Data Presented as Poster Presentation at the Associated Professional Sleep Societies 2008 Annual Meeting BALTIMORE, June 11
BALTIMORE, June 11 /PRNewswire/ -- Data was presented today at the 22nd
Annual Meeting of the Associated Professional Sleep Societies (APSS)
demonstrating that within 20 minutes of administration, Intermezzo(R), an
investigational low-dose, sublingual formulation of zolpidem, delivered
overall bioavailability that was significantly greater than that produced by a
swallowed Ambien(R) tablet containing a zolpidem dose that was nearly 3 times
higher. Despite this higher initial bioavailability, zolpidem blood levels
from sublingual 3.5 mg Intermezzo(R) were significantly lower four hours after
administration than the levels produced by the 10 mg Ambien(R) dose.
Transcept Pharmaceuticals is developing Intermezzo(R) for the treatment of
insomnia characterized by middle-of-the-night (MOTN) awakenings with
difficulty returning to sleep.
"One significant challenge in trying to help insomnia patients return to
sleep after a middle-of-the-night awakening is that the most commonly
prescribed bedtime medications are not designed to be taken as needed in the
middle of the night without risking significant drowsiness the following day,"
said Thomas Roth, Ph.D., Chief of Sleep Medicine, Henry Ford Hospital Sleep
Disorders and Research Center in Detroit and principal investigator in this
study. "The only recourse to date for patients has been either to try to
predict what nights they will awaken, or to take sleep medication every night
at bedtime. Studies of Intermezzo(R) show promise in offering the first
viable, 'use only when needed' option for treating awakenings in the middle of
the night when they occur."
Intermezzo(R): Rapid bioavailability despite a lower dose
In the pharmacokinetic comparison study presented at APSS, 36 healthy
subjects between the ages of 19 and 64 were randomized to receive either a
3.5 mg. Intermezzo(R) sublingual lozenge or a 10 mg. Ambien(R) tablet
following an overnight fast. Bioavailability assessments began prior to
dosing and continued for eight hours. Although Ambien(R) doses were
approximately three times higher than those of Intermezzo(R), overall
bioavailability at 5 minutes, 10 minutes and 20-minutes was significantly
higher for Intermezzo 3.5 mg compared to Ambien(R) 10 mg. In a previous
clinical sleep laboratory study, Intermezzo(R) 1.75 mg and 3.5 mg demonstrated
a statistically significant improvement in latency to sleep onset vs. placebo;
these are the lowest doses of zolpidem ever shown to be statistically
effective vs. placebo in inducing sleep.
Another of the study's authors, Andrew Krystal, M.D., Associate Professor
and Director of the Duke Clinic Sleep Laboratory, commented, "The
Intermezzo(R) sublingual delivery system appears to markedly increase the
early uptake of zolpidem. Combining early bioavailability with a low dose may
offer patients who wake up in the middle of the night help in returning to
sleep while potentially avoiding next day residual effects."
MOTN Awakenings: Redefining Insomnia
Middle-of-the-night (MOTN) or nocturnal awakenings have been reported to
be one of the most common sleep problems, affecting approximately one-third of
the adult population. According to a recent epidemiological study ("Nocturnal
awakenings and comorbid disorders in the American general population" --
Journal of Psychiatric Research [in press], Maurice M. Ohayon, MD, DSc, PhD.),
nocturnal awakenings are the most frequently reported insomnia symptom in the
general population, with 35 percent of Americans experiencing awakenings at
least three times per week and 23 percent waking up at least once every night.
Ninety percent of the MOTN insomnia population report that their pattern of
awakenings persists for at least six months and 50 percent report such
insomnia problems lasting more than 5 years. Currently, there is no approved
PRN ("use only when needed") treatment for MOTN insomnia.
"The prevalence and impact of nocturnal awakenings may require significant
adjustments in how we define, diagnose and treat insomnia, which is currently
approached in a one-size-fits-all fashion due to the limitations of available
therapies," said Dr. Roth, who participated in a June 2008 APSS symposium
convened to discuss the prevalence and consequences of nocturnal awakenings.
A Potential New Approach for Patients with Middle of the Night Awakenings
In a related APSS poster presentation, investigators described a study in
which they sought to quantify the proportion of MOTN insomnia patients who
would be suitable candidates for treatment with a rapidly effective and
short-acting agent. Investigators monitored 654 patients participating in an
insomnia clinical trial using an Interactive Voice Response System (IVRS) that
patients called each night after a middle of the night awakening. This system
tracked the time of awakenings and amount of bedtime remaining.
Of the original group, 300 met the study criteria and were verified to
suffer from MOTN awakenings with difficulty returning to sleep. These patients
experienced a weekly average of 5.2 such awakenings and more than 90 percent
of these awakenings occurred with at least four hours of bedtime remaining.
"Nearly all patients in this study experienced frequent awakenings at a
time of night when they had at least four hours of sleep remaining. Thus,
they would be appropriate candidates for treatment with a rapid-acting,
low-dose medication," said Russell Rosenberg, Ph.D., principal study author
and Director, NeuroTrials Research and the Atlanta School of Sleep Medicine.
"The study underscored the potential for Intermezzo(R) to be useful in a
patient population such as this."
About Zolpidem
To date, zolpidem has been available in the United States as the active
agent in Ambien(R) and Ambien CRTM, prescribed for adults at 10 mg and 12.5 mg
doses respectively. These amounts are between three and four times the
highest Intermezzo(R) dose available.
It is estimated that over 15 billion doses of zolpidem have been
prescribed since its original approval by the FDA. Zolpidem has been shown to
be safe and effective for the treatment of insomnia, but the high dose
products available in the U.S. and elsewhere have been designed to produce 6
to 8 hours of sleep, and are thus unsuitable for "as needed" treatment of
patients who awaken in the middle of the night and have fewer hours remaining
before waking up in the morning.
About Intermezzo(R)
Intermezzo(R) (zolpidem tartrate sublingual lozenge) employs Transcept
Pharmaceuticals' proprietary Bimucoral(R) technology in a mint-flavored,
sublingual lozenge formulated to dissolve under the tongue in approximately
two minutes. This novel approach has been shown to accelerate the
bioavailability of zolpidem, despite the substantially lower Intermezzo(R)
dose vs. the doses employed with previously available forms of the drug.
About Transcept Pharmaceuticals
Transcept Pharmaceuticals, Inc. is a specialty pharmaceutical company
deriving significant new patient benefits from proven CNS drugs. Transcept
development projects leverage new understanding of CNS conditions to provide
additional uses and enhanced clinical benefits for existing active agents. The
lead Transcept product candidate, Intermezzo(R) (zolpidem tartrate sublingual
lozenge), is a low dose formulation of zolpidem for the treatment of insomnia
in patients who awaken in the middle of the night and have difficulty
returning to sleep. Phase 3 clinical trials have been completed for
Intermezzo(R) and Transcept plans to submit an NDA in the third quarter of
2008. Transcept is also developing TO-2060, a novel, fixed-dose combination of
olanzapine and ondansetron for the treatment of dopamine associated
psychiatric disorders. For further information, please visit the company's
website at: http://www.transcept.com.
Contacts:
The Ruth Group
Transcept Pharmaceuticals, Inc. Investors / Media
Michael Gill Stephanie Carrington / Jason Rando
Director of Communications(646) 536-7017 / 7025
(510) 215-3575scarrington@theruthgroup.com
jrando@theruthgroup.com
SOURCE Transcept Pharmaceuticals, Inc.
