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Wednesday, May 24, 2006 at 12pm EDT
Positive Study Results for DAYTRANA™ (methylphenidate transdermal system)
Presented at a Major Medical Meeting
Philadelphia, US – May 24, 2006 – Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ)
announced that its methylphenidate transdermal system (MTS), DAYTRANA™
demonstrated statistically significant reductions in the symptoms of Attention
Deficit Hyperactivity Disorder (ADHD) and was generally well tolerated in
patients aged 6 to 12 years in four analyses of two clinical trials reported at
a major medical meeting in Toronto.
“Children with ADHD and their caregivers must manage symptom control throughout
the day in a variety of settings, such as the classroom, after-school
activities, or home,” explained clinical trials principal investigator Sharon
Wigal, Ph.D., associate clinical professor of pediatrics at the University of
California Irvine Child Development Center. “These studies document that a
methylphenidate transdermal ‘skin’ patch formulation is an effective, once-daily
ADHD treatment that can result in the improvement of multiple measures of
behavior and classroom performance.”
DAYTRANA was approved by the U.S. Food and Drug Administration (FDA) for
once-daily use to treat Attention Deficit Hyperactivity Disorder (ADHD) in
children aged 6 to 12 years on April 6, 2006. DAYTRANA is the first and only
non-oral medication for ADHD. Shire expects DAYTRANA to be available in
pharmacies in mid 2006.
Data from phase II and phase III clinical trials presented Wednesday in Toronto
demonstrated that DAYTRANA is a generally well-tolerated and effective treatment
for ADHD in children as shown through improvements in the primary and secondary
endpoints analyzed for children treated with DAYTRANA compared to children
treated with placebo.
DAYTRANA was developed by Noven Pharmaceuticals, Inc., and combines the active
ingredient, methylphenidate, with Noven’s patented DOT Matrix transdermal
technology. This transdermal delivery system was designed to provide continuous
medication release throughout the day. The patch is designed to stay on during
the normal daily activities of a child such as swimming, exercising or bathing.
Because DAYTRANA is a patch, physicians can manage the duration of its effect
and potential side effects by having the patient wear the patch for a shorter
time period than the recommended nine hours on a given day. The patch is
available in four dosage strengths – 10 mg, 15 mg, 20 mg and 30 mg – all
designed for nine-hour wear times with 12-hour efficacy.
Phase II Analog Classroom Study
The phase II analog classroom study included 79 children with ADHD. DAYTRANA was
assessed during a nine-hour wear time. The participants treated with DAYTRANA
demonstrated statistically significant improvement based on the primary study
measure, the standard Swanson, Kotkin, Agler, M-Flynn, and Pelham-Deportment (SKAMP-D)
scale, in which higher ratings reflect greater impairment. Overall, participants
using DAYTRANA significantly reduced their SKAMP-D scores to an average of 3.2
points compared to an average score of 8.0 points for those on placebo (P <
.0001) from baseline.
Similarly, the DAYTRANA group significantly reduced their average total scores
on two secondary measures from baseline, the SKAMP-attention subscale and SKAMP
total subscale, to 6.2 and 9.4, respectively, compared to those on placebo,
which had scores of 9.9 and 17.9 (P <.0001 for both). Moreover, when measured at
wear times of 2, 3, 4.5, 6, 7.5 and 9 hours post application, the participants
treated with DAYTRANA had statistically significantly greater changes from the
study start in their average SKAMP-D and average SKAMP-A scores.
Of note, at just two hours after application, 38.0 percent of those treated with
DAYTRANA achieved a 30 percent reduction in their SKAMP-D score, compared to
just 15.2 percent of those treated with a placebo. Similarly, at the same time
point, 40.5 percent of those treated with DAYTRANA achieved a 30 percent
reduction in their SKAMP-A score, compared to just 12.7 percent of those treated
with a placebo.
A second analysis of this classroom study data, also presented at the meeting,
revealed that overall average total scores on the standard Conners’ Parent
Rating Scale-Revised: Short Form (CPRS-R) were significantly lower for those
receiving DAYTRANA, 20.2 points, compared to those on placebo, 35.3 points, (P <
.0001) from baseline. Participants using DAYTRANA also had significantly lower
average scores compared to those on placebo (P < .0001) for all four CPRS-R
subscales: ADHD Index, Oppositional, Hyperactivity, and Cognitive Problems.
Parents completed the CPRS-R at 11 a.m. and 3 p.m. on the last weekend day prior
to all study site visits.
Phase III Study
In a phase III study, investigators randomly placed 270 participants in one of
three treatment groups: a DAYTRANA patch and a placebo capsule, a placebo patch
and an oral extended-release methylphenidate capsule or a placebo patch and
placebo capsule. All of the groups received both a patch and a capsule daily
each morning, but neither the investigators nor the participants knew to which
group a child was assigned until the study ended.
In this study, the DAYTRANA patch – worn for nine hours – reduced the children’s
overall symptoms of ADHD, compared to a placebo (P < .0001), as measured by the
ADHD Rating Scale-IV (ADHD-RS-IV), in which higher scores reflect greater
impairment. By the study’s end, participants’ average ADHD-RS-IV scores declined
24.2 points (-56 percent) from baseline for children treated with DAYTRANA
versus a decline of 10.3 points (-24 percent) for those treated with placebo.
ADHD-RS-IV assesses 18 individual symptoms of ADHD, in which each symptom is
scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe
symptoms). The symptoms are defined by the Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition, Text Revision®, a publication of the APA.
When assessed using the ADHD-RS-IV inattentiveness and hyperactivity/impulsivity
subscales, the participants treated with DAYTRANA had statistically
significantly greater changes from the study start compared to those on placebo
(P < .0001). Also, by the end of the study, 77.6 percent of the DAYTRANA
participants experienced a greater than 30 percent reduction in their total
ADHD-RS-IV scores, compared to just 28.7 percent of those on placebo.
A second analysis presented at the meeting of these data revealed that total
scores on the standard Conners’ Teacher Rating Scale-Revised: Short Form (CTRS-R)
had significantly greater average reductions from the study start for those
receiving methylphenidate transdermal system, 15.3 points, compared to those on
placebo, 5.1 points, (P < .0001). Participants using DAYTRANA also had
significantly lower average scores compared to those on placebo for all four
CTRS-R subscales: ADHD Index (P < .0001), Oppositional (P <.05), Hyperactivity
(P < .001), and Cognitive Problems (P < .01). Teachers completed the CTRS-R at
11 a.m. and 3 p.m. on the last weekend day prior to all study site visits. By
the study end, the DAYTRANA treatment group had statistically significantly
greater changes in their average CTRS-R total scores at both time points,
compared to those treated with placebo (P <.001).
In both the phase II and phase III studies, DAYTRANA was generally well
tolerated during both the dose optimization and double-blind phases. Adverse
events typically were mild to moderate, resolved with continued therapy and were
consistent with known effects of methylphenidate. Common adverse events seen in
clinical trials included: decreased appetite, insomnia, nausea, vomiting, weight
loss, tics, and affect lability (mood swings).
Shire funded these studies.
About DAYTRANA
DAYTRANA is a Schedule II controlled substance. DAYTRANA was generally well
tolerated in clinical studies. As with other products containing methylphenidate
(the active ingredient in methylphenidate transdermal system), common side
effects reported in children who received DAYTRANA were decreased appetite,
insomnia, nausea, vomiting, weight loss, tics, and affect lability (mood
swings).
DAYTRANA should not be used by children allergic to methylphenidate or other
ingredients in DAYTRANA. The patch should be applied daily to clean, dry skin,
which is free of any cuts or irritation. Avoid applying external heat to the
patch. Skin irritation or allergic skin rash may occur.
Methylphenidate should not be taken by children with significant anxiety,
tension, or agitation; glaucoma; tics, Tourette’s syndrome, or family history of
Tourette’s syndrome; or current/recent use of MAO inhibitors (a type of
antidepressant). Abuse of methylphenidate may lead to dependence. Tell your
healthcare professional if your child has had problems with alcohol or drugs or
has had depression, abnormal thoughts/behaviors, visual disturbances, seizures,
high blood pressure, or heart conditions including structural abnormalities.
For Full Prescribing Information on DAYTRANA system, please visit
www.ADHDSupport.com or call Shire Medical Affairs at 1-800-828-2088, option 4.
About ADHD
ADHD affects approximately 7.8 percent of all school-age children, more than 4
million in the United States. ADHD is considered the most commonly diagnosed
psychiatric disorder in children and adolescents. ADHD is a neurological brain
disorder that manifests as a persistent pattern of inattention and/or
hyperactivity-impulsivity that is more frequent and severe than is typically
observed in individuals at a comparable age and maturity. If untreated, ADHD can
acutely affect a child’s life, leading to problems with family members, friends,
sports, after-school activities and academics.
For further information please contact:
Investor Relations Brian Piper +1 484 595 8252
Media Matthew Cabrey +1 484 595 8248
Shire plc
Shire’s strategic goal is to become the leading specialty pharmaceutical company
that focuses on meeting the needs of the specialist physician. Shire focuses its
business on central nervous system, gastrointestinal, general products and human
genetic therapies. The structure is sufficiently flexible to allow Shire to
target new therapeutic areas to the extent opportunities arise through
acquisitions. Shire believes that a carefully selected portfolio of products
with a strategically aligned and relatively small-scale sales force will deliver
strong results.
Shire’s focused strategy is to develop and market products for specialty
physicians. Shire’s in-licensing, merger and acquisition efforts are focused on
products in niche markets with strong intellectual property protection either in
the US or Europe.
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 forwarding-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, Shire plc's results could be materially affected. The
risks and uncertainties include, but are not limited to: risks associated with
the inherent uncertainty of pharmaceutical research, product development,
manufacturing and commercialization; the impact of competitive products,
including, but not limited to, the impact of those on Shire plc's Attention
Deficit and Hyperactivity Disorder ("ADHD") franchise; patents, including but
not limited to, legal challenges relating to Shire plc's ADHD franchise;
government regulation and approval, including but not limited to the expected
product approval dates of SPD503 (ADHD), SPD465 (ADHD), MESAVANCE ™ (SPD476)
(ulcerative colitis), ELAPRASE ™ (I2S) (Hunter syndrome) and NRP104 (ADHD),
including its scheduling classification by the Drug Enforcement Administration
in the United States; Shire plc's ability to benefit from the acquisition of
Transkaryotic Therapies Inc.; Shire plc's ability to secure new products for
commercialization and/or development; and other risks and uncertainties detailed
from time to time in Shire plc's and its predecessor registrant Shire
Pharmaceuticals Group plc's filings with the US Securities and Exchange
Commission, including Shire plc's Annual Report on Form 10-K for the year ended
December 31, 2005.
Poster # NR734
Wednesday, May 24, 2006 at 12:00 PM EST
Attention and Deportment Ratings of Transdermal Methylphenidate in ADHD
Sharon Wigal, PhD, et al.
Poster # NR726
Wednesday, May 24, 2006 at 12:00 PM EST
Parent Rated Effects of Transdermal Methylphenidate in Children with ADHD
John Turnbow, MD, et al.
Poster # NR635
Wednesday, May 24, 2006 at 12:00 PM EST
Parent and Teacher Rated Effects of MTS and OROS Methylphenidate in ADHD
Oscar G. Bukstein, MD, et al.
Poster # NR695
Wednesday, May 24, 2006 at 12:00 PM EST
Clinician Rated Effects of MTS and OROS Methylphenidate in Pediatric ADHD
Raun Melmed, MD, et al.
Daytrana™, Mesavance™ and Elaprase™ are trademarks of companies within the Shire
group.
DOT Matrix is a trademark of Noven Pharmaceuticals, Inc.
Diagnostic and Statistical Manual of Mental Disorders is a registered trademark
of the American Psychiatric Association.
# # #
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Reviewed: 05/2006
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