
activity should allow a personalized approach to patient treatment
by making it possible for the first time, to select a clinical dose
capable of saturating 5-HT2A receptors while permitting the
"dialing in" of an optimal amount of dopamine receptor modulation
by simple dose adjustments using a single drug. At low doses,
ITI-007 improves sleep in patients suffering from insomnia
characterized by difficulty maintaining sleep throughout the night,
without producing daytime sedation. In contrast to most other
antipsychotic medications, ITI-007 is non-sedating, increasing
sleep and decreasing wakefulness during the night with no daytime
drowsiness or next-day hangover effects. At higher doses, the
ability to optimize the level of dopamine receptor modulation holds
promise for the reduction of acute as well as chronic psychotic
symptoms in patients with schizophrenia without incurring motor
disturbances and other deleterious side effects. Importantly,
ITI-007 also has a low propensity, much lower than currently
marketed antipsychotic drugs, to bind receptors that mediate
deleterious cardiovascular events, profound sedation and rapid and
significant weight gain. In addition, the wide separation of
affinity at 5-HT2A and D2 receptors may allow for administration of
the appropriate amount of dopamine modulation for antipsychotic
maintenance therapy and the treatment of bipolar disorder,
posttraumatic stress disorder, behavioral disturbances in
Alzheimer's disease, and autism. The serotonin reuptake inhibition
allows for additional antidepressant efficacy for the treatment of
schizoaffective disorder, co-morbid depression, and/or as a
stand-alone treatment for major depressive disorder (MDD).
ABOUT INTRA-CELLULAR THERAPIES
Intra-Cellular Therapies, Inc. (ITI) is a biopharmaceutical
company developing novel drugs for the treatment of diseases and
disorders of the Central Nervous System (CNS). Building on the
science generated from the Nobel Prize winning laboratory of Dr.
Paul Greengard at The Rockefeller University, the Company develops
compounds that have the potential to treat a wide range of diseases
associated with the CNS, including schizophrenia, sleep disorders,
Parkinson's and Alzheimer's diseases, cognitive deficits in
schizophrenia, depression and female sexual dysfunction, and other
disorders pertaining to Women's Health. To aid in the development
process, ITI incorporates its CNSProfile(TM), a state-of-the-art
platform that allows the Company to choose compounds with the
strongest potential to succeed in these difficult to treat
diseases.
ABOUT CNSProfile(TM)
Intra-Cellular Therapies has developed a state-of-the-art
technology platform, called CNSProfile(TM), that is capable of
generating a unique molecular signature for drug compounds.
Specifically, CNSProfile measures the levels of phosphoproteins,
proteins chemically linked at specific sites to phosphates. This
profile provides the Company with a proprietary and unique window
into the intracellular action of CNS drugs or drug candidates. ITI
uses this platform in its drug discovery and development efforts of
proprietary compounds and also to evaluate in-licensing
opportunities.
Source: Intra-Cellular Therapies, Inc.
CONTACT: Allen A. Fienberg, Ph.D. Vice President, Business
Development
of Intra-Cellular Therapies, Inc., +1-212-923-3344; or Rebecca
Birbach
(investors) or Justin Jackson (media) of Burns McClellan,
Inc.,
+1-212-213-0006
Web Site: http://www.intracellulartherapies.com/
Posted: July 2010
