Shire Reports Positive Signal Finding Study of Investigative Use of Vyvanse® (lisdexamfetamine dimesylate) Capsules CII in Excessive Daytime Sleepiness Model
(Thomson Reuters ONE) -
Shire plans to review development pathways with health authorities
Philadelphia, PA - January 10, 2011 - Shire plc (LSE: SHP, NASDAQ: SHPGY), the
global specialty biopharmaceutical company, today announced results from a study
of Vyvanse(®) (lisdexamfetamine dimesylate), assessing its effect in a model for
Excessive Daytime Sleepiness (EDS). Vyvanse is a prescription medicine
currently approved in the US, Canada and Brazil for the treatment of ADHD.
Vyvanse should only be used to treat ADHD.
In this investigational, single dose, single-site, randomized, placebo- and
active-controlled study, 135 subjects received Vyvanse 20 mg, 50 mg, 70 mg,
placebo or the active comparator (armodafinil 250 mg (NUVIGIL(®))). On the
primary end point, all groups improved objective wakefulness as compared to
placebo (p<0.0001). Additional pre-specified analyses showed that Vyvanse 70
mg demonstrated statistically significant improvement in objective wakefulness
compared to armodafinil. No significant difference was demonstrated between
Vyvanse 50 mg and armodafinil. Vyvanse 20 mg was demonstrated as inferior to
armodafinil. No conclusions of comparability between Vyvanse and armodafinil
can be drawn from this signal finding study. However, based on these findings
Shire plans to review potential development pathways with health authorities for
Vyvanse as a possible EDS treatment option.
Excessive Daytime Sleepiness is a syndrome characterized by persistent
sleepiness. It may be caused by environmental factors (e.g., insufficient sleep
or non-conventional work schedules) or certain medical disorders (e.g.,
narcolepsy).
"It is estimated that several million people in the US are affected by EDS.
Research such as this may provide clinicians with new therapeutic options in the
management of this clinically important symptom," said Dr. Thomas Roth, Division
Head of Sleep Medicine at The Henry Ford Sleep Disorders and Research Center.
"Shire is committed to exploring potential new uses for Vyvanse as a dopamine
modulator," said Jeffrey Jonas, MD, Senior Vice President of Research and
Development for Shire's Specialty Pharmaceuticals business. "We have plans to
review potential development pathways with health authorities for Vyvanse as a
possible EDS treatment option."
Vyvanse is a prescription medicine currently approved in the US for the
treatment of ADHD. Efficacy in ADHD was based on two controlled trials in
children aged 6 to 12, one controlled trial in adolescents aged 13 to 17, and
two controlled trials in adults. Vyvanse should be used as part of a total ADHD
treatment program that may include counseling or other therapies.
Vyvanse is a stimulant medication and federally controlled substance (CII)
because it can be abused or lead to dependence. Keep Vyvanse in a safe place to
prevent misuse and abuse. Selling or giving away Vyvanse may harm others, and is
against the law. Misuse of stimulants may cause sudden death and serious
cardiovascular adverse events.
About This Study
In this study, healthy men aged 18 to 40 underwent one night of sleep
deprivation following blinded randomization, medication administration, and
performance of multiple alertness assessments. This study model is an accepted
simulation of the clinical experience of EDS. Both objective (Maintenance of
Wakefulness Test or MWT) and subjective (Karolinska Sleepiness Scale or KSS)
measures were performed.
Eligible subjects (n=27 per group, 135 total) were equally randomized to Vyvanse
20 mg, 50 mg, or 70 mg, or armodafinil 250 mg (NUVIGIL®) or placebo. The primary
study end point (an objective measure) was the first 'unequivocal sleep
latency', or how long it takes subjects to fall asleep from the start of the
session, as assessed by the MWT. In the MWT, subjects lay reclined in a dark,
quiet room for 30 minutes and were told to stay awake as long as possible while
the length of time until sleep onset occurred was recorded. 'Unequivocal sleep
latency' was defined as the time to the first three consecutive periods of Stage
1 sleep or one period of Stage 2, 3, 4, or REM sleep.
On the primary analysis of MWT, all doses of Vyvanse statistically improved
wakefulness compared to placebo (p<0.0001) as measured by unequivocal sleep
latency during the MWT.
Additional pre-specified analyses demonstrated that armodafinil 250 mg provided
statistically significant improvement in wakefulness versus placebo (p<0.0001).
These analyses also showed statistically significant improvement in wakefulness
with Vyvanse 70 mg versus armodafinil 250 mg (p =0.0351) as measured by MWT, no
significant difference between Vyvanse 50 mg and armodafinil, and Vyvanse 20 mg
as inferior to armodafinil.
The MWT measurements used in the primary analysis were performed every 2 hours
over an 8 hour period (from 24:00 on Day 1 to 08:00 on Day 2). MWT average
unequivocal sleep latency by group (mean ± SD) included Vyvanse 20 mg (23.3 ±
5.7 minutes), Vyvanse 50 mg (27.9 ± 3.3minutes), Vyvanse 70 mg (29.3 ±
2.3minutes), armodafinil 250 mg (27.6 ± 3.3 minutes) and placebo (15.3 ± 5.2
minutes).
Secondary end points included subjects' perception of sleepiness assessed by the
Karolinska Sleepiness Scale (KSS), a nine-point scale where 1 = very alert and
9 = very sleepy. The KSS was collected hourly following medication
administration. Also, subjects' ability to sustain attention was measured by
Psychomotor Vigilance Task (PVT), where subjects respond to a stimulus by
pressing a button as quickly as possible.
On the subjective KSS, Vyvanse 50 mg and 70 mg statistically improved subjective
wakefulness in comparison to the placebo group (p<0.001; LS mean of average KSS
score). Statistical comparisons revealed Vyvanse 50 mg and 70 mg provided a
statistically significant improvement of subjective wakefulness as measured by
KSS compared to armodafinil 250 mg (p=0.0297 and p=0.0004, respectively).
Neither the Vyvanse 20 mg group nor armodafinil 250 mg group showed a
statistically significant difference from the placebo group or each other. On
the PVT, all active treatment groups significantly improved median reaction time
compared to placebo (p<0.0001) with no significant differences between Vyvanse
20 mg, 50 mg, or 70 mg and armodafinil.
Safety findings are limited since subjects were dosed only one time: no
Treatment Emergent Adverse Events (TEAE) were reported as serious or resulted in
study discontinuation. All active treatment groups had more subjects with
adverse events compared to the placebo group (Vyvanse overall, 21%, armodafinil
250 mg, 14.8% vs. placebo, 7.4%). When examined by dose group, 11.1% of subjects
receiving Vyvanse 20 mg, 29.6% of subjects receiving Vyvanse 50 mg, and 18.5% of
subjects receiving Vyvanse 70 mg experienced TEAEs. The only TEAE occurring in
more than 5% of subjects receiving an active treatment was headache [n=6 (7.4%)
all Vyvanse groups, n=2 (7.4%) armodafinil, n=1 (3.7%) placebo]. Modest
increases in mean blood pressure and heart rate were seen, consistent with
results from previous studies and approved product labels.
Shire plans to submit data on this signal finding study of the investigative use
of Vyvanse in Excessive Daytime Sleepiness for possible presentation at upcoming
medical meetings.
"We are encouraged by the positive outcomes in both objective and subjective
measures in this proof of concept study. Confirmation of these results in larger
studies of EDS patients is required, and we have plans to discuss a potential
development program with regulatory authorities," added Jonas.
About Vyvanse( ®)
Vyvanse is a prescription medicine for the treatment of ADHD in children ages 6
to 17 and adults. Vyvanse should be used as part of a total treatment program
that may include counseling or other therapies
IMPORTANT SAFETY INFORMATION
+------------------------------------------------------------------------------+
|Vyvanse is a federally controlled substance (CII) because it can be abused or |
|lead to dependence. Keep Vyvanse in a safe place to prevent misuse and abuse. |
|Selling or giving away Vyvanse may harm others, and is against the law. |
|Vyvanse is a stimulant medication. Misuse of stimulants may cause sudden |
|death and serious cardiovascular adverse events. |
+------------------------------------------------------------------------------+
* Vyvanse should not be taken by patients who have:
Heart disease or hardening of the arteries, moderate to severe high blood
pressure, overactive thyroid gland (hyperthyroidism), glaucoma, agitated
states, a history of drug abuse, taken an anti-depression medicine called a
monoamine oxidase inhibitor (MAOI) within the last 14 days, or sensitivity to,
are allergic to, or had a reaction to other stimulant medicines.
* Vyvanse is a stimulant medicine. The following have been reported with use
of stimulant medicines.
Heart-related problems:
Tell your doctor if you or your child have any heart problems, heart defects,
high blood pressure, or a family history of these problems. Call your doctor
right away if you or your child have any signs of heart problems such as chest
pain, shortness of breath, or fainting while taking Vyvanse.
Mental (Psychiatric) problems:
Tell your doctor about any mental problems you or your child have, or about a
family history of suicide, bipolar illness, or depression. Call your doctor
right away if you or your child have any new or worsening mental symptoms or
problems while taking Vyvanse, especially seeing or hearing things that are not
real, believing things that are not real, or are suspicious.
* Serious side effects have been reported with use of stimulant medicines such
as Vyvanse, including:
* seizures, mainly in patients with a history of seizures
* eyesight changes or blurred vision
* motion and verbal tics. Patients with tics or Tourette's syndrome may
experience a worsening of symptoms while taking Vyvanse.
* slowing of growth. Your child should have his or her height and weight
checked often while taking Vyvanse. The doctor may stop treatment if a
problem is found during these check-ups.
* The most common side effects reported in studies of Vyvanse were:
* upper belly pain * nausea * dry mouth
* dizziness * weight loss * trouble sleeping
* irritability * decreased appetite * vomiting
For additional safety information, please see accompanying Full Prescribing
Information and Medication Guide, including Warning about Potential for Abuse,
and discuss with your doctor.
Vyvanse( ®) is a registered trademark of Shire LLC.
NUVIGIL(®) is a registered trademark of Cephalon, Inc.
For further information please contact
Investor Relations Eric Rojas (erojas(at)shire.com) +1 781 482 0999
Media Jessica Mann (jmann(at)shire.com) +44 1256 894 280
Matthew Cabrey (mcabrey(at)shire.com) +1 484 595 8248
Notes to editors
Phase 2 Trial Design
This Phase 2 trial was a single-site, randomized, double-blind parallel-group,
placebo-and active-controlled signal finding study designed to evaluate Vyvanse
as monotherapy in a clinical model of wakefulness, examining treatment effect in
healthy adult males undergoing acute nocturnal sleep loss. The study enrolled
135 subjects at 1 study center in the U.S. Twenty-seven subjects were randomized
to each of the 5 arms: 20 mg, 50 mg, or 70 mg Vyvanse, 250 mg armodafinil or
placebo on a 1:1:1:1:1 basis. Each subject received their blinded treatment in
the evening on Day 1, and subsequently underwent assessments including MWTs,
PVTs and KSSs.
The primary efficacy analysis was the comparison between each dose of Vyvanse
and placebo on the mean latency to unequivocal sleep using the average of five
MWT sessions performed every 2 hours (from 2400 on Day 1 to 0800 on Day 2).
Secondary efficacy analyses included mean latency to 10 second sleep from the
average of the five MWT sessions; mean score of the KSS of the average postdose
measurements (from 1950 hours [Day 1] to 1050 hours [Day 2]); and the mean score
of the PVT media reaction time of the average postdose measurements (2115 hours
[Day 1] to 0915 hours [Day 2]). For subjects not falling asleep in an MWT
session, the length of the MWT session was recorded as the unequivocal sleep
latency and time to 10-second sleep. Safety assessments included adverse events,
vital signs, and responses to Columbia Suicide Severity Rating Scale (C-SSRS).
Subjects were healthy and were excluded from the trial if they were smokers, had
an average daily caffeine consumption over 400 mg, had irregular sleep-wake
habits, worked irregular hours, variable or night shift work, had a known or
suspected sleep disorder, engaged in recent travel crossing 2 or more time
zones, or previously received Vyvanse ® or armodafinil. Subjects who were
considered a suicide risk were also excluded.
Sleep Disorders Associated with Excessive Daytime Sleepiness
Excessive Daytime Sleepiness (EDS) is a pathological symptom caused by either
environmental factors (eg, insufficient sleep, inadequate sleep hygiene, work
schedule) or a medical disorder such as Hypersomnias of central origin (eg,
narcolepsy, 1 in 2,000 Americans), Circadian rhythm sleep disorders (eg, shift
work sleep disorder, 25% of 15 million night or shift workers) and sleep-related
breathing disorders (eg, obstructive sleep apnea, 18 million suffers with ~10%
receiving treatment). Collectively, the market for branded drugs to manage these
types of conditions is estimated to be $1 billion.
SHIRE PLC
Shire's strategic goal is to become the leading specialty biopharmaceutical
company that focuses on meeting the needs of the specialist physician. Shire
focuses its business on attention deficit hyperactivity disorder (ADHD), human
genetic therapies (HGT) and gastrointestinal (GI) diseases as well as
opportunities in other therapeutic areas to the extent they arise through
acquisitions. Shire's in-licensing, merger and acquisition efforts are focused
on products in specialist markets with strong intellectual property protection
and global rights. Shire believes that a carefully selected and balanced
portfolio of products with strategically aligned and relatively small-scale
sales forces will deliver strong results.
For further information on Shire, please visit the Company's website:
www.shire.com.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF
1995
Statements included herein that are not historical facts are forward-looking
statements. Such forward-looking statements involve a number of risks and
uncertainties and are subject to change at any time. In the event such risks or
uncertainties materialize, the Company's results could be materially adversely
affected. The risks and uncertainties include, but are not limited to, risks
associated with: the inherent uncertainty of research, development, approval,
reimbursement, manufacturing and commercialization of the Company's Specialty
Pharmaceutical and Human Genetic Therapies products, as well as the ability to
secure and integrate new products for commercialization and/or development;
government regulation of the Company's products; the Company's ability to
manufacture its products in sufficient quantities to meet demand; the impact of
competitive therapies on the Company's products; the Company's ability to
register, maintain and enforce patents and other intellectual property rights
relating to its products; the Company's ability to obtain and maintain
government and other third-party reimbursement for its products; and other risks
and uncertainties detailed from time to time in the Company's filings with the
Securities and Exchange Commission.
# # #
This announcement is distributed by Thomson Reuters on behalf of
Thomson Reuters clients. The owner of this announcement warrants that:
(i) the releases contained herein are protected by copyright and
other applicable laws; and
(ii) they are solely responsible for the content, accuracy and
originality of the information contained therein.
Source: Shire plc via Thomson Reuters ONE
[HUG#1478412]
Unternehmensinformation / Kurzprofil:
Datum: 10.01.2011 - 15:00 Uhr
Sprache: Deutsch
News-ID 50321
Anzahl Zeichen: 18753
contact information:
Town:
Jersey
Kategorie:
Business News
Diese Pressemitteilung wurde bisher 201 mal aufgerufen.
Die Pressemitteilung mit dem Titel:
"Shire Reports Positive Signal Finding Study of Investigative Use of Vyvanse® (lisdexamfetamine dimesylate) Capsules CII in Excessive Daytime Sleepiness Model"
steht unter der journalistisch-redaktionellen Verantwortung von
Shire plc (Nachricht senden)
Beachten Sie bitte die weiteren Informationen zum Haftungsauschluß (gemäß TMG - TeleMedianGesetz) und dem Datenschutz (gemäß der DSGVO).
