An Effectiveness and Safety Study Evaluating OROS Methylphenidate Hydrochloride (HCl), Ritalin (Methylphenidate HCl) and Placebo in Children With Attention Deficit Hyperactivity Disorder - Full Text View

Purpose

The purpose of this study is to provide data on the effectiveness of the OROS Methylphenidate Hydrochloride (HCl) formulation compared to placebo and standard immediate-release Ritalin with respect to improving attention and behavior, and decreasing hyperactivity in children with Attention Deficit Hyperactivity Disorder (ADHD). Both OROS Methylphenidate HCl and Ritalin contain the central nervous system stimulant, methylphenidate HCl. The safety associated with the two methylphenidate formulations will also be compared with placebo.

Condition	Intervention	Phase
Attention Deficit Hyperactivity Disorder	Drug: Placebo Drug: OROS (methylphenidate HCl) Drug: Ritalin (methylphenidate)	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Screening, Efficacy, and Safety Study Evaluating OROS (Methylphenidate HCl), Ritalin and Placebo in Children With ADHD

Resource links provided by NLM:

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder

Drug Information available for: Methylphenidate Methylphenidate hydrochloride

U.S. FDA Resources

Further study details as provided by Alza Corporation, DE, USA:

Primary Outcome Measures:

IOWA Conners Inattention/Overactivity subscale ratings by the Community School Teacher [ Time Frame: Up to Day 6 of each treatment period for a total of approximatly 18 days ]

Secondary Outcome Measures:

SKAMP attention and deportment ratings [ Time Frame: Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days ]
Peer interaction ratings [ Time Frame: Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days ]
Laboratory School Teacher Global Assessments [ Time Frame: Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days ]
SNAP-IV ratings [ Time Frame: Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days ]
Incidence of adverse events [ Time Frame: Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days ]


Study Start Date:	November 1998
Study Completion Date:	January 1999

Arms	Assigned Interventions
Experimental: 001 OROS (methylphenidate HCl) Treatment A: 1 2 or 3 OROS methylphenidate 18-mg tablets + 0 1 or 2 OROS placebo tablets (3 tablets in total) once daily + 1 placebo capsule 3x/day for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A B and C.	Drug: OROS (methylphenidate HCl) Treatment A: 1, 2, or 3 OROS methylphenidate 18-mg tablets + 0, 1, or 2 OROS placebo tablets (3 tablets in total) once daily + 1 placebo capsule 3x/day for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A, B, and C.
Experimental: 002 Ritalin (methylphenidate) Treatment B: 5 10 or 15-mg tablets (encapsulated/single capsule) 3 times a day + 3 OROS placebo tablets once daily for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A B and C.	Drug: Ritalin (methylphenidate) Treatment B: 5, 10, or 15-mg tablets (encapsulated/single capsule) 3 times a day + 3 OROS placebo tablets once daily for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A, B, and C.
Experimental: 003 Placebo Treatment C: Three OROS placebo tablets once daily + 1 placebo capsule 3x times/day for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A B and C.	Drug: Placebo Treatment C: Three OROS placebo tablets once daily + 1 placebo capsule 3x times/day for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A, B, and C.

Detailed Description:

Attention Deficit Hyperactivity Disorder (ADHD) represents the most common neurobehavioral disorder in children, affecting 3% to 5% of the school-age population. Behavioral pediatricians, child psychiatrists, and child neurologists indicate that referrals for ADHD may constitute up to 50% of their practices. This is a double-blind, double-dummy, randomized, placebo-controlled, active-controlled, 3-treatment, 3-period crossover trial to compare the safety and effectiveness (onset of effect, time to loss of effect and overall efficacy) of OROS Methylphenidate Hydrochloride (HCl), with standard immediate-release Ritalin and placebo. During this study, patients receive each of the three treatments (OROS Methylphenidate HCl 18, 36 or 54 milligrams per day, Ritalin 5, 10 or 15 milligrams three times per day, or placebo) for 7 days, and are assigned to one of three dosage levels depending upon their prestudy methylphenidate dose and regimen. The total study participation for each patient will be 21 days. Since ADHD is manifested in a variety of settings and can affect attention and behavior, this study assesses efficacy in home, community school, and laboratory school settings using numerous assessments designed to evaluate various aspects of the disorder. These assessments are completed by a variety of raters, including the parents/caregivers, community school teachers, and laboratory school teachers. The primary measure of effectiveness is the community school teacher's rating on the IOWA Conners Inattention/Overactivity subscale. Additional measures of effectiveness include the IOWA Conners (Inattention/Overactivity and Oppositional/Defiance subscale) ratings, SKAMP attention and deportment ratings, peer interaction and other behavioral ratings, global assessments, SNAP-IV ratings, activity levels during structured activities, accuracy and productivity of independent assigned academic seatwork, and a home situation questionnaire. Safety evaluations include the incidence of adverse events, physical examinations, clinical laboratory tests, vital signs, sleep quality, actigraphy (sleep latency, duration, and arousals), appetite, and the presence/severity of tics (hard-to-control, repeated twitching of any parts of the body or hard-to-control repeating of sounds or words). Patients will be given oral doses of: OROS (methylphenidate HCl) 1, 2, or 3 of the 18-milligram tablets once daily, or Ritalin 5, 10, or 15 mg (encapsulated/single capsule) three times a day, or placebo. There are three treatment groups, each group dosing for 7 days for a total of 21 days on study.

Eligibility


Ages Eligible for Study:	6 Years to 12 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients having a diagnosis of one of the three subtypes of Attention Deficit Hyperactivity Disorder (ADHD) verified by both a parent/child interview and a teacher assessment using SNAP-IV questionnaires
taking or have taken in the past 5 - 20 mg of immediate-release methylphenidate (Ritalin) at least twice a day, 20 - 60 mg of sustained-release methylphenidate (Ritalin-SR) per day, or a combination of immediate-release and sustained-release methylphenidate up to a daily dose not exceeding 60 mg
having used methylphenidate for at least 3 months at some time in the past without any significant adverse experiences, considered to be positive responders to methylphenidate therapy, and agreeing to take to take only the supplied study drug as treatment for ADHD during the three-week treatment phase of the study
able to comply with the study visit schedule and whose parent(s) and teacher are willing and able to complete the protocol-specified assessments
agreeing not to ingest any caffeine containing beverages (e.g., coffee or soda) or foods (e.g., chocolate) on days 7, 14, and 21 of the study.

Exclusion Criteria:

Patients having clinically significant gastrointestinal problems, including narrowing of the gastrointestinal tract
having glaucoma, an ongoing seizure disorder, a psychotic disorder, or have a diagnosis of Tourette's syndrome
whose primary treatment focus is oppositional-defiant disorder, conduct disorder, or tics, or whose primary treatment focus is psychiatric conditions such as depressive disorders, bipolar disorders, or other mood disorders
having a mean of two blood pressure measurements (systolic or diastolic) equal to or greater than the 95th percentile for age, sex, and height at screening
if female, have begun menstruation.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00269776

Sponsors and Collaborators

Alza Corporation, DE, USA

Investigators


Study Director:	Alza Corporation Clinical Trial	ALZA

More Information

Publications:

Swanson J, Gupta S, Lam A, Shoulson I, Lerner M, Modi N, Lindemulder E, Wigal S. Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies. Arch Gen Psychiatry. 2003 Feb;60(2):204-11.


Responsible Party:	Director, Clinical Research - CNS, Johnson & Johnson Pharmaceutical Research and Development, L.L.C.
ClinicalTrials.gov Identifier:	NCT00269776 History of Changes
Other Study ID Numbers:	CR005989 CONCERTAATT3019 C-98-003-02
Study First Received:	December 22, 2005
Last Updated:	July 8, 2011

Keywords provided by Alza Corporation, DE, USA:


ADHD Attention Deficit Hyperactivity Disorder OROS	children methylphenidate Ritalin

Additional relevant MeSH terms:


Attention Deficit Disorder with Hyperactivity Hyperkinesis Attention Deficit and Disruptive Behavior Disorders Neurodevelopmental Disorders Mental Disorders Dyskinesias Neurologic Manifestations Nervous System Diseases Signs and Symptoms	Methylphenidate Central Nervous System Stimulants Physiological Effects of Drugs Dopamine Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Dopamine Agents Neurotransmitter Agents

ClinicalTrials.gov processed this record on June 23, 2017