Medeva Pharmaceuticals has reported that results from a Phase III clinical
trial of a modified release formulation of methylphenidate hydrochloride for
the treatment of attention deficit hyperactivity disorder (ADHD) were
presented in abstract form at the 47th annual American Academy of Child and
Adolescent Psychiatry (AACAP) meeting in New York City.
Methylphenidate modified release capsules, which are currently under
review for marketing approval by the U.S. Food and Drug Administration (FDA),
includes a new and unique biphasic release profile which is designed to
eliminate the need for a school day dose. Methylphenidate modified release
capsules utilize Eurand's novel Diffucaps(R) technology, a multi-particulate
bead delivery system with each bead acting as a drug reservoir. Each bead is
coated with a carefully chosen polymer to provide a unique release profile.
Customized release profiles can then be achieved by incorporating different
types of beads into each capsule. Methylphenidate modified release capsules
contain immediate-release and extended-release beads in a ratio of 30 to 70.
Three hundred and fourteen children with ADHD between the ages of six and
15 were evaluated in a randomized, double-blind, parallel-group,
placebo-controlled, 32-center study. The study was comprised of a one-week,
single-blind, placebo run-in and a three-week, double-blind titration and
treatment period. Methylphenidate modified release capsules were given in
individually titrated doses of 20, 40 or 60 mg daily with matching placebo.
The primary objective of the study was to compare the efficacy, safety and
tolerability of once daily (before school) administration of methylphenidate
modified release capsules with placebo in children with a confirmed diagnosis
"The results of this trial demonstrate that methylphenidate modified
release capsules given once daily before school, were shown to control the
symptoms of ADHD throughout the school day without the need for a second
midday dose," said Laurence Greenhill, M.D., a psychiatrist at New York State
Psychiatric Institute and lead investigator of this multi-center study.
The primary efficacy measure was the difference from baseline on the
teacher's version of the Conners' Global Index (CGI). The CGI assesses
10 different levels of behavior and monitors treatment effectiveness and
changes over time. This measurement was completed in the morning and
afternoon during the last week of treatment. The estimated mean improvement
from baseline on the teacher's CGI was 7.9 for methylphenidate modified
release capsules compared to 1.2 for placebo (p less than .001).
Additionally, specific comparative analysis showed improvement versus placebo
was equally good in the morning and afternoon (p less than .001).
In the study, once daily methylphenidate modified release capsules had a
safety profile similar to other methylphenidate products. The most common
adverse events compared to placebo were headache, abdominal pain, anorexia,
Facts About ADHD
- -- Attention Deficit Hyperactivity Disorder (ADHD) is a behavioral
disorder with symptoms that include developmentally inappropriate
levels of attention, concentration, activity, distractibility and
impulsivity.(1) It is one of the most common psychiatric disorders of
childhood and adolescence and often persists into adulthood.(2)
- -- ADHD affects approximately three to five percent of school-aged
- -- ADHD has been shown to have long-term adverse effects on academic
performance, vocational success and social-emotional development.(1)
Medeva Pharmaceuticals, Inc. is the pharmaceutical marketing arm of
UK-based Celltech Group, an international R&D leader in antibody technology
with extensive medicinal chemistry as well as biopharmaceutical development
expertise. Medeva's U.S. operations are headquartered in Rochester, NY.
Medeva develops, manufactures, and markets prescription pharmaceuticals
worldwide. Areas of therapeutic focus include ADHD; liquid extended release
cough and cold products; diuretics for edema due to congestive heart failure
and hypertension; and a variety of niche products in allergy, respiratory,
weight loss and bladder cancer.
Eurand is an independent, multinational, oral drug delivery company
dedicated to providing the pharmaceutical industry with solutions to the most
challenging drug delivery problems. Eurand's extensive portfolio of
proprietary technologies provides a number of options to improve the
therapeutic performance of drugs and includes systems designed for enhanced
bioavailability, rapid onset of action, improved absorption, oral peptide
delivery, customized release, region specific drug delivery, taste masking and
quick dissolving formulations. Eurand has recently launched its newest
technology, Biorise, which is designed to enhance the bioavailability and
improve the onset of action of poorly soluble drugs. Eurand is a fully
integrated drug delivery company offering a complete range of development,
scale up and commercial manufacturing capabilities in both Europe and the USA.
- (1) Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder.
NIH Consens Statement 1998 Nov. 16-18; 16(2) p 3, 4, 8: In press.
- (2) Dulcan, M. Practice parameters for the assessment and treatment of
children, adolescents, and adults with
attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc
Psychiatry 1997; 36;10: 101S.
- (3) Diagnostic and Statistical Manual of Mental Disorders, 4th ed.
DSM-IV. Washington, D.C.: American Psychiatric Association, 1994,